Comparative outcomes of open-wedge high tibial osteotomy with platelet-rich plasma alone or in combination with mesenchymal stem cell treatment: a prospective study. Adipose Mesenchymal Stromal Cell-Based Therapy for Severe Osteoarthritis of the Knee: A Phase I Dose-Escalation Trial. Adipose Derived Stromal Cell (ADSC) Injections for Pain Management of Osteoarthritis in the Human Knee Joint. Culture-expanded allogenic adipose tissue-derived stem cells attenuate cartilage degeneration in an experimental rat osteoarthritis model Effect of adipose-derived mesenchymal stem and regenerative cells on lameness in dogs with chronic osteoarthritis of the coxofemoral joints: a randomized, double-blinded, multicenter, controlled trial. Adipose-Derived Mesenchymal Stem Cells With Microfracture Versus Microfracture Alone: 2-Year Follow-up of a Prospective Randomized Trial. Patient Profiling in Cartilage Regeneration: Prognostic Factors Determining Success of Treatment for Cartilage Defects
PURPOSE This study compared the clinical results and second-look arthroscopic findings of patients undergoing open-wedge high tibial osteotomy ( HTO ) for varus deformity , with or without mesenchymal stem cell ( MSC ) therapy .  METHODS This prospect i ve , comparative observational study was design ed to evaluate the effectiveness of MSC therapy . The patients were divided into 2 groups : HTO with platelet-rich plasma ( PRP ) injection only ( n = 23 ) or HTO in conjunction with MSC therapy and PRP injection ( n = 21 ) . Prospect i ve evaluations of both groups were performed using the Lysholm score , Knee Injury and Osteoarthritis Outcome Score ( KOOS ) , and a visual analog scale ( VAS ) score for pain . Second-look arthroscopy was carried out in all patients at the time of metal removal . RESULTS The patients in the MSC-PRP group showed significantly greater improvements in the KOOS subscales for pain ( PRP only , 74.0 ± 5.7 ; MSC-PRP , 81.2 ± 6.9 ; P < .001 ) and symptoms ( PRP only , 75.4 ± 8.5 ; MSC-PRP , 82.8 ± 7.2 ; P = .006 ) relative to the PRP-only group . Although the mean Lysholm score was similarly improved in both groups ( PRP only , 80.6 ± 13.5 ; MSC-PRP , 84.7 ± 16.2 ; P = .357 ) , the MSC-PRP group showed a significantly greater improvement in the VAS pain score  ( PRP only , 16.2 ± 4.6 ; MSC-PRP , 10.2 ± 5.7 ; P < .001 ) . There were no differences in the preoperative ( PRP only , varus 2.8 ° ± 1.7 ° ; MSC-PRP , varus 3.4 ° ± 3.0 ° ; P = .719 ) and postoperative ( PRP only , valgus 9.8 ° ± 2.4 ° ; MSC-PRP , valgus 8.7 ° ± 2.3 ° ; P = .678 ) femorotibial angles or weight-bearing lines between the groups . Arthroscopic evaluation , at plate removal , showed that partial or even fibrocartilage coverage was achieved in 50 % of the MSC-PRP group patients but in only 10 % of the patients in the PRP-only group ( P < .001 ) . CONCLUSIONS MSC therapy , in conjunction with HTO , mildly improved cartilage healing and showed good clinical results in some KOOS subscores and the VAS pain score compared with PRP only . LEVEL OF EVIDENCE Level II , prospect i ve comparative study UNLABELLED : Osteoarthritis ( OA ) is the most widespread musculoskeletal disorder in adults . It leads to cartilage damage associated with subchondral bone changes and synovial inflammation , causing pain and disability . The present study aim ed at evaluating the safety of a dose-escalation protocol of intra-articular injected adipose-derived stromal cells ( ASCs ) in patients with knee OA , as well as clinical efficacy as secondary endpoint . A bicentric , uncontrolled , open phase I clinical trial was conducted in France and Germany with regulatory agency approval for ASC expansion procedure in both countries . From April 2012 to December 2013 , 18 consecutive patients with symptomatic and severe knee OA were treated with a single intra-articular injection of autologous ASCs . The study design consisted of three consecutive cohorts ( six patients each ) with dose escalation : low dose ( 2 × 10(6 ) cells ) , medium