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BACKGROUND: Infant adipose-derived mesenchymal stem cells (ADSCs) collected from excised polydactyly fat tissue, which was surgical waste, could be cultured and expanded in vitro in this study. In addition, the collecting process would not cause pain in the host. In this study, the proliferation, reduction of senescence, anti-oxidative ability, and differentiation potential in the infant ADSCs were compared with those in the adult ADSCs harvested from thigh liposuction to determine the availability of infant ADSCs. METHODS: Proliferation was determined by detecting the fold changes in cell numbers and doubling time periods. Senescence was analyzed by investigating the age-related gene expression levels and the replicative stress. The superoxide dismutase (SOD) gene expression, adipogenic, neurogenic, osteogenic, and tenogenic differentiation were compared by RT-qPCR. The chondrogenic differentiation efficiency was also determined using RT-qPCR and immunohistochemical staining. RESULTS: The proliferation, SOD (SOD1, SOD2 and SOD3) gene expression, the stemness-related gene (c-MYC) and telomerase reverse transcriptase of the infant ADSCs at early passages were enhanced compared with those of the adults'. Cellular senescence related genes, including p16, p21 and p53, and replicative stress were reduced in the infant ADSCs. The adipogenic genes (PPARγ and LPL) and neurogenic genes (MAP2 and NEFH) of the infant ADSC differentiated cells were significantly higher than those of the adults’ while the expression of the osteogenic genes (OCN and RUNX) and tenogenic genes (TNC and COL3A1) of both demonstrated opposite results. The chondrogenic markers (SOX9, COL2 and COL10) were enhanced in the infant ADSC differentiated chondrogenic pellets, and the expression levels of SODs were decreased during the differentiation process. CONCLUSION: Cultured infant ADSCs demonstrate less cellular senescence and replicative stress, higher proliferation rates, better antioxidant defense activity, and higher potential of chondrogenic, adipogenic and neurogenic differentiation. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13770-022-00431-x.

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) is a novel coronavirus that infects many types of cells and causes cytokine storms, excessive inflammation, acute respiratory distress to induce failure of respiratory system and other critical organs. In this study, our results showed that trimethylamine-N-oxide (TMAO), a metabolite generated by gut microbiota, acts as a regulatory mediator to enhance the inerleukin-6 (IL-6) cytokine production and the infection of human endothelial progenitor cells (hEPCs) by SARS-CoV-2. Treatment of N-3 polyunsaturated fatty acids (PUFAs) such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) could effectively block the entry of SARS-CoV-2 in hEPCs. The anti-infection effects of N-3 PUFAs were associated with the inactivation of NF-κB signaling pathway, a decreased expression of the entry receptor angiotensin-converting enzyme 2 (ACE2) and downstream transmembrane serine protease 2 in hEPCs upon the stimulation of TMAO. Treatment of DHA and EPA further effectively inhibited TMAO-mediated expression of IL-6 protein, probably through an inactivation of MAPK/p38/JNK signaling cascades and a downregulation of microRNA (miR)-221 in hEPCs. In conclusion, N-3 PUFAs such as DHA and EPA could effectively act as preventive agents to block the infection of SARS-CoV-2 and IL-6 cytokine production in hEPCs upon the stimulation of TMAO.

A PEEK button is developed to improve the tendon-to-bone compression area. In total, 18 goats were divided into 12-week, 4-week, and 0-week groups. All underwent bilateral detachment of the infraspinatus tendon. In the 12-week group, 6 were fixed with a 0.8–1 mm-thick PEEK augment (A-12, Augmented), and 6 were fixed with the double-row technique (DR-12). Overall, 6 infraspinatus were fixed with PEEK augment (A-4) and without PEEK augment (DR-4) in the 4-week group. The same condition was performed in the 0-week groups (A-0 and DR-0). Mechanical testing, immunohistochemistry assessment, cell responses, tissue alternation, surgical impact, remodeling, and the expression of type I, II, and III collagen of the native tendon-to-bone insertion and new footprint areas were evaluated. The average maximum load in the A-12 group (393.75 (84.40) N) was significantly larger than in the TOE-12 group (229.17 (43.94) N) (p < 0.001). Cell responses and tissue alternations in the 4-week group were slight. The new footprint area of the A-4 group had better fibrocartilage maturation and more type III collagen expression than in DR-4 group. This result proved the novel device is safe and provides superior load-displacement to the double-row technique. There is a trend toward better fibrocartilage maturation and more collagen III secretions in the PEEK augmentation group.

Repairing the peripheral nerves following a segmental defect injury remains surgically challenging. Because of some disadvantages of nerve grafts, nerve regeneration, such as conduits combined with bone marrow-derived mesenchymal stem cells (BMSCs), may serve as an alternative. BMSCs expand under hypoxic conditions, decrease in senescence, and increase in proliferation and differentiation potential into the bone, fat, and cartilage. The purpose of this study was to investigate whether BMSCs increased the neuronal differentiation potential following expansion under hypoxic conditions. Isolated human BMSCs (hBMSCs) expand under hypoxia or normoxia, and neuronal differentiation proceeds under normoxia. in vitro tests revealed hypoxia culture enhanced the RNA and protein expression of neuronal markers. The electrophysiology of hBMSC-differentiated neuron-like cells was also enhanced by the hypoxia culturing. Our animal model indicated that the potential treatment of hypoxic rat BMSCs (rBMSCs) was better than that of normoxic rBMSCs because the conduit with the hypoxic rBMSCs injection demonstrated the highest recovery rate of gastrocnemius muscle weights. There were more toluidine blue-stained myelinated nerve fibers in the hypoxic rBMSCs group than in the normoxic group. To sum up, BMSCs cultured under hypoxia increased the potential of neuronal differentiation both in vivo and in vitro.

