Treatment of Knee Osteoarthritis With Autologous Mesenchymal Stem Cells: A Pilot Study 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. Intra-articular injection of mesenchymal stem cells for the treatment of osteoarthritis of the knee: a proof-of-concept clinical trial. Osteocel Plus Cellular Allograft in Anterior Cervical Discectomy and Fusion: Evaluation of Clinical and Radiographic Outcomes From a Prospective Multicenter Study Treatment of Knee Osteoarthritis With Allogeneic Bone Marrow Mesenchymal Stem Cells: A Randomized Controlled Trial Adult human mesenchymal stem cells delivered via intra-articular injection to the knee following partial medial meniscectomy: a randomized, double-blind, controlled study. Mesenchymal stem cell therapy for knee osteoarthritis. Preliminary report of four patients Utilizing Autologous Multipotent Mesenchymal Stromal Cells and β-Tricalcium Phosphate Scaffold in Human Bone Defects: A Prospective, Controlled Feasibility Trial Intra-articular injection of two different doses of autologous bone marrow mesenchymal stem cells versus hyaluronic acid in the treatment of knee osteoarthritis: multicenter randomized controlled clinical trial (phase I/II) Intervertebral Disc Repair by Autologous Mesenchymal Bone Marrow Cells: A Pilot Study An exploratory clinical trial for idiopathic osteonecrosis of femoral head by cultured autologous multipotent mesenchymal stromal cells augmented with vascularized bone grafts. Matrix-induced autologous mesenchymal stem cell implantation versus matrix-induced autologous chondrocyte implantation in the treatment of chondral defects of the knee: a 2-year randomized study Treatment of early stage osteonecrosis of the femoral head with autologous implantation of bone marrow-derived and cultured mesenchymal stem cells. Adipose-Derived Mesenchymal Stem Cells With Microfracture Versus Microfracture Alone: 2-Year Follow-up of a Prospective Randomized Trial. Mesenchymal stem cell therapy for knee osteoarthritis: 5 years follow‐up of three patients Injectable cultured bone marrow-derived mesenchymal stem cells in varus knees with cartilage defects undergoing high tibial osteotomy: a prospective, randomized controlled clinical trial with 2 years' follow-up.
Background Osteoarthritis is the most prevalent joint disease and a frequent cause of joint pain , functional loss , and disability . Osteoarthritis often becomes chronic , and conventional treatments have demonstrated only modest clinical benefits without lesion reversal . Cell-based therapies have shown encouraging results in both animal studies and a few human case reports . We design ed a pilot study to assess the feasibility and safety of osteoarthritis treatment with mesenchymal stromal cells ( MSCs ) in humans and to obtain early efficacy information for this treatment . Methods Twelve patients with chronic knee pain unresponsive to conservative treatments and radiologic evidence of osteoarthritis were treated with autologous exp and ed bone marrow MSCs by intra-articular injection ( 40 × 106 cells ) . Clinical outcomes were followed for 1 year and included evaluations of pain , disability , and quality of life . Articular cartilage quality was assessed by quantitative magnetic resonance imaging T2 mapping . Results Feasibility and safety were confirmed , and strong indications of clinical efficacy were identified . Patients exhibited rapid and progressive improvement of algofunctional indices that approached 65 % to 78 % by 1 year . This outcome compares favorably with the results of conventional treatments . Additionally , quantification of cartilage quality by T2 relaxation measurements demonstrated a highly significant decrease of poor cartilage areas ( on average , 27 % ) , with improvement of cartilage quality in 11 of the 12 patients . Conclusions MSC therapy may be a valid alternative treatment for  chronic knee osteoarthritis . The intervention is simple , does not require hospitalization or surgery , provides pain relief , and significantly improves cartilage quality 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 Mesenchymal stem cells ( MSCs ) are known to have a potential for articular cartilage regeneration . However , most studies focused on focal cartilage defect through surgical implantation . For the treatment of generalized cartilage loss in osteoarthritis , an alternative delivery strategy would be more appropriate . The purpose of this study was to assess the safety and efficacy of intra-articular injection of autologous adipose tissue derived MSCs ( AD-MSCs ) for knee osteoarthritis  . We enrolled 18 patients with osteoarthritis of the knee and injected AD MSCs into the knee . The phase I study consists of three dose-escalation cohorts ; the low-dose ( 1.0 × 10(7 ) cells ) , mid-dose ( 5.0 × 10(7 ) ) , and high-dose ( 1.0 × 10(8 ) ) group with three patients each . The phase II included nine