dose ( 10 × 10(6 ) ) , and high dose ( 50 × 10(6 ) ) . The primary outcome parameter was safety evaluated by recording adverse events throughout the trial , and secondary parameters were pain and function subscales of the Western Ontario and McMaster Universities Arthritis Index . After 6 months of follow-up , the procedure was found to be safe , and no serious adverse events were reported . Four patients experienced transient knee joint pain and swelling after local injection . Interestingly , patients treated with low-dose ASCs experienced significant improvements in pain levels and function compared with baseline . Our data suggest that the intra-articular injection of ASCs is a safe therapeutic alternative to treat severe knee OA patients . A placebo-controlled double-blind phase IIb study is being initiated to assess clinical and structural efficacy . SIGNIFICANCE Although this phase I study included a limited number of patients without a placebo arm , it showed that local injection of autologous adipose-derived stem cells was safe and well tolerated in patients with knee osteoarthritis . This study also provides encouraging preliminary evidence of efficacy . Larger and controlled long-term studies are now m and atory to confirm whether this new strategy of cell therapy can improve pain and induce structural benefit in osteoarthritis BACKGROUND This safety and feasibility study used autologous adipose-derived stromal vascular cells ( the stromal vascular fraction [ SVF ] of adipose tissue ) , to treat 8 osteoarthritic knees in 6 patients of grade I to III ( K-L scale ) with initial pain of 4 or greater on a 10-point Visual Analog Scale ( VAS ) . OBJECTIVES The primary objective of the study was evaluation of the safety of intra-articular injection of SVF .  The secondary objective was to assess initial feasibility for reduction of pain in osteoarthritic knees . METHODS Adipose-derived SVF cells were obtained through enzymatic disaggregation of lipoaspirate , resuspension in 3 mL of Lactated Ringer 's Solution , and injection directly into the intra-articular space of the knee , with a mean of 14.1 million viable , nucleated SVF cells per knee . Metrics included monitoring of adverse events and preoperative to postoperative changes in the Western Ontario and McMaster Universities Arthritis Index ( WOMAC ) , the VAS pain scale , range of motion ( ROM ) , timed up- and -go ( TUG ) , and MRI . RESULTS No infections , acute pain flares , or other adverse events were reported . At 3-months postoperative , there was a statistically significant improvement in WOMAC and VAS scores ( P < .02 and P < .001 , respectively ) , which was maintained at 1 year . Physical therapy measurements for ROM and TUG both improved from preoperative to 3-months postoperative . St and ard MRI assessment from preoperative to 3-months postoperative showed no detectable structural differences . All patients attained full activity with decreased knee pain . CONCLUSIONS Autologous SVF was shown to be safe and to present a new potential therapy for reduction of pain for osteoarthritis of the knee . LEVEL OF EVIDENCE 4 : Therapeutic Mesenchymal stem cell (MSC)-based cell therapy is a promising avenue for osteoarthritis ( OA ) treatment . In the present study , we evaluated the efficacy of intra-articular injections of culture-exp and ed allogenic adipose tissue-derived stem cells ( ADSCs ) for the treatment of anterior cruciate ligament transection ( ACLT ) induced rat OA model . The paracrine effects of major histocompatibility complex (MHC)-unmatched ADSCs on chondrocytes were investigated in vitro . Rats were divided into an  OA group that underwent ACLT surgery  and a  sham-operated group that did not undergo ACLT surgery .  