The purpose of this study was to clinically validate the Hill–Sachs interval to glenoid track width ratio (H/G ratio) compared with the instability severity index (ISI) score for predicting an increased risk of recurrent instability after arthroscopic Bankart repair. A retrospective evaluation was performed using data from patients with anteroinferior shoulder instability who underwent arthroscopic Bankart repair with a follow-up period of at least 24 months. A receiver operating characteristic (ROC) curve was used to determine the optimal cut-off values for the H/G ratio and the ISI score to predict an increased risk of recurrent instability. The area under the ROC curve (AUC) of the two methods and the sensitivity and specificity of their optimal cut-off values were compared. A total of 222 patients were included, among whom 31 (14.0%) experienced recurrent instability during the follow-up period. The optimal cut-off values for predicting an increased risk of recurrent instability were an H/G ratio of ≥ 0.7 and ISI score of ≥ 4. There were no significant differences between the AUC of the two methods (H/G ratio AUC = 0.821, standard error = 0.035 and ISI score AUC = 0.792, standard error = 0.04; n.s.) nor between the sensitivity and specificity of the optimal cut-off values (n.s. and n.s., respectively). The H/G ratio is comparable to the ISI score for predicting an increased risk of recurrent instability after arthroscopic Bankart repair. Surgeons are recommended to consider other strategies to treat anterior shoulder instability if H/G ratio is ≥ 0.7. III.

Adipose-derived mesenchymal stem cells (ADSCs), which tended to neurogenically differentiate spontaneously after achieving high confluence, were observed. Human ADSCs reaching 80% confluence were cultured in DMEM without an inducing factor for 24 hr and then maintained in DMEM plus 1% FBS medium for 7 days. The neurogenic, adipogenic, and osteogenic genes of the factor-induced and confluence-initiated differentiation of the ADSCs and bone marrow-derived mesenchymal stem cells (BMSCs) at passages 3 to 5 were determined and compared using RT-qPCR, and the neurogenic differentiation was confirmed using immunofluorescent staining. In vitro tests revealed that the RNA and protein expression of neuronal markers, including class Ⅲ β-tubulin (TUBB3), microtubule-associated protein 2 (MAP2), neurofilament medium polypeptide (NEFM), neurofilament heavy polypeptide (NEFH), and neurofilament light polypeptide (NEFL), had been enhanced in the confluence-initiated differentiation of the ADSCs. In addition, the expressions of neurotrophins, such as the nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and glial cell-derived neurotrophic factor (GDNF), were also elevated in the confluence-initiated differentiation of the ADSCs. However, the confluent ADSCs did not show a tendency toward spontaneous adipogenic and osteogenic differentiation. Moreover, compared with the confluent ADSCs, the tendency of spontaneous neurogenic, adipogenic, and osteogenic differentiation of the confluent human bone marrow mesenchymal stem cells (BMSCs) was not observed. The results indicated that ADSCs had the potential to spontaneously differentiate into neuron-like cells during the confluent culture period, however, this tendency was not observed in BMSCs.

Background:Several surgical techniques have been proposed for massive rotator cuff tears (MRCTs), but the failure rates remain high. The suture-spanning augmentation technique of single-row (SSA-SR) repair was shown to reduce failure rates in cadaveric studies, but the outcome in vivo remains unclear.Purpose:To determine if adding spanning sutures to SR repair during MRCT repairs can improve functional outcome and reduce failure rates.Study Design:Randomized controlled trial; Level of evidence, 2.Methods:The study included 71 patients with a diagnosed MRCT. The study group (n = 35) received SSA-SR repair. The control (n = 36) received SR repair. The American Shoulder and Elbow Surgeons (ASES) score, Constant score, UCLA (University of California, Los Angeles) score, and visual analog scale for pain were assessed preoperatively and 24 months postoperatively. Magnetic resonance imaging was arranged at 6 months postoperatively to evaluate the rotator cuff.Results:At 6 months postoperatively, the overall retear rate was 31.0%. The retear rate was lower in the SSA-SR group (14.3%) than in the SR group (47.2%, P = .002). At 24 months, the SSA-SR group had markedly improved ASES, Constant, and UCLA scores in comparison with the SR group ( P < .05). Within both groups, all scores had significant improvement as compared with the preoperative status ( P < .05).Conclusion:The SSA-SR repair technique showed improved functional and radiologic results. Based on the superior postoperative outcome of this technique, the SSA-SR repair technique can be a potential treatment option for MRCT repair.Registration:NCT03609164 (ClinicalTrials.gov identifier).

Purpose To investigate the tunnel enlargement rate and clinical function by comparing double-bundle anterior cruciate ligament reconstruction (ACLR) using different fixation devices. Methods Patients receiving primary arthroscopic double-bundle ACLR were screened and divided into 2 groups on the basis of the method of graft fixation: bioabsorbable interference screw (BS) group and cortical button (CB) group. Bone tunnel size was assessed digitally using magnetic resonance imaging, which was performed a minimum of 2 years postoperatively. Clinical evaluations were performed using the Knee Injury and Osteoarthritis Outcome Score, International Knee Documentation Committee score, and KT-1000 arthrometer 2 years postoperatively. Results Sixty patients receiving primary arthroscopic double-bundle ACLR were included. Overall, the BS group showed greater tunnel enlargement than the CB group, as well as a significantly increased rate of tunnel communication (P = .029). The average anteromedial tunnel enlargement rates for the BS and CB groups were 50% and 28%, respectively. The enlargement rate of the posterolateral (PL) femoral tunnel was similar in both groups. In the PL tibial tunnel, the CB group showed a significant increase in enlargement compared with the BS group (64% vs 45%, P = .0001). Both groups showed functional improvement in the Knee Injury and Osteoarthritis Outcome Score and International Knee Documentation Committee score. No significant difference in postoperative functional outcomes was found between the 2 groups. Conclusions The BS group showed significantly greater tunnel enlargement in anteromedial tunnels and an increased tunnel communication rate compared with the CB group. On the other hand, the CB group showed greater tunnel enlargement in tibial PL tunnels. Tunnel communication was observed mostly on the tibial side in the BS patients. Equivalent clinical function outcomes were noted at 2 years after surgery in both groups of patients. Level of Evidence Level II, randomized controlled clinical trial.

