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Islet transplantation has been developed as an effective cell therapy strategy to treat the progressive life-threatening disease Type 1 diabetes (T1DM). To mimic the natural islets and achieve immune isolation, hydrogel encapsulation of multiple islet cell types is the current endeavor. Here, we present a microfiber loading with pancreatic α and β cells by microfluidic spinning for diabetes treatment. Benefiting from microfluidic technology, the cells could be controllably and continuously loaded in the alginate and methacrylated hyaluronic acid (Alg-HAMA) microfiber and maintained their high bioactivity. The resultant microfiber could then hold the capacity of dual-mode glucose responsiveness attributed to the glucagon and insulin secreted by the encapsulated pancreatic α and β cells. After transplantation into the brown adipose tissue (BAT), these cell-laden microfibers showed successful blood glucose control in rodents and avoided the occurrence of hypoglycemia. These results conceived that the multicellular microfibers are expected to provide new insight into artificial islet preparation, diabetes treatment, and regenerative medicine as well as tissue engineering. • The microfibers were generated with a double network of alginate and methacrylated hyaluronic acid. • The microfibers could simultaneously encapsulate pancreatic α and β cells and showed dual-mode glucose responsiveness. • The cell-laden microfibers maintained a long-term hormone-releasing function in vivo. • Cell-laden microfibers transplanted into diabetic mice could achieve glycemic control for 6 weeks. [Display omitted] [ABSTRACT FROM AUTHOR]

Objective: This systematic review evaluates the efficacy of buccal pad fat (BPF) as an autologous graft in the treatment of gingival recession (GR). Thus, the research question explores if the BPF can serve as a viable alternative to the gold standard connective tissue graft. Materials and methods: Only seven studies met the inclusion criteria were critically appraised including the randomized controlled clinical trials, and case series. The inclusion criteria were systemically healthy individuals in the age range (18–65 years old) with Miller's classification of GR either class I, II, III, or IV while exclusion criteria were patients with poor oral hygiene, pregnant and lactating patients, teeth with caries, any prior surgery in the relevant regions, and use of medications. Results: The review included 117 patients with 136 GR defects. The age of participants ranges from 20 to 65 years old with the higher percentage of root coverage (%RC) at 6 months in the pedicled BPF group which was 89.30%while the lowest (%RC) at 6 months in the same group was 46.78%. The BPF group's width of keratinized gingiva (WKG) values indicate a notable improvement, suggesting a positive impact on WKG compared to the control group. Conclusions: BPF can be considered as a promising graft to augment gingival tissues at different sites in the oral cavity with different Miller's classes of GR providing a new era in GR treatment. [ABSTRACT FROM AUTHOR]

Objectives: We evaluated the closure rate after fat-graft myringoplasty (FGM) of perforations differing in size and location. We explored whether patient's factors and the FGM surgical technique influenced surgical outcomes. Methods: We retrospectively studied patients with tympanic membrane perforations who underwent FGM from March 2015 to March 2019. All procedures were performed by a single senior surgeon at our tertiary hospital. The patients who followed-up for at least 6 months after surgery were enrolled. We recorded hypertension and diabetes status, age, any prior ear surgery, any calcific plaques adjacent to the perforation, and perforation size and location. Results: A total of 150 patients were enrolled. Our success rate of FGM was 90%. Hypertension, diabetes, prior ear surgery history, and eardrum calcific plaques did not affect the surgical outcomes. There was no statistical difference in the surgical success rate according to the size (< 50%) or location of perforation. The closure rate was 97.2% in patients aged 1660 and 87.5% in patients aged > 60, respectively. However, FGM was successful in only two of six children (33.3%) aged ≤ 15 years, thus significantly less than in the other groups. Conclusion: FGM is a fast, safe, and efficient method for repairing tympanic membrane perforation. The surgical outcome is not significantly affected by underlying disease, perforation size or location, or by the condition of the tympanic membrane or older age. However, it may be poor in children with dysfunctional Eustachian tube. [ABSTRACT FROM AUTHOR]

Obesity is a complex medical condition caused by a positive imbalance between calorie intake and calorie consumption. Brown adipose tissue (BAT), along with the newly discovered "brown-like" adipocytes (called beige cells), functions as a promising therapeutic tool to ameliorate obesity and metabolic disorders by burning out extra nutrients in the form of heat. Many studies in animal models and humans have proved the feasibility of this concept. In this review, we aim to summarize the endeavors over the last decade to achieve a higher number/activity of these heat-generating adipocytes. In particular, pharmacological compounds, especially agonists to the β3 adrenergic receptor (β3-AR), are reviewed in terms of their feasibility and efficacy in elevating BAT function and improving metabolic parameters in human subjects. Alternatively, allograft transplantation of BAT and the transplantation of functional brown or beige adipocytes from mesenchymal stromal cells or human induced pluripotent stem cells (hiPSCs) make it possible to increase the number of these beneficial adipocytes in patients. However, practical and ethical issues still need to be considered before the therapy can eventually be applied in the clinical setting. This review provides insights and guidance on brown- and beige-cell-based strategies for the management of obesity and its associated metabolic comorbidities. [ABSTRACT FROM AUTHOR]

Transplantation of brown adipose tissue (BAT) is a promising approach for treating obesity and metabolic disorders. However, obtaining sufficient amounts of functional BAT or brown adipocytes for transplantation remains a major challenge. In this study, we developed a hydrogel that combining adipose acellular matrix (AAM) and GelMA and HAMA that can be adjusted for stiffness by modulating the duration of light‐crosslinking. We used human white adipose tissue‐derived microvascular fragments to create beige adipose organoids (BAO) that were encapsulated in either a soft or stiff AAM hydrogel. We found that BAOs cultivated in AAM hydrogels with high stiffness demonstrated increased metabolic activity and upregulation of thermogenesis‐related genes. When transplanted into obese and type 2 diabetes mice, the HFD + BAO group showed sustained improvements in metabolic rate, resulting in significant weight loss and decreased blood glucose levels. Furthermore, the mice showed a marked reduction in nonalcoholic liver steatosis, indicating improved liver function. In contrast, transplantation of 2D‐cultured beige adipocytes failed to produce these beneficial effects. Our findings demonstrate the feasibility of fabricating beige adipose organoids in vitro and administering them by injection, which may represent a promising therapeutic approach for obesity and diabetes. [ABSTRACT FROM AUTHOR]

Summary: The induction of thermogenesis in brown adipose tissue is emerging as an attractive therapy for obesity and metabolic syndrome. However, the long‐term efficacy and safety of clinical pharmaceutical agents have yet to be fully characterized. The transplantation of brown adipose tissue represents an alternative approach that might have a therapeutic effect by inducing a long‐term increase in energy expenditure. However, limited tissue resources hinder the development of transplantation. Stem cell‐based therapy and brown adipose tissue engineering, in addition to transplantation, represent alternative approaches that might resolve this problem. In this article, we discuss recent advances in understanding the mechanisms and applications of brown adipose tissue transplantation in the treatment of obesity and related metabolic disorders. Specifically, the induction of brown adipocytes and the fabrication of engineered brown adipose tissue as novel transplantation resources have long‐term effects on ameliorating metabolic defects in rodent models. Additionally, we explore future prospects regarding the development of three‐dimensional engineered brown adipose tissue and the associated challenges. [ABSTRACT FROM AUTHOR]

Physical activity is increasingly recommended as a therapeutic approach for various lifestyle-related conditions, including type 2 diabetes, dementia, cardiovascular diseases, and cancer. Recent advancements in scientific research have uncovered the role of skeletal muscle as an endocrine organ, releasing interleukin 6 (IL-6) in response to physical activity. This secretion facilitates communication between the muscle and other organs/systems in the body, including the brain, adipose tissue, brown tissue, bone, liver, gut, pancreas, and within the muscle itself. IL-6 has diverse biological functions, including appetite regulation, lipid and glucose metabolism, promotion of browning of white adipose tissue, bone formation, muscle hypertrophy, and modulation of tumor growth. A search was conducted in PubMed and Web of Science from inception until December 2022 to identify original studies investigating the cross-talk mediated by Interleukin 6 during exercise. These findings suggest that IL-6 could serve as a valuable biomarker to monitor exercise prescription for individuals with conditions, such as cancer, diabetes, cardiovascular diseases, and neurodegenerative disorders. [ABSTRACT FROM AUTHOR]

