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Peripheral nerve injuries are common complications in surgical and dental practices, often resulting in functional deficiencies and reduced quality of life. Current treatment choices, such as autografts, have limitations, including donor site morbidity and suboptimal outcomes. Adipose-derived stem cells (ADSCs) have shown assuring regenerative potential due to their accessibility, ease of harvesting and propagation, and multipotent properties. This review investigates the therapeutic potential of ADSCs in peripheral nerve regeneration, focusing on their use in bioengineered nerve conduits and supportive microenvironments. The analysis is constructed on published case reports, organized reviews, and clinical trials from Phase I to Phase III that investigate ADSCs in managing nerve injuries, emphasizing both peripheral and orofacial applications. The findings highlight the advantages of ADSCs in promoting nerve regeneration, including their secretion of angiogenic and neurotrophic factors, support for cellular persistence, and supplementing scaffold-based tissue repair. The regenerative capabilities of ADSCs in peripheral nerve injuries offer a novel approach to augmenting nerve repair and functional recovery. The accessibility of adipose tissue and the minimally invasive nature of ADSC harvesting further encourage its prospective application as an autologous cell source in regenerative medicine. Future research is needed to ascertain standardized protocols and optimize clinical outcomes, paving the way for ADSCs to become a mainstay in nerve regeneration. [ABSTRACT FROM AUTHOR]

Background/Objectives: Research on the roles of stem cells in necrotizing enterocolitis (NEC) has primarily focused on the effects of bone marrow- and amniotic fluid-derived stem cells in mitigating the clinical manifestations of the disease. However, the potential of adipose tissue-derived stem cells (ADSCs) remains unexplored in this context. The aim of this study was to evaluate the therapeutic potential of ADSC administration during the active inflammatory phase of NEC, with a specific focus on reducing the levels of the inflammatory cytokines IL-1 and IL-6. Methods: A self-modified hypoxia–hypothermia–formula feeding rat NEC model was employed. A total of 117 rat pups were divided into two groups: a treatment group (NEC-ADSC, n = 55) and a control group (NEC-PLCB (placebo), n = 62). In the NEC-ADSC group, ADSCs were administered intraperitoneally 24 h into the NEC protocol. After 72 h, bowel and fluid samples were collected for analysis. Results: The analysis revealed no significant effect on NEC histopathology (p = 0.347) or on the levels of IL-1 and IL-6 (p = 0.119 and p = 0.414, respectively). Conclusions: The administration of adipose tissue-derived stem cells after the onset of necrotizing enterocolitis does not reduce the levels of inflammatory cytokines IL-1 and IL-6, nor does it influence the histopathological outcomes of the disease in the rat model. Further research is needed to explore the potential therapeutic role of adipose tissue-derived stem cells in the treatment of necrotizing enterocolitis. [ABSTRACT FROM AUTHOR]

There is little research concerning the role of stem cells in necrotizing enterocolitis (NEC). Bone marrow-derived mesenchymal stem cells (BMDSC) and amniotic fluid-derived stem cells significantly reduced the amount and severity of NEC in the animal models. ADSCs share similar surface markers and differentiation potential with BMDSCs. Their potential role in the setting of NEC has not been researched before. The hypothesis of the study was that prophylactic intraperitoneal administration of ADSCs before the onset of the disease will result in limiting the inflammatory response, effecting a lower incidence of NEC. On a molecular level, this should result in lowering the levels of inflammatory cytokines IL-1 and IL-6. The local ethical committee for animal experiments approval was acquired (WAW2/093/2021). We utilized a self-modified rat NEC model based on single exposure to hypothermia, hypoxia, and formula feeding. One hundred and twenty-eight rat puppies were divided into two groups—prophylaxis (ADSC-NEC, n = 66) and control group (NEC-PLCB, n = 62)—to measure the influence of ADSCs administration on the inflammatory changes in NEC, the level of cell engraftment, and the histopathology of the disease. The analysis did not show a significant effect on histopathology between groups, H(2) = 2.12; p = 0.347; η²H = 0.00. The intensity of the NEC variable results was similar across the analyzed groups (NEC-PLCB and ADSC-NEC). For IL-1 and IL-6, the difference between the NEC-PLCB group and the ADSC-NEC group was statistically significant, p = 0.002 and p < 0.001, respectively. To conclude, administration of adipose tissue-derived stem cells before the onset of the disease lowers the levels of inflammatory cytokines IL-1 and IL-6 but does not affect the histopathological results in the rat model of NEC. [ABSTRACT FROM AUTHOR]