PURPOSE To assess the failure rate and clinical outcomes of the all-inside double vertical cross-suture technique in repairing complete radial tears of the lateral meniscus. METHOD We retrospectively reviewed records of patients with this injury on whom the present technique was employed at our institution between 2011 and 2018 with at least 24 months of follow-up. Six months postoperatively, the meniscus healing and extrusion status were evaluated through magnetic resonance imaging. Preoperative and postoperative knee function, measured through IKDC, Lysholm knee, and Tegner activity scale scores, were compared RESULTS: In total, 27 patients underwent the procedure. The preoperative mean (standard deviation) IKDC score, Lysholm knee score, and Tegner activity scale scores were 53.4 ± 5.3, 63.2 ± 9.3, and 4 ± 0.7, respectively. At the last follow-up (≥24 months postoperatively), these scores increased to 92.1 ± 2.6, 90.8 ± 4.2, and 6.1 ± 1.3, respectively (all (P < .05). Complete healing of the meniscus was observed in 23 patients, and 4 patients had meniscus retear or nonhealing. The overallretear or nonhealing rate was 14.8%. . Healing rates between those with isolated radial tears (87.5%) and those with combined anterior cruciate ligament rupture (84.2%; P = .826) were comparable. No difference was observed in the progression of coronal and sagittal meniscus extrusion (P = .133 and .797, respectively). CONCLUSION In patients with complete radial tears of the lateral meniscus, the arthroscopic all-inside double vertical cross-suture repair technique resulted in an 85.2% healing rate, improvements in functional outcomes and activity levels, and no identifiable progression of meniscus extrusion. The all-inside double vertical cross-suture technique is effective and safe for the repair of radial tears of the meniscus.

The method to benifit tissue engineering of adipose-derived stem cells (ADSCs) to cartilage has been an objective of intense research in treating increasing cartilage-related disease. In this study, whether hypoxic expansion would enhance the proliferation and in vitro chondrogenic differentiation of ADSCs was studied, and then hypoxic expansion was applied to reduce cartilage damage in a rat model in vivo. Hypoxic expansion increased the proliferation and decreased the expression of aging-related genes, including p16, p21, and p53, of human ADSCs in comparison with normoxic expansion. In addition, the γH2AX expression was reduced in the hypoxic ADSCs. The chondrogenic markers were enhanced in the hypoxic ADSC differentiated chondrogenic pellets, including SOX9 on day 7 and gene expressions of COL 2 and COL 10 on day 21. To determine the in vitro chondrogenic differentiation potential of ADSCs, ADSC differentiated 21-day chondrogenic pellets were stained by Alcian blue staining and the immunostaining of COL 2 and COL 10, the results of which confirmed the enhancement of differentiation potential after the hypoxic expansion. Moreover, cartilage injury in a rat model was reduced by hypoxic ADSC treatment that was determined by histological and immunohistochemical staining detections. The effects of hypoxic expansion of ADSCs and bone marrow-derived stem cells (BMSCs) on chondrogenic differentiation potential were also compared. Smaller sizes were presented in the in vitro hypoxic BMSC differentiated chondrogenic pellets, whereas the chondrogenic marker expressions were significantly higher than those of the hypoxic ADSCs. However, there was no significant difference between the treatments of the hypoxic ADSCs and BMSCs in the cartilage injury in vivo. In conclusion, hypoxic expansion increases the chondrogenic differentiation potential of ADSCs and BMSCs in vitro and enhances them to reduce cartilage damage in vivo. Although the hypoxic BMSCs showed compact chondrogenic pellet formation and higher potential of chondrogenesis, the easy access and large resources of ADSCs still uplifted the application.

Tranexamic acid (TXA) has been administrated in many orthopaedic surgical procedures to decrease perioperative and postsurgical bleeding. Relatively scant literature exists regarding the effect of TXA in patients after anterior cruciate ligament reconstruction. Currently, most evidence shows that within about 1 month after anterior cruciate ligament reconstruction, TXA can effectively reduce postoperative joint swelling and pain, as well as the aspiration rate. However, there are still controversies regarding the optimal dosage, timing, and route of administration of TXA in these patients. In addition, the potential chondrotoxic effect of TXA needs to be further clarified with longer clinical follow-up.

The purpose of this study was to clinically validate the Hill-Sachs interval to glenoid track width ratio (H/G ratio) compared with the instability severity index (ISI) score for predicting an increased risk of recurrent instability after arthroscopic Bankart repair.A retrospective evaluation was performed using data from patients with anteroinferior shoulder instability who underwent arthroscopic Bankart repair with a follow-up period of at least 24 months. A receiver operating characteristic (ROC) curve was used to determine the optimal cut-off values for the H/G ratio and the ISI score to predict an increased risk of recurrent instability. The area under the ROC curve (AUC) of the two methods and the sensitivity and specificity of their optimal cut-off values were compared.A total of 222 patients were included, among whom 31 (14.0%) experienced recurrent instability during the follow-up period. The optimal cut-off values for predicting an increased risk of recurrent instability were an H/G ratio of ≥ 0.7 and ISI score of ≥ 4. There were no significant differences between the AUC of the two methods (H/G ratio AUC = 0.821, standard error = 0.035 and ISI score AUC = 0.792, standard error = 0.04; n.s.) nor between the sensitivity and specificity of the optimal cut-off values (n.s. and n.s., respectively).The H/G ratio is comparable to the ISI score for predicting an increased risk of recurrent instability after arthroscopic Bankart repair. Surgeons are recommended to consider other strategies to treat anterior shoulder instability if H/G ratio is ≥ 0.7.III.