Four weeks after surgery mild OA was induced in the OA group . Subsequently , the OA rats were r and omly divided into ADSC and control groups . A single dose of 1 × 106 ADSCs suspended in 60 μL phosphate-buffered saline ( PBS ) was intra-articularly injected into the rats of the ADSC group . The control group received only 60 μL PBS . OA progression was evaluated macroscopically and histologically at 8 and 12 weeks after surgery . ADSC treatment did not cause any adverse local or systemic reactions . The degeneration of articular cartilage was significantly weaker in the ADSC group compared to that in the control group at both 8 and 12 weeks . Chondrocytes were co-cultured with MHC-unmatched ADSCs in trans-wells to assess the paracrine effects of ADSCs on chondrocytes . Co-culture with ADSCs counteracted the IL-1β-induced mRNA upregulation of the extracellular matrix-degrading enzymes MMP-3 and MMP-13 and the pro-inflammatory cytokines TNF-α and IL-6 in chondrocytes . Importantly , ADSCs increased the expression of the anti-inflammatory cytokine IL-10 in chondrocytes . The results of this study indicated that the intra-articular injection of culture-exp and ed allogenic ADSCs attenuated cartilage degeneration in an experimental rat OA model without inducing any adverse reactions . MHC-unmatched ADSCs protected chondrocytes from inflammatory factor-induced damage . The paracrine effects of ADSCs on OA chondrocytes are at least part of the mechanism by which ADSCs exert their therapeutic activity Autologous stem cell therapy in the field of regenerative veterinary medicine involves harvesting tissue , such as fat , from the patient , isolating the stem and regenerative cells , and administering the cells back to the patient . Autologous adipose-derived stem cell therapy has been commercially available since 2003 , and the current study evaluated such therapy in dogs with chronic osteoarthritis of the hip . Dogs treated with adipose-derived stem cell therapy had significantly improved scores for lameness and the compiled scores for lameness , pain , and range of motion compared with control dogs . This is the first r and omized , blinded , placebo-controlled clinical trial reporting on the effectiveness of stem cell therapy in dogs PURPOSE To compare the clinical and radiologic efficacy of adipose-derived stem cells ( ADSCs ) with fibrin glue and microfracture ( MFX ) versus MFX alone in patients with symptomatic knee cartilage defects . METHODS Patients who were aged 18 to 50 years and had a single International Cartilage Repair Society grade III/IV symptomatic cartilage defect ( ≥3 cm(2 ) ) on the femoral condyle were  r and omized  to receive ADSCs with fibrin glue and MFX treatment ( group 1 , n = 40 ) or MFX treatment alone ( group 2 , n = 40 ) . There was a lack of blinding for patients because of the additional intervention method ( liposuction ) . The cartilage defect was diagnosed using preoperative magnetic resonance imaging ( MRI ) , and quantitative and qualitative assessment s of the repair tissue were carried out at 24 months by using the Magnetic Resonance Observation of Cartilage Repair Tissue scoring system with follow-up MRI . Clinical results were evaluated using the Lysholm score , the Knee Injury and Osteoarthritis Outcome Score ( KOOS ) , and a 10-point visual analog scale for pain ( 0 points , no pain ; 10 points , worst possible pain ) preoperatively and postoperatively at 3 months , 12 months , and the last follow-up visit . RESULTS The 2 groups had similar baseline patient characteristics . Follow-up MRI was performed at 24 months ( mean , 24.3 months ; range , 24.0 to 25.1 months ) after the operation . Group 1 included 26 patients ( 65 % ) who had complete cartilage coverage of the lesion at follow-up compared with 18 patients ( 45 % ) in group 2 . Significantly better signal intensity was observed for the repair tissue in group 1 , with 32 patients ( 80 % ) having normal or nearly normal signal intensity ( i.e. , complete cartilage coverage of the lesion ) compared with 28 patients ( 72.5 % ) in group 2 . The mean clinical follow-up period was 27.4 months ( range , 26 to 30 months ) . The improvements in the mean KOOS pain and symptom subscores were significantly greater at follow-up in group 1 than in