Development of osteochondral tissue engineering approaches using scaffolds seeded with stem cells in association with mechanical stimulations has been recently considered as a promising technique for the repair of this tissue. In this study, an integrated and biomimetic trilayered silk fibroin (SF) scaffold containing SF nanofibers in each layer was fabricated. The osteogenesis and chondrogenesis of stem cells seeded on the fabricated scaffolds were investigated under a perfusion flow. 3‐Dimethylthiazol‐2,5‐diphenyltetrazolium bromide assay showed that the perfusion flow significantly enhanced cell viability and proliferation. Analysis of gene expression by stem cells revealed that perfusion flow had significantly upregulated the expression of osteogenic and chondrogenic genes in the bone and cartilage layers and downregulated the hypertrophic gene expression in the intermediate layer of the scaffold. In conclusion, applying flow perfusion on the prepared integrated trilayered SF‐based scaffold can support osteogenic and chondrogenic differentiation for repairing osteochondral defects. [ABSTRACT FROM AUTHOR]

Objective(s): Bone tissue engineering is considered a new method in the treatment of bone defects and can be an effective alternative to surgery and bone grafting. The use of adipose tissue mesenchymal stem cells (ADMSCs) on synthetic polymer scaffolds is one of the new approaches in bone tissue engineering. In this study, we aimed to investigate the effect of laminin coating on biocompatibility and osteogenic differentiation of ADMSCs seeded on polycaprolactone (PCL) scaffolds. Materials and Methods: The morphology of the electrospun scaffold was evaluated using a scanning electron microscope (SEM). Cell proliferation and cytotoxicity were determined by MTT assay. The adipogenic and osteogenic differentiation potential of the cells was evaluated. The osteogenic differentiation of ADMSCs cultured on the PCL scaffold coated with laminin was assessed by evaluating the level of alkaline phosphatase (ALP) activity, intracellular calcium content, and expression of bone-specific genes. Results: The results showed that the ADMSCs cultured on PCL/laminin showed enhanced osteogenic differentiation compared to those cultured on non-coated PCL or control medium (P<0.05). Conclusion: It seems that laminin enhances the physicochemical properties and biocompatibility of PCL nanofiber scaffolds; and by modifying the surface of the scaffold, improves the differentiation of ADMSCs into osteogenic cells. [ABSTRACT FROM AUTHOR]

Background: Various stimulation methods, including electrical, ultrasound, mechanical, and biological interventions, are explored, each leveraging intricate cellular and molecular dynamics to expedite healing. The advent of stromal vascular fraction (SVF) marks a significant stride, offering multifarious benefits in bone healing, from enhanced bone formation to optimal vascular integration, drawing a harmonious balance between innate mechanisms and scientific advancements. Methods: This systematic review was conducted focusing on literature from 2016 to 2023 and encompassing various bone healing stimulation mechanisms like SVF, electrical, ultrasound, and mechanical stimulation. The extracted data underwent meticulous synthesis and analysis, emphasizing comparative evaluations of mechanisms, applications, and outcomes of each intervention. Results: The reviewed studies reveal the potential of SVF in bone fracture healing, with its regenerative and anti-inflammatory effects. The purification of SVF is crucial for safe therapeutic use. Characterization involves flow cytometry and microscopy. Studies show SVF's efficacy in bone regeneration, versatility in various contexts, and potential for clinical use. SVF appears superior to electrical, ultrasound, and mechanical stimulation, with low complications. Conclusions: This review compares bone healing methods, including SVF. It provides valuable insights into SVF's potential for bone regeneration. However, due to limited human studies and potential bias, cautious interpretation is necessary. Further research is essential to validate these findings and determine the optimal SVF applications in bone healing. [ABSTRACT FROM AUTHOR]

This article discusses a rare disorder called Barraquer-Simons syndrome, also known as acquired partial lipodystrophy (APL). The syndrome involves the loss of subcutaneous fat from certain areas of the body, such as the face, arms, and upper trunk, while the lower trunk and legs may have normal or increased fat. The article presents a case study of a 36-year-old male who experienced progressive hollowing of the shoulder and chest since the age of 14, along with muscle pain. The patient was diagnosed with Barraquer-Simons syndrome associated with myopathy, which is a rare occurrence. The exact cause and treatment of APL are still unknown, but various treatments have been attempted. [Extracted from the article]

Summary: Because lipofilling is often associated with various reconstructive procedures, especially breast reconstructions, improving fat-graft retention remains a major concern for plastic surgeons. We conducted an experimental protocol in a rat model simulating an autologous breast reconstruction method using the fat-augmented latissimus dorsi myocutaneous (LDM) flap. This study aimed to compare the survival rates of autologous adipocytes when injected subcutaneously and intramuscularly and to evaluate the role of recipient host tissue, volume of the injected fat, and postoperative radiation on fat-graft retention.Thirty rats were divided into five groups (A, B, C, D, and E), of six rats each. All animals underwent a pedicled LDM flap transfer to the anterior thoracic wall, and different volumes of autologous fat were injected into three recipient areas, namely, the pectoralis major and latissimus dorsi muscles and the subcutaneous tissue of the flap's skin island, as follows: 1 mL of fat was injected in total in group A, 2 mL in groups B and D, and 5 mL in group C. Group D animals received postoperative radiation (24 Gy), whereas group E animals (controls) did not undergo any fat grafting procedure. Eight weeks after surgery, adipocyte survival was assessed in all groups using histological and immunochemistry techniques.The results showed that the pectoralis major muscle was the substrate with the highest adipocyte survival rates, which were proportional to the amount of fat injected, followed by the latissimus dorsi muscle and the subcutaneous tissue. Increased volumes of transplanted fat into the subcutaneous tissue did not correspond to increased adipocyte survival. Irradiation of host tissues resulted in a statistically significant decrease in surviving adipocytes in all three recipient sites (p

Purpose: To describe the benefits of covering the extrasinusal length of extramaxillary zygomatic implants with a pedicled buccal fat pad flap through a tunnel approach. Materials and Methods: Four extramaxillary zygomatic implants were placed in 10 patients and loaded immediately with an acrylic provisional fixed prosthesis. The extrasinusal length of every implant was covered with a pedicled buccal fat pad flap. Study variables were implant survival rate, peri-implant soft tissue recession (PISTR), peri-implant soft tissue condition (PISTC), modified Bleeding Index (mBI), and suppuration. The statistical analysis comprised the Brunner-Langer model of longitudinal data for each variable and the analysis of variance to assess main effects and interactions. Results: All the zygomatic implants showed osseointegration, resulting in a survival rate of 100%. The PISTR was evaluated after surgery (T0) and after 12 months (T1), statistically significant differences being observed (P = .014). Recession also depended on specific implant positioning; zygomatic implants in the anterior were found to have a higher risk of recession vs implants in the posterior (P = .065). The PISTC was assessed at T0 and T1, and no statistically significant changes were observed (P = .718). Bleeding on probing was present in 10% of the implants at T0 and in 15% at T1, the difference being nonsignificant (P = .317). Conclusion: The use of a pedicled buccal fat pad flap to cover the extrasinusal length of extramaxillary zygomatic implants appears to reduce the risk of soft tissue recession and exposure of the implant surface to the oral cavity. [ABSTRACT FROM AUTHOR]

Traumatic spinal cord injuries (SCIs) often result in sensory, motor, and vegetative function loss below the injury site. Although preclinical results have been promising, significant solutions for SCI patients have not been achieved through translating repair strategies to clinical trials. In this study, we investigated the effective potential of mechanically activated lipoaspirated adipose tissue when transplanted into the epicenter of a thoracic spinal contusion. Male Sprague Dawley rats were divided into three experimental groups: SHAM (uninjured and untreated), NaCl (spinal cord contusion with NaCl application), and AF (spinal cord contusion with transplanted activated human fat). Pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) were measured to assess endogenous inflammation levels 14 days after injury. Sensorimotor recovery was monitored weekly for 12 weeks, and gait and electrophysiological analyses were performed at the end of this observational period. The results indicated that AF reduced endogenous inflammation post-SCI and there was a significant improvement in sensorimotor recovery. Moreover, activated adipose tissue also reinstated the segmental sensorimotor loop and the communication between supra- and sub-lesional spinal cord regions. This investigation highlights the efficacy of activated adipose tissue grafting in acute SCI, suggesting it is a promising therapeutic approach for spinal cord repair after traumatic contusion in humans. [ABSTRACT FROM AUTHOR]