The incidence of meniscal tear was reported to increase with the delay of anterior cruciate ligament reconstruction (ACLR). The tear may occur concurrently with the ACL injury or after the ACL injury. Few studies had focused on the patients whose meniscus is intact during ACL injury. We determined the correlation between timing of surgery and incidence of meniscal tears in ACL-deficient knees with initially intact meniscus. We retrospectively reviewed 387 patients who had undergone primary ACLR. Time of initial ACL injury, magnetic resonance imaging (MRI) examination, and surgery was recorded. The MRI was reviewed by experienced radiologic and orthopaedic doctors. Intraoperative arthroscopic images were also obtained and reviewed. The type of tear noted during surgery was classified according to the modification of International Society of Arthroscopy, Knee Surgery and Orthopaedic Sports Medicine classification of meniscal tears. Patients were divided into early (surgery within 12 months from injury) and late surgery group (surgery at more than 12 months from injury). There were 216 patients with intact medial meniscus and 257 patients with intact lateral meniscus on the postinjury MRI study. The incidence of medial meniscus tear (MMT) was significantly higher than lateral meniscus tear (LMT) during the ACLR (33.8 vs. 19.8%, p

To evaluate the effect of intra-articular injection of tranexamic acid (TXA) in patients receiving arthroscopic anterior cruciate ligament reconstruction (ACLR).A total of 304 patients were included in this study, which was performed between August 2017 and April 2018. Single-bundle reconstructions using autologous hamstring tendon grafts were performed in all patients. Patients were randomized into 2 groups: Group 1 patients (TXA group) received the index procedure with a 10-mL intra-articular injection of TXA (100 mg/mL). Group 2 patients (control group) received the index procedure without TXA injections. An intra-articular suction drain was placed in the joint and clamped for 2 hours after the procedure. The volume of drainage was recorded 24 hours after surgery. Clinical evaluations using the International Knee Documentation Committee functional score, range of motion, and a visual analog scale pain score were performed on day 3 and at week 4 postoperatively.Twenty-four hours after surgery, a significant decrease in the amount of drainage was observed in patients receiving intra-articular injections (TXA group, 56.1 ± 34.1 mL; control group, 80.1 ± 48 mL; P.05). On day 3 and at week 4, significantly reduced pain scores were reported in the TXA group. However, at week 4, clinical function scores did not show significant differences between the 2 groups.Intra-articular injection of TXA could significantly reduce postoperative intra-articular bleeding in the first 24 hours in patients receiving arthroscopic ACLR. TXA injection may also decrease pain and the grade of hemarthrosis in the early postoperative period. No systemic side effects or need for aspiration was noted during the follow-up period. Therefore, intra-articular injection of TXA could be considered an effective and relatively safe solution to reduce postoperative bleeding and pain in ACLR patients.Level II, prospective comparative study.

Intervertebral discs (IVDs) are important biomechanical components of the spine. Once degenerated, mesenchymal stem cell (MSC)-based therapies may aid in the repair of these discs. Although hypoxic preconditioning enhances the chondrogenic potential of MSCs, it is unknown whether bone marrow MSCs expanded under hypoxic conditions (1% O2 , here referred to as hypoxic MSCs) are better than bone marrow MSCs expanded under normoxic conditions (air, here referred to as normoxic MSCs) with regards to disc regeneration capacity. The purpose of this study was to compare the therapeutic effects of hypoxic and normoxic MSCs in a rabbit needle puncture degenerated disc model after intra-disc injection. Six weeks after needle puncture, MSCs were injected into the IVD. A vehicle-treated group and an un-punctured sham-control group were included as controls. The tissues were analyzed by histological and immunohistochemical methods 6 and 12 weeks post-injection. At 6 and 12 weeks, less disc space narrowing was evident in the hypoxic MSC-treated group compared to the normoxic MSC-treated group. Significantly better histological scores were observed in the hypoxic MSC group. Discs treated with hypoxic MSCs also demonstrated significantly better extracellular matrix deposition in type II and XI collagen. Increased CD105 and BMP-7 expression were also observed upon injection of hypoxic MSCs. In conclusion, hypoxic MSC injection was more effective than normoxic MSC injection for reducing IVD degeneration progression in vivo. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1440-1450, 2019.

Pigmented villonodular synovitis (PVNS) is a benign tissue proliferation characterized by its hyper-vascularity within the lesion. The true etiology and cell source of this disease entity still remain unclear. Mesenchymal stem cells (MSCs) exist in various tissues of human body. However, it has not been clarified whether MSCs could be isolated from tissue of PVNS. Here, we isolated MSCs from PVNS (PVNS-SCs), and by comparing to the MSCs from normal synovium (Syn-SCs) of the same individual, we investigated whether PVNS-SCs differed in the capacity for multi-differentiation and inducing angiogenesis. We first demonstrated that PVNS-SCs existed in the lesion of PVNS of three individuals. Moreover, we showed PVNS-SCs had better osteogenic differentiation potential than Syn-SCs, whereas Syn-SCs had better capacity for adipogenic and chondrogenic differentiation. By genome-wide analysis of gene expression profile using a complementary DNA microarray and comparing to Syn-SCs, we identified in PVNS-SCs a distinct gene expression profile characterized by up-regulation of genes involved in angiogenesis. In vitro and in vivo studies further confirmed that PVNS-SCs had better capacities for promoting angiogenesis. In summary, the identification of PVNS-SCs in PVNS tissue and their distinct angiogenic potential may help elucidate the underlying etiology of this disease.