This study investigates the impact of acetylsalicylic acid (ASA), also known as aspirin, on adipose tissue-derived stem cells (ASCs), aiming to elucidate its dose-dependent effects on morphology, viability, proliferation, and osteogenic differentiation. Isolated and characterized human ASCs were exposed to 0 µM, 100 µM, 200 µM, 400 µM, 800 µM, 1000 µM, 10,000 µM, and 16,000 µM of ASA in vitro. Cell morphology, viability, and proliferation were evaluated with fluorescent live/dead staining, alamarBlue viability reagent, and CyQUANT® cell proliferation assay, respectively. Osteogenic differentiation under stimulation with 400 µM or 1000 µM of ASA was assessed with alizarin red staining and qPCR of selected osteogenic differentiation markers (RUNX2, SPP1, ALPL, BGLAP) over a 3- and 21-day-period. ASA doses ≤ 1000 µM showed no significant impact on cell viability and proliferation. Live/dead staining revealed a visible reduction in viable cell confluency for ASA concentrations ≥ 1000 µM. Doses of 10,000 µM and 16,000 µM of ASA exhibited a strong cytotoxic and anti-proliferative effect in ASCs. Alizarin red staining revealed enhanced calcium accretion under the influence of ASA, which was macro- and microscopically visible and significant for 1000 µM of ASA (p = 0.0092) in quantification if compared to osteogenic differentiation without ASA addition over a 21-day-period. This enhancement correlated with a more pronounced upregulation of osteogenic markers under ASA exposure (ns). Our results indicate a stimulatory effect of 1000 µM of ASA on the osteogenic differentiation of ASCs. Further research is needed to elucidate the precise molecular mechanisms underlying this effect; however, this discovery suggests promising opportunities for enhancing bone tissue engineering with ASCs as cell source. [ABSTRACT FROM AUTHOR]

Scaffolds made of degradable polymers, such as collagen, polyesters or polysaccharides, are promising matrices for fabrication of bioartificial vascular grafts or patches. In this study, collagen isolated from porcine skin was processed into a gel, reinforced with collagen particles and with incorporated adipose tissue-derived stem cells (ASCs). The cell-material constructs were then incubated in a DMEM medium with 2% of FS (DMEM_part), with added polyvinylalcohol nanofibers (PVA_part sample), and for ASCs differentiation towards smooth muscle cells (SMCs), the medium was supplemented either with human platelet lysate released from PVA nanofibers (PVA_PL_part) or with TGF-β1 + BMP-4 (TGF + BMP_part). The constructs were further endothelialised with human umbilical vein endothelial cells (ECs). The immunofluorescence staining of alpha-actin and calponin, and von Willebrand factor, was performed. The proteins involved in cell differentiation, the extracellular matrix (ECM) proteins, and ECM remodelling proteins were evaluated by mass spectrometry on day 12 of culture. Mechanical properties of the gels with ASCs were measured via an unconfined compression test on day 5. Gels evinced limited planar shrinkage, but it was higher in endothelialised TGF + BMP_part gel. Both PVA_PL_part samples and TGF + BMP_part samples supported ASC growth and differentiation towards SMCs, but only PVA_PL_part supported homogeneous endothelialisation. Young modulus of elasticity increased in all samples compared to day 0, and PVA_PL_part gel evinced a slightly higher ratio of elastic energy. The results suggest that PVA_PL_part collagen construct has the highest potential to remodel into a functional vascular wall. [ABSTRACT FROM AUTHOR]

The good availability and the large content of adult stem cells in adipose tissue has made it one of the most interesting tissues in regenerative medicine. Although lipofilling is one of the most frequent procedures in plastic surgery, the method still struggles with high absorption rates and volume losses of up to 70%. Therefore, many efforts have been made to optimize liposuction and to process the harvested tissue in order to increase fat graft retention. Because of their immunomodulatory properties, their cytokine secretory activity, and their differentiation potential, enrichment with adipose tissue-derived stem cells was identified as a promising tool to promote transplant survival. Here, we review the important parameters for lipofilling optimization. Finally, we present a new method for the enrichment of lipoaspirate with adipose tissue-derived stem cells and discuss the parameters that contribute to fat graft survival. [ABSTRACT FROM AUTHOR]