Stem cell therapy is a promising treatment in regenerative medicine. Human adipose-derived stem/stromal cells (hASCs), a type of mesenchymal stem cell, are easy to harvest. In plastic and aesthetic surgery, hASC may be applied in the treatment of fat grafting, wound healing, and scar remodeling. Platelet-rich plasma (PRP) contains various growth factors, including platelet-derived growth factor (PDGF), which accelerates wound healing. We previously reported that PRP promotes the proliferation of hASC via multiple signaling pathways, and we evaluated the effect of PRP on the stimulation of hASC adhesion and migration, leading to the proliferation of these cells. When hASCs were treated with PRP, AKT, ERK1/2, paxillin and RhoA were rapidly activated. PRP treatment led to the formation of F-actin stress fibers. Strong signals for integrin β1, paxillin and RhoA at the cell periphery of RPR-treated cells indicated focal adhesion. PRP promoted cell adhesion and movement of hASC, compared with the control group. Imatinib, an inhibitor of the PDGF receptor tyrosine kinase, inhibited the promotion of PRP-dependent cell migration. PDGF treatment of hASCs also stimulated cell adhesion and migration but to a lesser extent than PRP treatment. PRP promoted the adhesion and the migration of hASC, mediated by the activation of AKT in the integrin signaling pathway. PRP treatment was more effective than PDGF treatment in enhancing cell migration. Thus, the ability of PRPs to promote migration of hASC to enhance cell growth is evident. [ABSTRACT FROM AUTHOR]

Absence of leptin confers metabolic dysfunction resulting in morbid obesity. Bone growth and maturation are also impaired. Partial leptin resistance is more common than leptin deficiency and, when induced by feeding mice a high fat diet, often has a negative effect on bone. Here, we used a genetic model to invest igate the skeletal effects of partial and total leptin resistance in mice. This was accomplished by comparing the skeletal phenotypes of 17-week-old female C57Bl6/J wild-type (WT) mice, partial leptin receptor-deficient (db/+) mice and leptin receptor-deficient (db/db) mice (n = 7-8/group), all fed a standard diet. Compared to WT mice, db/db mice were dramatically heavier and hyperleptinemic. These mice were also hypogonadal, hyperglycemic, osteopenic and had lower serum levels of bone turnover markers, osteocalcin and C-terminal telopeptide of type I collagen (CTX). Compared to WT mice, db/+ mice were 14% heavier, had 149% more abdominal white adipose tissue, and were mildly hyperglycemic. db/+ mice did not differ from WT mice in uterine weight or serum levels of mar kers of bone turnover, although there was a trend for lower osteocalcin. At the bone microarchitectural level, db/+ mice differed from WT mice in having more massive femurs and a trend (P = 0.072) for larger vertebrae. These findings suggest that db/+ mice fed a normal mouse diet compensate for partial leptin resistance by increasing white adipose tissue mass which results in higher leptin levels. Our findings suggest that db/+ mice are a useful dietindependent model for studying the effects of partial leptin res istance on the skeleton. [ABSTRACT FROM AUTHOR]

Subchondral bone cysts in horses represent one of the main causes of lameness that can occur in different anatomical locations. The study describes the treatment in regenerative therapy of the intracystic implantation of adipose tissue mesenchymal stromal cells (AMSCs) included in platelet-rich plasma (PRP). The ability of AMSCs to differentiate in osteogenic cells was tested in vitro and in vivo. Given the aim to investigate the application of AMSCs in bone defects and orthopedic pathologies in horses, a four-year-old male thoroughbred racing horse that had never raced before was treated for lameness of the left hind leg caused by a cyst of the medial femoral condyle. The horse underwent a new surgery performed with an arthroscopic approach in which the cystic cavity was filled with AMSCs contained in the PRP. Radiographs were taken 3, 5, and 10 months after the surgery to assess the development of newly regenerated bone tissue in the gap left by the cyst. Twelve months after the operation and after six months of regular daily training, the horse did not show any symptoms of lameness and started a racing career. According to the study, the use of AMSCs and PRP suggests promising benefits for treating subchondral bone cysts. [ABSTRACT FROM AUTHOR]

Abstract Background Lipodystrophy-associated metabolic disorders caused by Seipin deficiency lead to not only severe lipodystrophy but also neurological disorders. However, the underlying mechanism of Seipin deficiency-induced neuropathy is not well elucidated, and the possible restorative strategy needs to be explored. Methods In the present study, we used Seipin knockout (KO) mice, combined with transcriptome analysis, mass spectrometry imaging, neurobehavior test, and cellular and molecular assay to investigate the systemic lipid metabolic abnormalities in lipodystrophic mice model and their effects on adult neurogenesis in the subventricular zone (SVZ) and olfactory function. After subcutaneous adipose tissue (AT) transplantation, metabolic and neurological function was measured in Seipin KO mice to clarify whether restoring lipid metabolic homeostasis would improve neurobehavior. Results It was found that Seipin KO mice presented the ectopic accumulation of lipids in the lateral ventricle, accompanied by decreased neurogenesis in adult SVZ, diminished new neuron formation in the olfactory bulb, and impaired olfactory-related memory. Transcriptome analysis showed that the differentially expressed genes (DEGs) in SVZ of adult Seipin KO mice were significantly enriched in lipid metabolism. Mass spectrometry imaging showed that the levels of glycerophospholipid and diglyceride (DG) were significantly increased. Furthermore, we found that AT transplantation rescued the abnormality of peripheral metabolism in Seipin KO mice and ameliorated the ectopic lipid accumulation, concomitant with restoration of the SVZ neurogenesis and olfactory function. Mechanistically, PKCα expression was up-regulated in SVZ tissues of Seipin KO mice, which may be a potential mediator between lipid dysregulation and neurological disorder. DG analogue (Dic8) can up-regulate PKCα and inhibit the proliferation and differentiation of neural stem cells (NSCs) in vitro, while PKCα inhibitor can block this effect. Conclusion This study demonstrates that Seipin deficiency can lead to systemic lipid disorder with concomitant SVZ neurogenesis and impaired olfactory memory. However, AT restores lipid homeostasis and neurogenesis. PKCα is a key mediator mediating Seipin KO-induced abnormal lipid metabolism and impaired neurogenesis in the SVZ, and inhibition of PKCα can restore the impaired neurogenesis. This work reveals the underlying mechanism of Seipin deficiency-induced neurological dysfunction and provides new ideas for the treatment of neurological dysfunction caused by metabolic disorders.

Severe spinal cord injuries (SCIs) usually result in the temporary or permanent impairment of strength, sensation or autonomic functions below the sites of injuries. To date, a large number of therapeutic approaches have been used to ameliorate SCIs, and subsequent stem cell transplantation appears to be a promising strategy. The aim of this study was to evaluate the therapeutic effect of stem cells by changes in the evoked potentials at different time points after a transplantation of spermatogonial stem cells (SSCs) to differentiate the source neurons in a rat model with SCIs, as well as through histopathology. A modified Plemel spinal cord lateral compression model was used. The experiment was divided into a blank, a control and a SSC transplantation group. Motor activity scores, sensory evoked potentials (SEPs) and motor evoked potentials (MEPs) were assessed through motor resuscitation as well as histologic evaluation on each experimental group to determine the improvement. Consistent with our results, motor scores and evoked potentials were significantly improved in the SSC transplantation group. In addition, a histologic assessment showed that the transplanted stem cells had a significant restorative effect on the reconstruction of tissue cells. 1 week after the stem cell transplantation, the SSC transplantation group showed improvement in spinal cord functions and spinal cord pathologic injuries. After 2 weeks and beyond, the SSC transplantation group showed significant improvement in spinal cord functions and spinal cord pathology compared to the control group, meanwhile the evoked potentials and motor function of the hind limbs of rats in the SSC transplantation group were significantly improved. Therefore, the therapeutic strategies for spermatogonial stem cells will be an effective program in the study on SCIs, and we suggest the somatosensory evoked potentials as a tool to assess the degree of recovery from SCIs after the transplantation of stem cells. [ABSTRACT FROM AUTHOR]