Introduction The glenoid track concept was used to confirm the engaging Hill–Sachs lesion (HSL) as a risk factor for recurrent instability following arthroscopic Bankart repair (ABR). However, the post-operative condition of soft tissue in vivo was not comparable to that designed in the intact condition in vitro in the original study of the glenoid track concept. Herein, the possibility of engagement may be underestimated. Hypothesis A threshold of the Hill–Sachs interval to glenoid track width ratio (H/G ratio) that is related to recurrent instability after ABR could be found, in order to adjust the original glenoid track concept. Patients and methods Patients who underwent ABR with minimum 24-months follow-up were reviewed retrospectively. The primary outcome was evaluated with the recurrent instability. The H/G ratio of individual patients was used to calculate the sensitivity, specificity, and a receiver operating characteristic (ROC) curve, which aimed to establish a H/G ratio threshold related to recurrent instability after ABR. Results From June 2005 to December 2013, 160 patients with a mean age of 27.7 years were enrolled. The mean follow-up period was 77.2 months. The ROC curve indicated that H/G ratio≥ 0.7 had the sensitivity and specificity of 0.74 and 0.71, respectively, in predicting recurrent instability. On univariate logistic regression analysis, the H/G ratio≥ 0.7 was a significant predictor of higher risk for recurrent instability (p Discussion H/G ratio seems to be a reliable parameter for predicting recurrent instability. H/G ratio ≥ 0.7 may be considered as a positive predictor for recurrent instability after ABR. Level of evidence Level IV: retrospective diagnostic study.

The self-healing potential of each tissue belongs to endogenous stem cells residing in the tissue; however, there are currently no reports mentioned for the isolation of human rotator cuff-derived mesenchymal stem cells (RC-MSCs) since. To isolate RC-MSCs, minced rotator cuff samples were first digested with enzymes and the single cell suspensions were seeded in plastic culture dishes. Twenty-four hours later, nonadherent cells were removed and the adherent cells were further cultured. The RC-MSCs had fibroblast-like morphology and were positive for the putative surface markers of MSCs, such as CD44, CD73, CD90, CD105, and CD166, and negative for the putative markers of hematopoietic cells, such as CD34, CD45, and CD133. Similar to BM-MSCs, RC-MSCs were demonstrated to have the potential to undergo osteogenic, adipogenic, and chondrogenic differentiation. Upon induction in the defined media, RC-MSCs also expressed lineage-specific genes, such as Runx 2 and osteocalcin in osteogenic induction, PPAR-γ and LPL in adipogenic differentiation, and aggrecan and Col2a1 in chondrogenic differentiation. The multipotent feature of RC-MSCs in the myogenic injury model was further strengthened by the increase in myogenic potential both in vitro and in vivo when compared with BM-MSCs. These results demonstrate the successful isolation of MSCs from human rotator cuffs and encourage the application of RC-MSCs in myogenic regeneration.

This study aimed to evaluate the clinical outcomes of irreparable rotator cuff tears (RCT) treated with an arthroscopic partial repair, as well as the preoperative factors that may be related to greater improvement of clinical outcomes at short-term follow-up.We retrospectively reviewed patients with irreparable RCT who underwent arthroscopic partial rotator cuff repair between January 2011 and April 2014. Minimal follow-up of 24 months was required. Partial repair was defined as repairing the less retracted posterosuperior rotator cuff with a residual defect of the tendon-footprint junction. Tearing involving the subscapularis tendon was excluded. Factors collected included age, sex, diabetes, smoking, night pain, duration of symptoms, pain visual analog scale (VAS) score, acromiohumeral distance (AHD), and American Shoulder and Elbow Surgeons (ASES) score. Magnetic resonance images without intra-articular contrast were assessed for healing 6 months after surgery for all patients. Functional outcome was evaluated with ASES score. Degree of functional improvement was defined as the difference of ASES scores pre- and postoperatively (d-ASES). Paired t-test and simple linear analysis were used for statistical analysis.Thirty-seven patients were included with a mean follow-up period of 29.6 ± 6.6 months. VAS score improved from 5.22 to 1.51 (P.001). ASES score improved from 46.0 to 78.6 (P.001). The incidence of night pain improved from 70.3% to 8.1% (P.001). Only a preoperative lower ASES score, higher VAS score, and night pain were related to the higher d-ASES score (P.001, P = .005, P = .017, respectively). The rate of repair failure was 41.6% at a mean follow-up of 6.4 months.Arthroscopic partial repair of irreparable RCTs is an effective treatment to improve the shoulder function and decrease the pain, despite the high repair failure rate of 41.6%. Patients with preoperative lower functional score, higher VAS score, or night pain experienced a greater degree of functional improvement from the surgery. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

The use of hamstring tendon autografts for anterior cruciate ligament (ACL) surgery has become more and more common. The purposes of this study were to determine whether anthropomorphic measurement correlated with tendon sizes in Chinese patient group and whether tendon sizes in Chinese and Caucasian patient groups differed. From 2008 to 2009, 100 patients that received double-bundle ACL reconstruction with autologous hamstring tendons were prospectively enrolled. The original lengths and triple-folded graft diameters of the individual semitendinosus (ST) and gracilis (Gr) tendons were recorded and correlated with the anthropometric data (height, weight, body mass index, gender, thigh length, shank length, leg length and bilateral thigh circumference) of the patients. Later, using height for predictions, the original heights of patients were added to the equations previously used for regression models to compare the tendon lengths in different ethnic groups. After stepwise multiple linear regression analysis, the height and leg lengths showed greatest correlation with the lengths of both tendons. The lengths of both the semitendinosus and gracilis tendons in Caucasian patients were significantly longer than in the Chinese patients. The results of this study showed that anthropomorphic measurements (height and leg length) correlated with tendon lengths. In addition, Caucasians had significantly longer hamstring tendons than the Chinese patients. Prospective cohort study (prevalence), Level I.