group 2 ( pain , 36.6 ± 11.9 in group 1 and 30.1 ± 14.7 in group 2 [ P = .034 ] ; symptoms , 32.3 ± 7.2 in group 1 and 27.8 ± 6.8 in group 2 [ P = .005 ] ) . However , the improvements in the other subscores were not significantly different between group 1 and group 2 ( activities of daily living , 38.5 ± 12.8 and 37.6 ± 12.9 , respectively [ P = .767 ] ; sports and recreation , 33.9 ± 10.3 and 31.6 ± 11.0 , respectively [ P = .338 ] ; quality of life , 38.4 ± 13.1 and 37.8 ± 12.0 , respectively [ P = .650 ] ) . Among the 80 patients ,  second-look arthroscopies  were performed in 57 knees ( 30 in group 1 and 27 in group 2 ) , and biopsy procedures were performed during these arthroscopies for 18 patients in group 1 and 16 patients in group 2 . The second-look arthroscopies showed good repair tissue quality , although no significant intergroup difference was observed . The mean total histologic score was 1,054 for group 1 compared with 967 for group 2 ( P = .036 ) . Age , lesion size , duration of symptoms before surgery , mechanism of injury , and combined procedures were not correlated with clinical results , Magnetic Resonance Observation of Cartilage Repair Tissue scores , and histologic outcomes at short-term follow-up . CONCLUSIONS Compared with MFX alone , MFX and ADSCs with fibrin glue provided radiologic and KOOS pain and symptom subscore improvements , with no differences in activity , sports , or quality -of-life subscores , in symptomatic single cartilage defects of the knee that were 3 cm(2 ) or larger , with similar structural repair tissue . LEVEL OF EVIDENCE Level II , prospect i ve comparative study Background Cartilage therapy for focal articular lesions has been implemented for more than a decade , and it is becoming increasingly available . What is still lacking , however , is analysis of patient characteristics to help improve outcome or select patients for specific treatment . Purpose To analyze the prognostic value of patient age and defect size , age , and location on clinical outcome 3 years after cartilage therapy . Study Design Cohort study ; Level of evidence , 3 . Methods Fifty-five patients ( age , 35 ± 9 years ) were r and omly selected from a prospect i ve data base . Each had a traumatic knee injury , each was treated for a focal cartilage lesion , and each was assessed with the Knee injury and Osteoarthritis Outcome Score ( KOOS ) 3 years after surgery . Patient characteristics ( ie , patient age and defect size , age , and location ) were tested for valid inclusion in the regression model . Multiple linear regression was used to determine which variables influenced clinical improvement . Binary KOOS scores were generated on the basis of age-matched healthy patients and assessed in a logistic regression analysis . Results Normality tests confirmed normal distribution for each variable ( P < .05 ) . Defect size did not influence clinical improvement ( P > .05 ) . Clinical outcome regarding the treatment of medial defects was better than that of the lateral defects ( 10.38 - 25.26 points for the different KOOS subscales ; P < .05 ) . The KOOS improvement from baseline was better for patients < 30 years compared with patients > 30 years ( 7.31 - 29.24 points for the different KOOS subscales ; P < .05 ) . Patients with defects < 24 months were more likely to report the age-matched healthy reference KOOS ( odds ratio , 1.8 - 4.0 ; P < .05 ) . Conclusion This study illustrates the influence of patient age and defect location and age on clinical outcome 3 years after treatment of a focal cartilage lesion in patients with a traumatic knee injury
Purpose The purpose of this systematic review is to evaluate the effects of adipose derived mesenchymal stem cells ( ADSCs ) in the treatment of osteoarthritis ( OA ) in the clinical setting .
While SVF may produce favorable clinical outcomes with minimal risk of side effects on osteoarthritis , the variability in the data and the use of biological adjuvants have confounded the effectiveness of ADSCs .