The physical stresses during cryopreservation affect stem cell survival and further proliferation. To minimize or prevent cryoinjury, cryoprotective agents (CPAs) are indispensable. Despite the widespread use of 10% dimethyl sulfoxide (DMSO), there are concerns about its potential adverse effects. To bypass those effects, combinations of CPAs have been investigated. This study aimed to verify whether high-molecular-hyaluronic acid (HMW-HA) serves as a cryoprotectant when preserving human mesenchymal stem cells (hMSCs) to reduce the DMSO concentration in the cryopreservation medium. We studied how 0.1% or 0.2% HMW-HA combined with reduced DMSO concentrations (from 10% to 5%, and 3%) affected total cell count, viability, immunophenotype, and differentiation potential post-cryopreservation. Immediately after cell revival, the highest total cell count was observed in 10% DMSO-stored hMSC. However, two weeks after cell cultivation an increased cell count was seen in the HMW-HA-stored groups along with a continued increase in hMSCs stored using 3% DMSO and 0.1% HMW-HA. The increased total cell count corresponded to elevated expression of stemness marker CD49f. The HA-supplemented cryomedium did not affect the differential potential of hMSC. Our results will participate in producing a ready-to-use product for cryopreservation of mesenchymal stem cells. [ABSTRACT FROM AUTHOR]

Previous anatomical studies have shown different functional zones in human nasal septal cartilage (NC). These zones differ in respect to histological architecture and biochemical composition. The aim of this study was to investigate the influence of these zones on the fate of stem cells from a regenerative perspective. Therefore, decellularized porcine septal cartilage was prepared and subjected to histological assessment to demonstrate its equivalence to human cartilage. Decellularized porcine NC (DPNC) exposed distinct surfaces depending on two different histological zones: the outer surface (OS), which is equivalent to the superficial zone, and the inner surface (IS), which is equivalent to the central zone. Human adipose tissue-derived stem cells (ASCs) were isolated from the abdominal fat tissue of five female patients and were seeded on the IS and OS of DPNC, respectively. Cell seeding efficiency (CSE), vitality, proliferation, migration, the production of sulfated glycosaminoglycans (sGAG) and chondrogenic differentiation capacity were evaluated by histological staining (DAPI, Phalloidin, Live-Dead), biochemical assays (alamarBlue®, PicoGreen®, DMMB) and the quantification of gene expression (qPCR). Results show that cell vitality and CSE were not influenced by DPNC zones. ASCs, however, showed a significantly higher proliferation and elevated expression of early chondrogenic differentiation, as well as fibrocartilage markers, on the OS. On the contrary, there was a significantly higher upregulation of hypertrophy marker MMP13 (p < 0.0001) and GAG production (p = 0.0105) on the IS, whereas cell invasion into the three-dimensional DPNC was higher in comparison to the OS. We conclude that the zonal-dependent distinct architecture and composition of NC modulates activities of ASCs seeded on DPNC. These findings might be used for engineering of cartilage substitutes needed in facial reconstructive surgery that yield an equivalent histological and functional structure, such as native NC. [ABSTRACT FROM AUTHOR]

Adipose tissue-derived stem cells (ADSCs) are pluripotent mesenchymal stem cells found in relatively high percentages in the adipose tissue and able to self-renew and differentiate into many different types of cells. "Extracellular vesicles (EVs), small membrane vesicular structures released during cell activation, senescence, or apoptosis, act as mediators for long distance communication between cells, transferring their specific bioactive molecules into host target cells". There is a general consensus on how to define and isolate ADSCs, however, multiple separation and characterization protocols are being used in the present which complicate the results' integration in a single theory on ADSCs' and their derived factors' way of action. Metabolic syndrome and type 2 diabetes mellitus (T2DM) are mainly caused by abnormal adipose tissue size, distribution and metabolism and so ADSCs and their secretory factors such as EVs are currently investigated as therapeutics in these diseases. Moreover, due to their relatively easy isolation and propagation in culture and their differentiation ability, ADSCs are being employed in preclinical studies of implantable devices or prosthetics. This review aims to provide a comprehensive summary of the current knowledge on EVs secreted from ADSCs both as diagnostic biomarkers and therapeutics in diabetes and associated cardiovascular disease, the molecular mechanisms involved, as well as on the use of ADSC differentiation potential in cardiovascular tissue repair and prostheses. [ABSTRACT FROM AUTHOR]