Palmar fibromatosis is a benign fibroproliferative tumor of unknown etiology, with a high rate of recurrence after excision. The offending cells of palmar fibromatosis are myofibroblasts and the cellular origin of other myofibroblasts has previously been reported to be the bone marrow. However, further clarification of the relationship between bone marrow precursors and palmar fibromatosis is required. Stem cells (SCs) are known to exist in various tissues, but whether SCs can be isolated from fibromatosis tissue is still unclear. The purpose of this study was to isolate and identify stem cells from human palmar fibromatosis, and to evaluate the differences in the differentiation and fibrogenic capacities of bone marrow stem cells (BMSCs) and fibromatosis-derived stem cells (FSCs). We found that FSCs had better fibrogenic differentiation potential than BMSCs, whereas BMSCs had better adipogenic and chondrogenic differentiation capacities. Treatment with transforming growth factor-β1 increased the expression of α-smooth muscle actin, and types III and I collagen significantly more in FSCs than in BMSCs. An in vivo study further confirmed the results of fibrogenesis and suggested that FSCs can recapitulate the fibromatosis nodule. In summary, their myofibroblastic differentiation both in vivo and in vitro makes FSCs a potential cell source for future applications in murine models of fibromatosis or fibrogenesis.

Trichostatin A (TSA) is a histone deacetylase inhibitor (HDACi) known to modulate differentiation of many cells. However, its effect on chondrogenesis remains elusive. This study was aimed to investigate the effects of TSA on in vitro transforming growth factor-β1 (TGF-β1)-induced chondrogenesis of human mesenchymal stem cells (hMSCs). The pellet cultures of hMSCs in a chondrogenic medium were exposed to TGF-β1 and TSA. Quantitative reverse transcription/polymerase chain reaction (PCR) analysis, Alcian blue staining, and immunohistochemistry staining were used to confirm and compare the differences in chondrogenesis by analyzing the mRNA of chondrogenic genes (Sox9, Aggrecan, and Col2A1), synthesis of chondrogenic proteins and type II collagen, respectively. TGF-β1 signaling and its downstream targets were determined by western blot analysis. TGF-β1 led to significant increases in chondrogenic gene expression and the synthesis of chondrogenic proteins. However, TSA significantly decreased chondrogenic gene expression and the synthesis of chondrogenic proteins in a dose-dependent manner. TGF-β1 increased phosphorylation of Smad 2/3 and Sp1 expression around half an hour after induction. The increase of Sp1, but not Smad 2/3 activation was almost completely blocked by the addition of TSA. The chondrogenic effect of TGF-β1 was also suppressed by the Sp1-binding inhibitor mithramycin A. Finally, overexpression of Sp1 abolished TSA-mediated inhibition of TGF-β1-induced chondrogenesis. Our study showed that TSA inhibited chondrogenesis through inhibition of TGF-β1-induced Sp1 expression. Furthermore, Sp1 could be a useful tool in future studies looking into biological mechanisms by which chondrogenesis of hMSCs can be augmented, especially in the area of clinical application.

Introduction The glenoid track concept was used to confirm the engaging Hill–Sachs lesion (HSL) as a risk factor for recurrent instability following arthroscopic Bankart repair (ABR). However, the post-operative condition of soft tissue in vivo was not comparable to that designed in the intact condition in vitro in the original study of the glenoid track concept. Herein, the possibility of engagement may be underestimated. Hypothesis A threshold of the Hill–Sachs interval to glenoid track width ratio (H/G ratio) that is related to recurrent instability after ABR could be found, in order to adjust the original glenoid track concept. Patients and methods Patients who underwent ABR with minimum 24-months follow-up were reviewed retrospectively. The primary outcome was evaluated with the recurrent instability. The H/G ratio of individual patients was used to calculate the sensitivity, specificity, and a receiver-operating characteristic (ROC) curve, which aimed to establish a H/G ratio threshold related to recurrent instability after ABR. Results From June 2005 to December 2013, 160 patients with a mean age of 27.7 years were enrolled. The mean follow-up period was 77.2 months. The ROC curve indicated that H/G ratio ≥ 0.7 had the sensitivity and specificity of 0.74 and 0.71, respectively, in predicting recurrent instability. On univariate logistic regression analysis, the H/G ratio ≥ 0.7 was a significant predictor of higher risk for recurrent instability (p Discussion H/G ratio seems to be a reliable parameter for predicting recurrent instability. H/G ratio ≥ 0.7 may be considered as a positive predictor for recurrent instability after ABR. Level of evidence Level IV: retrospective diagnostic study.

Shoulder joint laxity over anteroinferior and posteroinferior labral–capsular structure inpatients with traumatic anterior glenohumeral instability was reported in the previous literature. The purpose of this study was to report our experience in arthroscopic treatment of traumatic anterior–inferior shoulder instability by Bankart lesion stabilisation with rotator interval closure and posteroinferior capsular plication.From August 2000 to November 2004, 45 patients with traumatic anterior–inferior shoulder instability were retrospectively enrolled. Each shoulder was treated with absorbable suture for rotator interval closure and posteroinferior capsular plication after anteroinferior stabilisation. The assessments were performed using the Rowe score, the University of California at Los Angeles (UCLA) shoulder rating scale, the American Shoulder and Elbow Surgeons (ASES) score) and shoulder range of motion (ROM).With the average follow-up time of 77.1 months, all shoulder scores improved after surgery(P0.001). The average ROM deficit of the operated shoulders was not significant (P0.05) as compared with the healthy side. A total of 42 shoulders remained stable (93.3%) and there were three recurrences (6.6%). All patients without recurrence returned to their pre-injury levels of athletic activity.In patients with anterior glenohumeral instability, arthroscopic stabilisation of anteroinferior capsulolabral structure with rotator interval closure and posteroinferior capsular plication provided a reasonable result without significant loss of ROM at a minimum follow-up of 5 years.