Objective: Fat injection laryngoplasty (FIL) is a common procedure used to correct glottic insufficiency. Nevertheless, few studies have discussed potential treatments for cases with poor voice recovery after FIL. Methods: Eighteen patients with unfavorable vocal outcomes from FIL were analyzed. Each of these patients presented persistent dysphonia for more than 2 months following FIL, together with bulging vocal folds and poor mucosal wave. We applied microsurgery as the standard treatment to remove excessive fat. Vocal fold steroid injection (VFSI) was administered to patients that were hesitant or declined to undergo microsurgery. Voice outcomes were evaluated using the Voice Handicap Index-10 (VHI-10), grade-roughness-breathiness (GRB) scores, and smoothed cepstral peak prominence (CPPs). Results: Six patients underwent microsurgery directly, 6 patients received only VFSIs as a salvage treatment, and the remaining 6 patients received 1 to 3 courses of VFSIs before the decision to undergo microsurgery. Pathology reports were available for 10 patients, and contained 5 instances of adipose tissues, 3 of fat necrosis, 1 of chronic inflammation, and 1 of fibrosis. Seventeen patients reported satisfactory or improved outcomes. We found remarkable improvements in VHI-10, GRB, and CPPs (all P <.05) after salvage treatments for FIL. Subgroup analyses showed comparable voice outcomes for patients undergoing direct microsurgery, VFSI alone, and VFSI followed by microsurgery (P >.05). Conclusions: This study demonstrated that fat overinjection and/or fibrotic change in the injected vocal folds may cause poor voice outcomes after FIL. Both microsurgery and VFSI could be applied as salvage treatments with good voice recovery profiles. Level of evidence: Level 4. [ABSTRACT FROM AUTHOR]

Negative regulation of exocytosis from secretory cells is accomplished through inhibitory signals from Gi/o GPCRs by Gβγ subunit inhibition of 2 mechanisms: decreased calcium entry and direct interaction of Gβγ with soluble N-ethylmaleimide– sensitive factor attachment protein (SNAP) receptor (SNARE) plasma membrane fusion machinery. Previously, we disabled the second mechanism with a SNAP25 truncation (SNAP25Δ3) that decreased Gβγ affinity for the SNARE complex, leaving exocytotic fusion and modulation of calcium entry intact and removing GPCR-Gβγ inhibition of SNARE-mediated exocytosis. Here, we report substantial metabolic benefit in mice carrying this mutation. Snap25Δ3/Δ3 mice exhibited enhanced insulin sensitivity and beiging of white fat. Metabolic protection was amplified in Snap25Δ3/Δ3 mice challenged with a high-fat diet. Glucose homeostasis, whole-body insulin action, and insulin-mediated glucose uptake into white adipose tissue were improved along with resistance to diet-induced obesity. Metabolic protection in Snap25Δ3/Δ3 mice occurred without compromising the physiological response to fasting or cold. All metabolic phenotypes were reversed at thermoneutrality, suggesting that basal autonomic activity was required. Direct electrode stimulation of sympathetic neuron exocytosis from Snap25Δ3/Δ3 inguinal adipose depots resulted in enhanced and prolonged norepinephrine release. Thus, the Gβγ-SNARE interaction represents a cellular mechanism that deserves further exploration as an additional avenue for combating metabolic disease. [ABSTRACT FROM AUTHOR]

Background: Lipodystrophy-associated metabolic disorders caused by Seipin deficiency lead to not only severe lipodystrophy but also neurological disorders. However, the underlying mechanism of Seipin deficiency-induced neuropathy is not well elucidated, and the possible restorative strategy needs to be explored. Methods: In the present study, we used Seipin knockout (KO) mice, combined with transcriptome analysis, mass spectrometry imaging, neurobehavior test, and cellular and molecular assay to investigate the systemic lipid metabolic abnormalities in lipodystrophic mice model and their effects on adult neurogenesis in the subventricular zone (SVZ) and olfactory function. After subcutaneous adipose tissue (AT) transplantation, metabolic and neurological function was measured in Seipin KO mice to clarify whether restoring lipid metabolic homeostasis would improve neurobehavior. Results: It was found that Seipin KO mice presented the ectopic accumulation of lipids in the lateral ventricle, accompanied by decreased neurogenesis in adult SVZ, diminished new neuron formation in the olfactory bulb, and impaired olfactory-related memory. Transcriptome analysis showed that the differentially expressed genes (DEGs) in SVZ of adult Seipin KO mice were significantly enriched in lipid metabolism. Mass spectrometry imaging showed that the levels of glycerophospholipid and diglyceride (DG) were significantly increased. Furthermore, we found that AT transplantation rescued the abnormality of peripheral metabolism in Seipin KO mice and ameliorated the ectopic lipid accumulation, concomitant with restoration of the SVZ neurogenesis and olfactory function. Mechanistically, PKCα expression was up-regulated in SVZ tissues of Seipin KO mice, which may be a potential mediator between lipid dysregulation and neurological disorder. DG analogue (Dic8) can up-regulate PKCα and inhibit the proliferation and differentiation of neural stem cells (NSCs) in vitro, while PKCα inhibitor can block this effect. Conclusion: This study demonstrates that Seipin deficiency can lead to systemic lipid disorder with concomitant SVZ neurogenesis and impaired olfactory memory. However, AT restores lipid homeostasis and neurogenesis. PKCα is a key mediator mediating Seipin KO-induced abnormal lipid metabolism and impaired neurogenesis in the SVZ, and inhibition of PKCα can restore the impaired neurogenesis. This work reveals the underlying mechanism of Seipin deficiency-induced neurological dysfunction and provides new ideas for the treatment of neurological dysfunction caused by metabolic disorders. [ABSTRACT FROM AUTHOR]

Objective: This study was designed to analyze the clinical effect of autologous fat-granule transplantation in augmentation rhinoplasty and explore methods to improve the fat retention rate. Methods: A total of 70 enrolled patients were randomly divided into 2 groups: the platelet-rich fibrin (PRF) combined with high-density fat transplantation group (combined group) and the conventional fat-granule transplantation group (control group; n = 35 in each group). In the combined group, an appropriate amount of autologous fat was extracted and centrifuged, and the lower layer of high-density fat was taken and mixed with PRF isolated from whole blood for autotransplantation. In the control group, only fat was extracted and centrifuged for transplantation. The patients were followed up with for more than one year to observe the short- and long-term effects, complications, safety, and patient satisfaction. Results: Six months after the operation, the nasal shape was stable, the contour was higher and more stereoscopic than before, the average increase of nasal height was 3.0 mm in the combined group and 2.0 mm in the control group. No complications, such as fat embolism, infection, or necrosis occurred during the 1-year follow-up. The satisfaction rate between the 2 groups has statistical significance (P <.05). Conclusion: Overall, PRF combined with autologous high-density fat transplantation is simple to perform, has a significantly increased fat-retention rate than the control group, and has stable long-term effects without obvious adverse reactions. A sufficient amount of fat and PRF transplantation can achieve a good orthopedic effect. Thus, this method can be widely used in clinical augmentation rhinoplasty. [ABSTRACT FROM AUTHOR]

Alveolar ridge augmentation is an important dental procedure to increase the volume of bone tissue in the alveolar ridge before the installation of a dental implant. To meet the high demand for bone grafts for alveolar ridge augmentation and to overcome the limitations of autogenous bone, allografts, and xenografts, researchers are developing bone grafts from synthetic materials using novel fabrication techniques such as 3D printing. To improve the clinical performance of synthetic bone grafts, stem cells with osteogenic differentiation capability can be loaded into the grafts. In this pilot study, we propose a novel bone graft which combines a 3D-printed polycaprolactone–tricalcium phosphate (PCL-TCP) scaffold with adipose-derived mesenchymal stem cells (AD-MSCs) that can be harvested, processed and implanted within the alveolar ridge augmentation surgery. We evaluated the novel bone graft in a porcine lateral alveolar defect model. Radiographic analysis revealed that the addition of AD-MSCs to the PCL-TCP scaffold improved the bone volume in the defect from 18.6% to 28.7% after 3 months of healing. Histological analysis showed the presence of AD-MSCs in the PCL-TCP scaffold led to better formation of new bone and less likelihood of fibrous encapsulation of the scaffold. Our pilot study demonstrated that the loading of AD-MSCs improved the bone regeneration capability of PCL-TCP scaffolds, and our novel bone graft is suitable for alveolar ridge augmentation. [ABSTRACT FROM AUTHOR]

The article offers information on the mechanisms of thermoregulation in mammals, focusing on the activation of bioenergetic processes, including shivering and nonshivering thermogenesis. Topics include the plasticity of adipose tissue, the potential for adipocyte thermogenesis as a therapeutic target for obesity and cardiometabolic diseases, and a turning point in 2008-2009 with breakthrough studies revealing the common ancestry of brown adipocytes and skeletal muscle cells.