(1) Background: Ovarian tissue transplantation with adipose tissue-derived stem cells (ASCs) has been shown to enhance graft vascularization and increase follicle survival after a short interval of 7 days. The aim of the present study was to investigate their long-term effects on primordial follicle pool maintenance and follicle development. (2) Methods: A total of 14 severe combined immunodeficient (SCID) mice were grafted with frozen-thawed human ovarian tissue with or without ASCs. Blood was taken monthly in order to quantify the anti-Müllerian hormone (AMH) and estradiol. After 6 months, all the grafts were retrieved and sent for histology and immunolabeling (AMH, AMH receptor II, estrogen receptors α and β, and c-kit/kit ligand). (3) Results: A significant upturn was observed in AMH and estradiol plasma levels 4 months after transplantation in both grafted groups. The primordial follicle pool was better preserved in the ASC group (41.86 ± 28.35) than in the standard transplantation group (9.65 ± 17.6, p < 0.05) compared to non-grafted controls (124.7 ± 140). (4) Conclusions: The use of ASCs prior to ovarian tissue transplantation yielded a larger primordial follicle pool and more physiological follicle distribution after long-term grafting. These findings suggested that ASC use might extend the ovarian tissue lifespan. [ABSTRACT FROM AUTHOR]

Wound healing is a complex process with a linear development that involves many actors in a multistep timeline commonly divided into four stages: Hemostasis, inflammation, proliferation, and remodeling. Chronic non-healing wounds fail to progress beyond the inflammatory phase, thus precluding the next steps and, ultimately, wound repair. Many intrinsic or extrinsic factors may contribute to such an occurrence, including patient health conditions, age-related diseases, metabolic deficiencies, advanced age, mechanical pressure, and infections. Great interest is being focused on the adipose tissue-derived stem cell's (ASC) paracrine activity for its potential therapeutic impact on chronic non-healing wounds. In this review, we summarize the results of in vitro and in vivo experimental studies on the pro-wound healing effects of ASC-secretome and/or extracellular vesicles (EVs). To define an overall picture of the available literature data, experimental conditions and applied methodologies are described as well as the in vitro and in vivo models chosen in the reported studies. Even if a comparative analysis of the results obtained by the different groups is challenging due to the large variability of experimental conditions, the available findings are undoubtedly encouraging and fully support the use of cell-free therapies for the treatment of chronic non-healing wounds. [ABSTRACT FROM AUTHOR]

The purpose of this study was to conduct a histomorphometric analysis of bone marrow-derived and adipose tissue-derived stem cells, associated with a xenograft block, in vertical bone constructions in rabbit calvaria. Ten rabbits received two xenograft blocks on the calvaria, after decortication of the parietal bone. The blocks were fixed with titanium screws. The blocks were combined with the bone marrow-derived mesenchymal stem cells in the bone marrow stem cell (BMSC) group (right side of the calvaria) or with the adipose tissue-derived mesenchymal stem cells in the adipose tissue stem cell (ATSC) group (left side of the calvaria). After 8 weeks, the animals were sacrificed and their parietal bones were fixed in 10% formalin for the histomorphometric analysis. The following parameters were evaluated—newly formed bone (NFB), xenogeneic residual particles (XRP), and non-mineralized tissue (NMT). The histomorphometric analysis revealed 11.9 ± 7.5% and 7.6 ± 5.6% for NFB, 22.14 ± 8.5% and 21.6 ± 8.5% for XRP, and 65.8 ± 10.4% and 70.8 ± 7.4% for NMT in groups BMSC and ATSC, respectively, with statistically significant differences in the NFB and the NMT between the groups, but no differences in the XRP. Therefore, it can be concluded that the bone marrow-derived stem cells seem to have more potential for the bone formation than do the adipose tissue-derived stem cells when used in combination with the xenogenous blocks in the vertical bone construction. [ABSTRACT FROM AUTHOR]

Adipose tissue-derived stem cells (ASCs) in the form of stromal vascular fraction (SVF) and cultured expansion have been applied in clinical settings in some countries to treat osteoarthritis (OA) of knees, one of the most common debilitating, incurable disorders. Since the first report of successful cartilage-like tissue regeneration with autologous adipose SVF containing ASCs, there has been a gradual increase in the number of publications confirming such results. Thus far, most of the reports have been limited to treatments of OA of knees. Recently, successful applications of adipose SVF in treating OA of ankles and hips have been reported. In addition, several groups have reported modified methods of applying adipose SVF, such as combining bone marrow stimulation with adipose SVF or adding additional extracellular matrix (ECM) in treating OA. Here, we present an updated, systematic review of clinical effectiveness and safety in treating OA of knees, ankles, and one hip since 2016 using ASCs in the form of adipose SVF or in cultured expansion, along with a description and suggestion of potential biological mechanisms of cartilage regeneration. [ABSTRACT FROM AUTHOR]