Treatment for musculoskeletal fibromatosis remains challenging. Surgical excision for fibromatosis is the standard therapy but recurrence remains high. Corticosteroids, an anti-fibrogenic compound, have been used to treat early stage palmar fibromatosis, but the mechanism is unknown. We investigated the inhibitory mechanism effect of corticosteroids in the murine model of fibromatosis nodule as well as in cultured FSCs. Quantitative reverse transcription/polymerase chain reaction (PCR) analysis and immunofluorescence (IF) staining for markers of myofibroblasts (α-smooth muscle actin and type III collagen) were used to examine the effect of dexamethasone on myofibroblasic differentiation of FSCs both in vitro and in vivo. Transforming growth factor-β1 (TGF-β1) signaling and its downstream targets were examined using western blot analysis. TGF-β1 expression in FSCs before and after dexamethasone treatment was compared. In addition, inhibition of TGF-β1 expression was examined using RNA interference (RNAi) on FSCs, both in vitro and in vivo. Treating FSCs with dexamethasone inhibited FSCs' myofibroblastic differentiation in vitro. Treating FSCs with dexamethasone before or after implantation further inhibited formation of fibromatosis nodules. Dexamethasone suppressed expression of TGF-β1 and pSmad2/3 by FSCs in vitro. TGF-β1 knockdown FSCs showed reducing myofibroblastic differentiation both in vitro and in vivo. Finally, addition of TGF-β1 abolished dexamethasone-mediated inhibition of myofibroblastic differentiation. Dexamethasone inhibits the myofibroblastic differentiated potential of FSCs both in vitro and in vivo through inhibition of TGF-β1 expression in FSCs. TGF-β1 plays a key role in myofibroblastic differentiation.

To report a rare case of retroperitoneal schwannoma from lumbar nerve root with difficult surgery and potential vascular complication.We report a rare case of giant schwannoma which arises from fifth lumbar root with L5 vertebral body destruction. Retroperitoneal schwannomas are rare, and those with bony involvement are even rarer and may be mimicking malignant tumors.Retroperitoneal removal of the tumor with partial killing of right L5 nerve root and allograft of L5 vertebral body defect were performed. Incidental injury of common iliac vein was encountered due to adhesion of the vein to tumor capsule. The laceration was repaired by cardiovascular surgeon.At final follow-up, the patient had mild weakness of dorsi-flexion of right ankle and mild right L5 dermatome numbness. No walking difficulty and no sign of local recurrence in the image studies.Retroperitoneal schwannomas are rare, and they can become very large when diagnosed. Major vessels impingement and adhesion can occur which make the surgery difficult. Careful pre-operative evaluation and explanation is very important.

Pigmented villonodular synovitis (PVNS) is a benign tissue proliferation characterized by its hyper-vascularity within the lesion. The true etiology and cell source of this disease entity still remain unclear. Mesenchymal stem cells (MSCs) exist in various tissues of human body. However, it has not been clarified whether MSCs could be isolated from tissue of PVNS. Here, we isolated MSCs from PVNS (PVNS-SCs), and by comparing to the MSCs from normal synovium (Syn-SCs) of the same individual, we investigated whether PVNS-SCs differed in the capacity for multi-differentiation and inducing angiogenesis. We first demonstrated that PVNS-SCs existed in the lesion of PVNS of three individuals. Moreover, we showed PVNS-SCs had better osteogenic differentiation potential than Syn-SCs, whereas Syn-SCs had better capacity for adipogenic and chondrogenic differentiation. By genome-wide analysis of gene expression profile using a complementary DNA microarray and comparing to Syn-SCs, we identified in PVNS-SCs a distinct gene expression profile characterized by up-regulation of genes involved in angiogenesis. In vitro and in vivo studies further confirmed that PVNS-SCs had better capacities for promoting angiogenesis. In summary, the identification of PVNS-SCs in PVNS tissue and their distinct angiogenic potential may help elucidate the underlying etiology of this disease.

Background: Bone marrow–derived mesenchymal stem cells (MSCs) from humans cultured under hypoxic conditions increase bone healing capacity. Hypothesis: Rat MSCs cultured under hypoxic conditions increase the tendon healing potential after transplantation into injured Achilles tendons. Study Design: Controlled laboratory study. Methods: Biomechanical testing, histological analysis, and bromodeoxyuridine (BrdU) labeling/collagen immunohistochemistry were performed to demonstrate that augmentation of an Achilles tendon rupture site with hypoxic MSCs increases healing capacity compared with normoxic MSCs and controls. Fifty Sprague-Dawley rats were used for the experiments, with 2 rats as the source of bone marrow MSCs. The cut Achilles tendons in the rats were equally divided into 3 groups: hypoxic MSC, normoxic MSC, and nontreated (vehicle control). The uncut tendons served as normal uncut controls. Outcome measures included mechanical testing in 24 rats, histological analysis, and BrdU labeling/collagen immunohistochemistry in another 24 rats. Results: The ultimate failure load in the hypoxic MSC group was significantly greater than that in the nontreated or normoxic MSC group at 2 weeks after incision (2.1 N/mm2 vs 1.1 N/mm2 or 1.9 N/mm2, respectively) and at 4 weeks after incision (5.5 N/mm2 vs 1.7 N/mm2 or 2.7 N/mm2, respectively). The ultimate failure load in the hypoxic MSC group at 4 weeks after incision (5.5 N/mm2) was close to but still significantly less than that of the uncut tendon (7.2 N/mm2). Histological analysis as determined by the semiquantitative Bonar histopathological grading scale revealed that the hypoxic MSC group underwent a significant improvement in Achilles tendon healing both at 2 and 4 weeks when compared with the nontreated or normoxic MSC group via statistical analysis. Immunohistochemistry further demonstrated that the hypoxic and normoxic MSC groups had stronger immunostaining for type I and type III collagen than did the nontreated group both at 2 and 4 weeks after incision. Moreover, BrdU labeling of MSCs before injection further determined the incorporation and retention of transplanted cells at the rupture site. Conclusion: Transplantation of hypoxic MSCs may be a better and more readily available treatment than normoxic MSCs for Achilles tendon ruptures. Clinical Relevance: The present study provides evidence that transplantation of hypoxic MSCs may be a promising therapy for the treatment of Achilles tendon ruptures.