Purpose: The purpose of this prospective randomized clinical trial is to compare the clinical outcomes of three injections of leucocyte-poor platelet-rich plasma (LP-PRP) and hyaluronic acid (HA) to a single dose of autologous microfragmented adipose tissue (AMAT) in patients with mild osteoarthritis at a two-year follow-up. Methods: Eighty symptomatic knees in fifty patients (mean age: 62.38 ± 11.88 years) with Kellgren-Lawrence grade 0 to 2 osteoarthritis were non blinded, randomly allocated into two equal groups. Group 1 consisted of 40 knees that received autologous LP-PRP + HA; Group 2 consisted of 40 knees treated with a single dose of AMAT injection. The outcomes were measured by Tegner, Marx, Visual Analogue Scale (VAS) for pain, International Knee Documentation Committee, and Knee Injury and Osteoarthritis Outcome Score (KOOS) at 6 (T1), 12 (T2), and 24 (T3) months. Adverse events were recorded at each follow-up timepoint. To assess score differences among subjects of the same gender and age, a subgroup analysis was performed. Results: Both groups had significant clinical and functional improvement at 6, 12, and 24 months (p < 0.05). Comparing the two groups, the AMAT groups showed significantly higher pre-operative Marx score (3.35 ± 4.91 vs. 1.78 ± 3.91) and VAS score (5.03 ± 2.02 vs. 3.85 ± 1.68) (p < 0.05), higher VAS (3.89 ± 2.51 vs. 2.64 ± 2.00) at T2 and KOOS-ADL (79.60 ± 20.20 vs. 65.68 ± 23.62), and lower KOOS-Sports (50.30 ± 30.15 vs. 68.35 ± 30.39) at T3 (p < 0.05). No patient from either group had experienced major adverse effects. In the LP-PRP group 12 (30%) patients presented swelling, redness, and mild pain for one day after injection and two patients had synovitis for two days and required paracetamol and local ice. In AMAT group 5 (12.5%) patients had ecchymosis and bruising at the fat aspiration site for three days. Conclusion: AMAT did not show significant superior clinical improvement compared with three LP-PRP combined with HA injections in terms of functional improvement at different follow-up points. Both procedures were safe with no major complications reporting good results at mid-term follow-up, improving knee function, pain, and quality of live regardless of age and gender. Level of evidence: Level I—Prospective Randomized Clinical Trial. [ABSTRACT FROM AUTHOR]

Human-adipose-tissue-derived mesenchymal stromal cells (AD-MSCs) are currently being tested as autologous-cell-based therapies for use in tissue healing and regeneration. Recent studies have also demonstrated that AD-MSC-derived exosomes contribute to tissue repair and peripheral nerve regeneration. Subcutaneous abdominal adipose tissue (AAT) is divided into two layers: the superficial layer (sAAT) and the deep layer (dAAT). However, it is unclear whether there are particular characteristics of each layer in terms of AD-MSC regenerative potential. Using AD-MSCs purified and characterized from three abdominoplasties, we compared their secretomes and exosome functions to identify which layer may be most suitable as a source for cell therapy. Phenotypical analysis of the AD-MSCs containing stromal vascular fraction did not reveal any difference between the two layers. The AD-MSC secretomes showed a very similar pattern of cytokine content and both layers were able to release exosomes with identical characteristics. However, compared to the secretome, the released exosomes showed better biological properties. Interestingly, dAAT exosomes appeared to be more effective on neuromodulation, whereas neither sAAT nor dAAT-derived exosomes had significant effects on endothelial function. It thus appears that AD-MSC-derived exosomes from the two abdominal adipose tissue layers possess different features for cell therapy. [ABSTRACT FROM AUTHOR]

This systematic review aims to describe the clinical outcomes, safety, and efficacy of autologous fat grafting (AFG) in breast reconstruction. We have reviewed 15 studies that encompass various aspects of AFG, including patient-reported outcomes, fat grafting techniques, immediate reconstruction, aesthetic evaluation, pain alleviation, stromal vascular fraction enhancement, oncological safety, and clinical outcomes with different processing techniques. Overall, the studies suggest that AFG is a safe and effective method for breast reconstruction, with promising results in improving breast aesthetics and reducing postoperative pain. Although lipofilling with autologous fat is widely used in breast reconstruction, further research is needed to optimize fat grafting techniques and determine long-term oncological safety. [ABSTRACT FROM AUTHOR]

The osteogenic and chondrogenic differentiation ability of adipose-derived mesenchymal stromal cells (ASCs) and their potential therapeutic applications in bone and cartilage defects are reported in this review. This becomes particularly important when these disorders can only be poorly treated by conventional therapeutic approaches, and tissue engineering may represent a valuable alternative. Being of mesodermal origin, ASCs can be easily induced to differentiate into chondrocyte-like and osteocyte-like elements and used to repair damaged tissues. Moreover, they can be easily harvested and used for autologous implantation. A plethora of ASC-based strategies are being developed worldwide: they include the transplantation of freshly harvested cells, in vitro expanded cells or predifferentiated cells. Moreover, improving their positive effects, ASCs can be implanted in combination with several types of scaffolds that ensure the correct cell positioning; support cell viability, proliferation and migration; and may contribute to their osteogenic or chondrogenic differentiation. Examples of these strategies are described here, showing the enormous therapeutic potential of ASCs in this field. For safety and regulatory issues, most investigations are still at the experimental stage and carried out in vitro and in animal models. Clinical applications have, however, been reported with promising results and no serious adverse effects. [ABSTRACT FROM AUTHOR]

Background: The use of bone morphogenic protein and mesenchymal stem cells has shown promise in promoting bone regeneration in calvarial defects. However, a systematic review of the available literature is needed to evaluate the efficacy of this approach. Methods: We comprehensively searched electronic databases using MeSH terms related to skull defects, bone marrow mesenchymal stem cells, and bone morphogenic proteins. Eligible studies included animal studies that used BMP therapy and mesenchymal stem cells to promote bone regeneration in calvarial defects. Reviews, conference articles, book chapters, and non-English language studies were excluded. Two independent investigators conducted the search and data extraction. Results: Twenty-three studies published between 2010 and 2022 met our inclusion criteria after a full-text review of the forty-five records found in the search. Eight of the 23 studies used mice as models, while 15 used rats. The most common mesenchymal stem cell was bone marrow-derived, followed by adipose-derived. BMP-2 was the most popular. Stem cells were embedded in Scaffold (13), Transduction (7), and Transfection (3), and they were delivered BMP to cells. Each treatment used 2 × 104–1 × 107 mesenchymal stem cells, averaging 2.26 × 106. Most BMP-transduced MSC studies used lentivirus. Conclusions: This systematic review examined BMP and MSC synergy in biomaterial scaffolds or alone. BMP therapy and mesenchymal stem cells in calvarial defects, alone, or with a scaffold regenerated bone. This method treats skull defects in clinical trials. The best scaffold material, therapeutic dosage, administration method, and long-term side effects need further study. [ABSTRACT FROM AUTHOR]

Transplantation of brown adipose tissue (BAT), engineered thermogenic progenitor cells, and adipocytes have received much attention for the improvement of obesity and metabolic disorders. However, even though the thermogenic and metabolic potential exists early after transplantation, the whitening of the brown fat graft occurs with metabolic function significantly impaired. In this review, specific experiment designs, graft outcomes, and metabolic benefits for the transplantation of BAT or engineered cells will be discussed. The current advancements will offer guidance to further investigation, and the obstacles appearing in previous studies will require innovation of BAT transplantation methods. [ABSTRACT FROM AUTHOR]