Treating shoulder multidirectional instability with an open stabilization procedure has been reported to have good results. However, few studies exist of arthroscopic plication, especially in overhead athletes. The purpose of this study was to evaluate the clinical outcomes of arthroscopic pancapsular plication for multidirectional instability in overhead athletes. Twenty-three athletes with symptomatic multidirectional instability were treated with arthroscopic pancapsular plication and evaluated at a mean follow-up of 36.3 months (range, 24–61 months). Mean patient age was 23.3 years (range, 19–33 years). Functional outcomes were evaluated with the American Shoulder and Elbow Surgeons (ASES) score, Constant shoulder score, and Rowe instability score. The degree of pain and range of motion were also recorded. All postoperative functional scores were rated good to excellent, with an average ASES score of 88.4 (range, 82–95), average Constant shoulder score of 88.1 (range, 81–100), and average Rowe instability score of 86.7 (range, 80–100). Five patients returned to the same level of competitive sports, and 18 returned to a limited level. All patients were satisfied with the stability postoperatively. No significant change was observed in postoperative range of motion, but patients who returned to a limited level of sports had lower functional scores and more pain than did those who fully returned to sports. Arthroscopic pancapsular plication for treating multidirectional instability in overhead athletes can provide good stability. However, the low rate of return to a full level of overhead sports is a problem. Further evaluation of the benefits of this procedure for overhead athletes with symptomatic multidirectional instability is needed.

Introduction The result of treatment of infections involving antibiotic-resistant organisms in total knee arthroplasty (TKA) is often poor. We evaluated the efficacy of 2-stage revision in TKAs infected with resistant organisms and compared the clinical outcomes with articulating and conventional static spacers, in terms of both infection control and function. Methods In a prospective manner, from June 2003 to January 2007 selected patients with a TKA infected with resistant organisms were enrolled and treated with 2-stage re-implantation. The 45 patients were divided into 2 groups: group A (23 patients) implanted with the articulating spacers and group S (22 patients) implanted with static spacers. All patients followed the same antibiotic protocols and had the same re-implantation criteria. The efficacy of infection control was evaluated using re-implantation rate, recurrence rate, and overall success rate. The functional and radiographic results were interpreted with the Hospital of Special Surgery (HSS) knee score and the Insall-Salvati ratio. Results With mean 40 (24–61) months of follow-up, 22 of 23 knees were re-implanted in group A and 21 of 22 were re-implanted in group S. Of these re-implanted prostheses, 1 re-infection occurred in group A and 2 occurred in group S. Range of motion after re-implantation, the final functional scores, and the satisfaction rate were better in group A. One third of the patients in group S, and none in group A, had a patella baja. Interpretation After 2-stage re-implantation of TKAs originally infected with resistant organisms, the clinical outcome was satisfactory—and similar to that reported after treatment of TKAs infected with low-virulence strains. Treatment with an articulating spacer resulted in better functional outcome and lower incidence of patella baja.

Study design To demonstrate the existence of mesenchymal stem cells (MSCs) in ligamentum flavum (LF) and their pathogenic role in LF hypertrophy. Objective To isolate and characterize LF-derived MSCs and their response to transforming growth factor-beta 1 (TGF-β1) and trichostatin A (TSA), a histone deacetylase inhibitor (HDACi). Summary of background data LF is a connective tissue, of which hypertrophic changes induce spinal stenosis. The pathogenic role of TGF-β1 in spinal stenosis has been implicated. TSA has been shown to suppress TGF-β1-induced alpha-smooth muscle actin (α-SMA), type I and III collagen synthesis in a variety of cells. MSCs have been isolated from a variety of adult tissues, except LF. Whether MSCs exist in LF and their response to TGF-β1 and TSA is not clear. Methods The MSCs from LF were isolated and cultured. Their phenotypic character, linage differentiation potential, and response to TGF-β1 and TSA were analyzed. Results LF-derived MSCs have the similar profile of surface markers as bone marrow MSCs. They were demonstrated to have the potential to be differentiated into osteoblasts, adipocytes, and chondrocytes. Administration of TGF-β1 stimulated cell proliferation, enhanced the gene expression of type I and III collagen, and increased the gene expression and protein level of α-SMA. TSA blocked the fibrogenic effects of TGF-β1. Conclusion The current results demonstrated the isolation of MSCs from LF. The cellular response to TGF-β1 implied that these cells might play an important role in the pathogenesis of LF hypertrophy. TSA, which blocks the effects of TGF-β1, may be a potent therapeutic choice for inhibiting LF hypertrophy.

Purpose The purpose of this study was to compare the clinical and imaging outcomes of single-row and double-row suture anchor fixation in arthroscopic rotator cuff repair with emphasis on analysis of the effect of various tear size on repair integrity. Methods Fifty-three patents were randomized to either single-row or double-row rotator cuff repair at the time of surgical intervention. The clinical results were evaluated by applying the UCLA score and the ASES index and assessing muscle strength in abduction and external rotation with a minimum 2-year follow-up. The postoperative rotator cuff integrity was evaluated by magnetic resonance arthrography at 6-month and minimum 2-year follow-up. Results We enrolled 27 patients in the single-row group and 26 patients in the double-row group. Statistically, the UCLA score; the ASES index; and muscle strength were significantly increased in both groups after surgery, but there was no significant difference between the 2 groups. At minimum 2-year follow-up, intact rotator cuffs were found in 17 patients in the single-row group and 20 in the double-row group, based on magnetic resonance arthrography results. Overall, there was no significant difference in postoperative structural integrity between the 2 groups at 6-month and 2-year follow-up. In patients with tear size larger than 3 cm, the muscle strength of the shoulder was significantly better in the double-row group. For the final imaging results, regardless of the tear size, there was no difference between the single-row and double-row groups. Conclusions Arthroscopic rotator cuff repair with double-row fixation showed better shoulder strength in patients with larger tear size (>3 cm) in comparison with single-row fixation. However, the imaging results showed no significant difference in cuff integrity in both groups in patients with any tear size at 6-month and minimum 2-year follow-up. Level of Evidence Level II, lesser-quality randomized control trial.