The objective was to test the hypothesis of no difference in radiographic outcome after maxillary sinus floor augmentation (MSFA) with allogeneic adipose tissue-derived stem cells (ASCs) seeded on deproteinized bovine bone mineral (DBBM) (test) compared with excipient on DBBM (control). Eighteen minipigs were assigned into three groups of six animals and euthanised after one month (T1), two months (T2), and four months (T3), respectively. Each maxillary sinus was randomly allocated to either test or control with an equal volume of graft. Computed tomography scans (CTs) after MSFA (T0) were compared with CTs after euthanasia to evaluate graft volume (GV) changes and bone density (BD) using three-dimensional measurements and Hounsfield units. GV was larger in test compared with control at T1 (P = 0.046), whereas GV was larger in control compared with test at T3 (P = 0.01). BD increased from T0 to T1-T3 (P < 0.001) with both treatments. Higher BD was observed in control compared with test at T3 (P = 0.01), while no significant difference was observed at T1 and T2. Conclusively, the present study demonstrate that allogeneic ASCs seeded on DBBM in conjunction with MSFA seemed not to improve the radiographic outcome compared with excipient on DBBM. However, radiological outcomes need to be supplemented by bone histomorphometry before definitive conclusions can be provided about the beneficial use of allogeneic ASCs seeded on DBBM in conjunction with MSFA compared with DBBM alone. [ABSTRACT FROM AUTHOR]

Background: Autologous fat transplantation (AFT) for soft-tissue enhancement is a frequent procedure that lacks a widely approved method. Objective: The aim of this study is to evaluate AFT outcomes in facial reconstructive surgeries by using meta-analysis. Materials and Methods: An electronic databases search was done on PubMed, EMBASE, and Cochrane. We screened the results, then extracted the data. Meta-analysis was done using the Open Meta-analyst program. Results: We included 62 studies in our meta-analysis, which have various study designs, including cohort, case series, and trials. They included 2326 unique patients. Our meta-analysis revealed a high rate of the patient (91.7%) and surgeon (93.1%) satisfaction with AFT surgeries which is confirmed by high scores of 7.8 and 7.9, respectively. Complications resemble a minor ratio of 2.1 %. Conclusion: In experienced hands, autologous fat transfer is an effective way to correct facial deformities and leads to greater patient and surgeon satisfaction, as well as a lower risk of complications. [ABSTRACT FROM AUTHOR]

Background: Obesity is associated with an increased risk of developing clear cell renal cell carcinoma (ccRCC), but paradoxically there is a positive association between obesity and surveillance. Purpose: To investigate the relationship between nucleus grade classification and body composition in patients with matched co-morbid conditions with non-metastatic ccRCC. Materials and Methods: A total of 253 patients with non-metastatic ccRCC were included in the study. Body composition was assessed with abdominal computed tomography (CT) using an automated artificial intelligence software. Both adipose and muscle tissue parameters of the patients were calculated. In order to investigate the net effect of body composition, propensity score matching (PSM) procedure was applied over age, sex, and T stage parameters. In this way, selection bias and imbalance between groups were minimized. Univariate and multivariate logistic regression analyses were performed to identify the association between body composition and WHO/ISUP grade (I–IV). Result: When the body composition of the patients was examined without matching the conditions, it was found that the subcutaneous adipose tissue (SAT) values were higher in patients with low grades (P = 0.001). Normal attenuation muscle area (NAMA) was higher in high-grade patients than low-grade patients (P < 0.05). In the post-matching evaluation, only SAT/NAMA was found to be associated with high-grade ccRCC (univariate analysis: odds ratio [OR]=0.899, 95% confidence interval [CI]=0.817−0.988, P = 0.028; multivariate analysis: OR=0.922, 95% CI=0.901−0.974, P = 0.042). Conclusion: CT-based body composition parameters can be used as a prognostic marker in predicting nuclear grade when age, sex, and T stage match conditions. This finding offers a new perspective on the obesity paradox. [ABSTRACT FROM AUTHOR]

Objective: Diet structure has changed greatly over the last few decades, and high-calorie diets have become an integral part of people's daily diet, as well as the important cause of obesity in society. Several organ systems, including the skeletal system, are seriously affected by high-fat-diets (HFD) in the world. There is, however, still a lack of knowledge about the effects of HFD on bone regeneration and the possible mechanisms involved. In this study, the difference in bone regeneration between rats under HFD and low-fat-diets (LFD) was evaluated by monitoring the process of bone regeneration in distraction osteogenesis (DO) model animals, as well as the possible mechanisms. Methods: A total of 40 Sprague Dawley (SD) rats (5 weeks old) were randomly divided into HFD group (n=20) and LFD group (n=20). Except for feeding methods, there were no differences between the two groups in terms of treatment conditions. All animals received the DO surgery eight weeks after starting to feed. After a delay of 5 days (latency phase), the active lengthening phase was performed for 10 days (0.25 mm/12 h), and the consolidation phase followed for 42 days. An observational study of bone included radioscopy (once a week), micro-computed tomography (CT), general morphology, biomechanics, histomorphometry, and immunohistochemistry. Result: The results showed that HFD group had a higher body weight than LFD group after 8, 14, and 16 weeks of feeding. Furthermore, at the final observation, there were statistically significant differences between LFD group and HFD group in terms of total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) levels. Additionally, observations on bone regeneration showed a slower regeneration and a lower biomechanical strength in HFD group than LFD group, based on radiography, micro-CT, general morphology, biomechanics, histomorphometry, and immunohistochemistry. Conclusion: In this study, HFD resulted in elevated blood lipids, increased adipose differentiation at the bone marrow level, and delayed bone regeneration. The pieces of evidence are beneficial to better understand the association between diet and bone regeneration and to adjust the diet optimally for fracture patients. [ABSTRACT FROM AUTHOR]

Background: Cancer cachexia is a deadly wasting syndrome that accompanies various diseases (including ~ 50% of cancers). Clinical studies have established that cachexia is not a nutritional deficiency and is linked to expression of certain proteins (e.g., interleukin-6 and C-reactive protein), but much remains unknown about this often fatal syndrome. Methods: First, cachexia was created in experimental mouse models of lung cancer. Samples of human lung cancer were used to identify the association between the serum lipocalin 2 (LCN2) level and cachexia progression. Then, mouse models with LCN2 blockade or LCN2 overexpression were used to ascertain the role of LCN2 upon ferroptosis and cachexia. Furthermore, antibody depletion of tissue-infiltrating neutrophils (TI-Neu), as well as myeloid-specific-knockout of Lcn2, were undertaken to reveal if LCN2 secreted by TI-Neu caused cachexia. Finally, chemical inhibition of ferroptosis was conducted to illustrate the effect of ferroptosis upon tissue wasting. Results: Protein expression of LCN2 was higher in the wasting adipose tissue and muscle tissues of experimental mouse models of lung cancer cachexia. Moreover, evaluation of lung cancer patients revealed an association between the serum LCN2 level and cachexia progression. Inhibition of LCN2 expression reduced cachexia symptoms significantly and inhibited tissue wasting in vivo. Strikingly, we discovered a significant increase in the number of TI-Neu in wasting tissues, and that these innate immune cells secreted high levels of LCN2. Antibody depletion of TI-Neu, as well as myeloid-specific-knockout of Lcn2, prevented ferroptosis and tissue wasting in experimental models of lung cancer cachexia. Chemical inhibition of ferroptosis alleviated tissue wasting significantly and also prolonged the survival of cachectic mice. Conclusions: Our study provides new insights into how LCN2-induced ferroptosis functionally impacts tissue wasting. We identified LCN2 as a potential target in the treatment of cancer cachexia. [ABSTRACT FROM AUTHOR]

In recent decades, adipose tissue transplantation has become an essential treatment modality for tissue (volume) restoration and regeneration. The regenerative application of adipose tissue has only recently proven its usefulness; for example, the method is useful in reducing dermal scarring and accelerating skin-wound healing. The therapeutic effect is ascribed to the tissue stromal vascular fraction (tSVF) in adipose tissue. This consists of stromal cells, the trophic factors they secrete and the extracellular matrix (ECM), which have immune-modulating, pro-angiogenic and anti-fibrotic properties. This concise review focused on dermal regeneration using the following adipose-tissue components: adipose-tissue-derived stromal cells (ASCs), their secreted trophic factors (ASCs secretome), and the ECM. The opportunities of using a therapeutically functional scaffold, composed of a decellularized ECM hydrogel loaded with trophic factors of ASCs, to enhance wound healing are explored as well. An ECM-based hydrogel loaded with trophic factors combines all regenerative components of adipose tissue, while averting the possible disadvantages of the therapeutic use of adipose tissue, e.g., the necessity of liposuction procedures with a (small) risk of complications, the impossibility of interpatient use, and the limited storage options. [ABSTRACT FROM AUTHOR]

Background: Intra-articular injection of adipose-derived stem cells, which are divided into adipose-derived mesenchymal stem cells (ASCs) and adipose-derived stromal vascular fractions (ADSVFs), has been reported to be a viable treatment modality for knee osteoarthritis (OA); however, its efficacy remains limited. Purpose: This study aimed to provide comprehensive information about the efficacy and safety of intra-articular injections of autologous ASCs and ADSVFs without adjuvant treatment in patients with knee OA. Study Design: Meta-analysis; Level of evidence, 1. Methods: A systematic search of the MEDLINE, Embase, Web of Science, and Cochrane Library databases was performed to identify randomized controlled trials (RCTs) that evaluated the efficacy and safety of intra-articular injections of autologous ASCs or ADSVFs without adjuvant treatments compared with placebo or hyaluronic acid in patients with knee OA. Clinically, the 100-mm visual analog scale for pain relief and the Western Ontario and McMaster Universities Osteoarthritis Index for functional improvement were implemented. Radiologically, cartilage status was assessed using magnetic resonance imaging (MRI). Procedure-related knee pain, swelling, and adverse events (AEs) were evaluated for safety. Additionally, we performed subgroup analyses comparing ASCs versus ADSVFs. Methodological quality was assessed using the modified Coleman Methodology Score (mCMS). Results: A total of 5 RCTs were included in this study. Based on the meta-analysis, ASCs or ADSVFs showed significantly better pain relief at 6 months (Z = 7.62; P <.0001) and 12 months (Z = 7.21; P <.0001) and functional improvement at 6 months (Z = 4.13; P <.0001) and 12 months (Z = 3.79; P =.0002), without a difference in procedure-related knee pain or swelling compared with controls. Although a meta-analysis with regard to cartilage improvements was not performed owing to heterogeneous MRI assessment, 3 studies reported significantly improved cartilage status after the injection. No serious AEs associated with ASCs or ADSVFs were reported. Subgroup analyses showed similar efficacy between ASC and ADSVF treatments. The median mCMS was 70 (range, 55-75). Conclusion: For patients with knee OA, intra-articular injection of autologous ASCs or ADSVFs without adjuvant treatment showed remarkable clinical efficacy and safety at short-term follow-up. Some degree of efficacy has been shown for cartilage regeneration in knee OA, although the evidence remains limited. Further RCTs that directly compare ASCs and ADSVFs are needed. [ABSTRACT FROM AUTHOR]

Simple Summary: In recent years, there have been relevant advances in the use of surgery, radiation therapy, and chemotherapy for the treatment of malignant tumors of the head and neck. Extensive tumor resection and radical radiotherapy frequently result in altered form and function of orofacial structures that can severely impact the patient's quality of life. This study reports the benefits obtained with the injection of autologous fat to correct the deformities and improve functionality in a series of 40 patients who have been treated for head and neck cancer. Esthetic improvement was obtained in 77.5% of patients and functional improvement in 89.2%. In addition, there was a high degree of satisfaction regarding esthetic improvement and 92.5% of patients would recommend the procedure to other patients in the same situation. The injection of autologous fat is an effective procedure for the management of sequelae of head and neck cancer treatment. A single-center retrospective study was designed to assess the outcomes of autologous fat grafting for improving surgery- and radiotherapy-related sequelae in 40 patients with head and neck cancer. All patients underwent surgical resection of primary tumors and radiotherapy (50–70 Gy) and were followed over 12 months after fat grafting. Eligibility for fat grafting procedures included complete remission after at least 3 years of oncological treatment. The cervical and paramandibular regions were the most frequently treated areas. Injected fat volumes ranged between 7.5 and 120 mL (mean: 23 mL). Esthetic improvement was obtained in 77.5% of patients, being significant in 17.5%, and functional improvement in 89.2%, being significant in 29.7% of patients. Minor complications occurred in three patients. There was a high degree of satisfaction regarding esthetic improvement, global satisfaction, and 92.5% of patients would recommend the procedure. This study confirms the benefits of fat grafting as a volumetric correction reconstructive strategy with successful cosmetic and functional outcomes in patients suffering from sequelae after head and neck cancer treatment. [ABSTRACT FROM AUTHOR]

Background: We aimed to determine the effects of systemic therapy with autologous adipose tissue derived mesenchymal stem cells (AD-MSCs) on different parameters of peritoneal function and inflammation in peritoneal dialysis (PD) patients. Methods: We enrolled nine PD patients with ultrafiltration failure (UFF). Patients received 1.2 ± 0.1 x 106 cell/kg of AD-MSCs via cubital vein and were then followed for six months at time points of baseline, 3, 6, 12, 16 and 24 weeks after infusion. UNIPET was performed for assessment of peritoneal characteristics at baseline and weeks 12 and 24. Systemic and peritoneal levels of tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), IL-2 and CA125 (by ELISA) and gene expression levels of transforming growth factor beta (TGF-β), smooth muscle actin (α-SMA) and fibroblast-specific protein-1 (FSP-1) in PD effluent derived cells (by quantitative real-time PCR) were measured at baseline and weeks 3, 6, 12, 16 and 24. Results: Slight improvement was observed in the following UF capacity indices: free water transport (FWT, 32%), ultrafiltration - small pore (UFSP, 18%), ultrafiltration total (UFT, 25%), osmotic conductance to glucose (OCG, 25%), D/P creatinine (0.75 to 0.70), and Dt/D0 glucose (0.23 to 0.26). There was a slight increase in systemic and peritoneal levels of CA125 and a slight decrease in gene expression levels of TGF-β, α-SMA and FSP-1 that was more prominent at week 12 and vanished by the end of the study. Conclusion: Our results for the first time showed the potential of MSCs for treatment of peritoneal damage in a clinical trial. Our results could be regarded as hypothesis suggestion and will need confirmation in future studies. [ABSTRACT FROM AUTHOR]

Overweight and obesity have become a world-wide problem. However, effective intervention approaches are limited. Brown adipose tissue, which helps maintain body temperature and contributes to thermogenesis, is dependent on uncoupling protein1. Over the last decade, an in-creasing number of studies have found that activating brown adipose tissue and browning of white adipose tissue can protect against obesity and obesityrelated metabolic disease. Brown adipose tissue has gradually become an appealing therapeutic target for the prevention and re-versal of obesity. However, some important issues remain unresolved. It is not certain whether increasing brown adipose tissue activity is the cause or effect of body weight loss or what the risks might be for sympathetic nervous system-dependent non-shivering thermogenesis. In this review, we comprehensively summarize approaches to activating brown adipose tissue and/or browning white adipose tissue, such as cold exposure, exercise, and small-molecule treatment. We highlight the functional mechanisms of small-molecule treatment and brown adipose tissue transplantation using batokine, sympathetic nervous system and/or gut microbiome. Finally, we discuss the causality between body weight loss induced by bariatric surgery, exercise, and brown adipose tissue activity. [ABSTRACT FROM AUTHOR]

Endometriosis is a common gynecological disease that affects women of reproductive age in which the uterine endometrium grows outside the uterus. Origin of the ectopic endometrium is thought to be the retrograde endometrium through the oviducts. However, factors that determine the adherence and proliferation of the ectopic endometrium have not been revealed. Importantly, systemic autoimmune diseases are considered a key factor in the endometriosis onset. Herein, we established a surgical endometriosis rodent model using autoimmune disease-prone MRL/MpJ-Faslpr/lpr (MRL/lpr) and MRL/+ mice to provide basic evidence of the relationship between autoimmune disease and endometriosis. Endometriosis lesions were successfully induced in two regions after transplanting uterine tissues from donor mice into the peritoneal cavity of recipient mice: the peritoneum or adipose tissue around the transplantation point (proximal lesions) and the gastrosplenic ligament or intestinal mesentery far from the transplantation site (distal lesions). Distal lesions were observed only in MRL/lpr mice, whereas endometriosis lesions showed no genotypeor region-related differences in the histology and distribution of sex hormone receptors and T cells. In contrast, transplanted uterine tissues in donor MRL/lpr mice exhibited a large infiltration of T cells in the lamina propria. Splenomegaly was more common in recipient than that in donor MRL/lpr mice. These results suggest that the infiltration of endogenous T cells in the endometrium alters the growth features of ectopic endometrium, possibly affecting the severity of endometriosis in patients with systemic autoimmune diseases. [ABSTRACT FROM AUTHOR]

Objective: The goal of this study was to review the metabolic effects of fat transplantation. Methods: Fat (adipose tissue [AT]) transplantation has been performed extensively for many years in the cosmetic reconstruction industry. However, not all fats are equal. White, brown, and beige AT differ in energy storage and use. Brown and beige AT consume glucose and lipids for thermogenesis and, theoretically, may provide greater metabolic benefit in transplantation. Here, the authors review the metabolic effects of AT transplantation. Results: Removal of subcutaneous human AT does not have beneficial metabolic effects. Most studies find no benefit from visceral AT transplantation and some studies report harmful effects. In contrast, transplantation of inguinal or subcutaneous AT in mice has positive effects. Brown AT transplant studies have variable results depending on the model but most show benefit. Conclusions: Many technical improvements have optimized fat grafting and transplantation in cosmetic surgery. Transplantation of subcutaneous AT has the potential for significant metabolic benefits, although there are few studies in humans or using human AT. Brown AT transplantation is beneficial but not readily feasible in humans thus ex vivo "beiging" may be a useful strategy. AT transplantation may provide clinical benefits in metabolic disorders, especially in the setting of lipodystrophy. [ABSTRACT FROM AUTHOR]

Background: Clinical trials are currently underway to investigate the efficacy of intra-articular administration of mesenchymal stromal cells (MSCs) to mitigate osteoarthritis (OA) progression in the knee. Although multiple MSC sources exist, studies have yet to determine whether differences in therapeutic efficacy exist between them. Purpose: To compare the ability of intra-articularly injected adipose-derived MSCs (AD-MSCs) and amnion-derived MSCs (AM-MSCs) to mitigate the progression of knee OA in a small animal model of spontaneous OA, as well as to compare the therapeutic potential of MSCs in hyaluronic acid (HA) and in HA only with saline (OA) controls. Study Design: Controlled laboratory study. Methods: Injections of AD-MSCs or AM-MSCs suspended in HA or HA only were performed in the rear stifle joints of 3-month-old Dunkin Hartley guinea pigs (DHGPs). Repeat injections occurred at 2 and 4 months after the initial injection in each animal. Contralateral limbs received saline injections and served as untreated controls. Subsequently, joints were analyzed for osteoarthritic changes of the cartilage and subchondral bone via histologic and biochemical analyses. To evaluate MSC retention time in the joint space, DHGPs received a single intra-articular injection of fluorescently labeled AD-MSCs or AM-MSCs, and the fluorescence intensity was longitudinally tracked via an in vivo imaging system. Results: No statistically significant differences in outcomes were found when comparing the ability of AD-MSCs and AM-MSCs to mitigate OA. However, the injection of AD-MSCs, AM-MSCs, and HA-only treatments more effectively mitigated cartilage damage compared with that of saline controls by demonstrating higher amounts of cartilage glycosaminoglycan content and improved histological proteoglycan scoring while reducing the percentage of osteophytes present. Conclusion: Intra-articular injection of AD-MSCs, AM-MSCs, or HA only was able to similarly mitigate the progression of cartilage damage and reduce the percentage of osteophytes compared with that of saline controls in the DHGP. However, this study was unable to establish the superiority of AD-MSCs versus AM-MSCs as a treatment to mitigate spontaneous OA. Clinical Relevance: MSCs demonstrate the ability to mitigate the progression of knee OA and thus may be used in a prophylactic approach to delay the need for end-stage treatment strategies. [ABSTRACT FROM AUTHOR]

Finally, a Burow's full-thickness skin graft with an underlying Burow's adipose graft from the upper arm to cover the exposed bone was considered. Reconstructive options for large defects of the upper extremity include primary closure, secondary intention healing, purse string closure, local tissue flaps, free flaps, and grafts. Split thickness grafts over exposed bone may result in tissue necrosis and likely concavity in final scar appearance. [Extracted from the article]

Determining to what extent adipose tissue dysfunction may cause skeletal muscle insulin resistance, and to what extent adipose tissue dysfunction and skeletal muscle insulin resistance correlate merely because they are caused by similar systemic processes, requires further work. To assess putative mechanisms that could affect adipose tissue insulin action and link dysfunctional adipose tissue with skeletal muscle insulin resistance, the authors assessed subcutaneous abdominal adipose tissue morphology and also performed adipose tissue proteomic and skeletal muscle lipidomic analyses. First, although the glucose disposal rate during the HECP was adjusted for the plasma insulin concentration to evaluate skeletal muscle insulin sensitivity, adipose tissue insulin sensitivity was evaluated without taking into account potential differences in plasma insulin between groups or individuals. [Extracted from the article]

Aiming to reveal the role of ADCS-Exos in secretion of inflammatory factors, Th17 and regulatory T (Treg) cell differentiation from naïve CD4+ T cells in hypertrophic scaring formation and maturation is explored. ELISA, qRT-PCR, and immunoblotting are performed to assay the local inflammatory factors IL-6, IL-10, IL-17A, and TNF-α, and transcriptional factors of RORϒt and Foxp3, in scaring tissue from patients and mice wound models treated with or without ADCS-Exos. Immunohistochemistry staining and immunoblotting are conducted to assay the extracellular matrix (ECM) deposition in vitro and in vivo. The results show that IL-6, IL-10, IL-17A, TNF-α, RORϒt, and Foxp3 are increased on mRNA and protein levels in hypertrophic scaring compared with atrophic scaring and normal skin. Naïve CD4+ T cells treated with ADCS-Exos in vitro can produce significantly less IL-6, IL-17A, TNF-α, and RORϒt and more IL-10 and Foxp3 on mRNA and protein levels. In addition, mice in ADSC-Exos-treated group demonstrate less collagen deposition; decreased IL-17A, TNF-α, and RORϒt; and increased IL-10 and Foxp3 production. [ABSTRACT FROM AUTHOR]

Background: Localized scleroderma causes cosmetic disfigurement, joint contractures, and other functional impairment, but no currently available medications can reverse the resulting skin lesions. Fat grafting is beneficial for reversing skin fibrosis; however, the mechanism by which adipose tissue transplantation contributes to lesion improvement has not been fully clarified. The purpose of our study was to verify the therapeutic effect of fat grafts in reversing skin fibrosis. Methods: Inguinal fat pads from AdipoqCreER+;mT/mG mice, which were treated with tamoxifen, were transplanted to the skin lesion in bleomycin-treated wild-type C57 mice. Tdtomato transgenic mice-derived adipocytes, adipose-derived stem cells (ASCs), dedifferentiated adipocytes (DAs) were embedded in matrigel and transplanted beneath the skin lesion of bleomycin-treated wild-type C57 mice. A transwell co‐culture system was used to verify the effect of ASCs, adipocytes or DAs on scleroderma fibroblasts or monocytes. Results: Adipocytes from the fat grafts could undergo dedifferentiation and redifferentiation for dermal adipose tissue re-accumulation within the skin lesion. Moreover, compared with ASCs and adipocytes, DAs show greater potency of inducing adipogenesis. ASCs and DAs showed comparable effect on inducing angiogenesis and suppressing macrophage infiltration in fibrotic skin. Co-culture assay showed that DAs and ASCs were able to reduce fibrosis-related genes in human scleroderma fibroblasts and drive M2 macrophage polarization. Conclusion: Our results indicated that adipocytes would transform into a more functional and dedifferentiated state and reverse dermal fibrosis, by promoting dermal adipose tissue regeneration, improving angiogenesis, suppressing macrophage-mediated inflammation and myofibroblast accumulation. [ABSTRACT FROM AUTHOR]