patients receiving the high-dose . The primary outcomes were the safety and the Western Ontario and McMaster Universities Osteoarthritis index ( WOMAC ) at 6 months . Secondary outcomes included clinical , radiological , arthroscopic , and histological evaluations . There was no treatment-related adverse event . The WOMAC score improved at 6 months after injection in the high-dose group . The size of cartilage defect decreased while the volume of cartilage increased in the medial femoral and tibial condyles of the high-dose group . Arthroscopy showed that the size of cartilage defect decreased in the medial femoral and medial tibial condyles of the high-dose group . Histology demonstrated thick , hyaline-like cartilage regeneration . These results showed that intra-articular injection of 1.0 × 10(8 ) AD MSCs into the osteoarthritic knee improved function and pain of the knee joint without causing adverse events , and reduced cartilage defects by regeneration of hyaline-like articular cartilage Study Design . Prospect i ve , multicenter , nonr and omized , institutional review board-approved clinical and radiographic study . Objective . To evaluate and summarize the 2-year outcomes of patients treated with Osteocel Plus cellular allograft as part of an anterior cervical discectomy and fusion procedure . Summary of Background Data . Osteocel Plus is an allograft cellular bone matrix containing native mesenchymal stem cells and osteoprogenitor cells that is intended to mimic the performance of iliac crest autograft without the morbidity associated with its harvest . Methods . A total of 182 patients were treated with anterior cervical discectomy and fusion using Osteocel Plus in a polyetheretherketone cage and anterior plating at 1 or 2 consecutive levels . Clinical outcomes included visual analogue scale for neck and arm pain , neck disability index , and SF-12 physical and mental component scores . Computed tomography and plain film radiographic measures included assessment of bridging bone , disc height , disc angle , and segmental range of motion . Results . A total of 249 levels were treated in 182 patients .  Mean procedure time was 100 minutes , blood loss was less than 50 mL in 93 % of patients , and hospital stay was 1 day or less in 84 % of patients . Significant ( P < 0.05 ) average improvements in clinical outcomes from preoperatively to 24 months included the following : neck disability index : 21.5 % ; visual analogue scale neck : 34 mm ; visual analogue scale arm : 35 mm ; SF-12 physical component score : 11.2 ; SF-12 mental component score : 6.8 . At 24 months , 93 % of patients were satisfied with their outcome . In patients treated at a single level with a minimum of 24-month follow-up , 92 % ( 79/86 ) of levels achieved solid bridging and 95 % of levels demonstrated range of motion of less than 3 ° . In combined single- and 2-level procedures , 87 % ( 157/180 ) of levels achieved solid bridging and 92 % ( 148/161 ) had range of motion of less than 3 ° at 24 months . No patient required revision for pseudarthrosis . Conclusion . Improvements in clinical results at 2 years , high patient satisfaction , and high radiographic and clinical fusion rates provide confidence in Osteocel Plus as an effective alternative to structural allograft or autograft in anterior cervical discectomy and fusion procedures . Level of Evidence : Background Osteoarthritis is the most prevalent joint disease and a common cause of joint pain , functional loss , and disability . Conventional treatments demonstrate only modest clinical benefits without lesion reversal . Autologous mesenchymal stromal cell ( MSC ) treatments have shown feasibility , safety , and strong indications for clinical efficacy . We performed a r and omized , active control trial to assess the feasibility and safety of treating osteoarthritis with allogeneic MSCs , and we obtain information regarding the efficacy of this treatment . Methods We r and omized 30 patients with chronic knee pain unresponsive to conservative treatments and showing radiological evidence of osteoarthritis into 2 groups of 15 patients . The test group was treated with allogeneic bone marrow MSCs by intra-articular injection of 40 × 106 cells . The control group received intra-articular hyaluronic acid ( 60 mg , single dose ) . Clinical outcomes were followed for 1 year and included evaluations of pain , disability , and quality of life . Articular cartilage quality was assessed by quantitative magnetic resonance imaging T2 mapping . Results Feasibility and safety were confirmed and indications of clinical efficacy were identified . The MSC-treated patients displayed significant improvement in algofunctional indices versus the active controls treated with hyaluronic acid . Quantification of cartilage quality by T2 relaxation measurements showed a significant decrease in poor cartilage areas , with cartilage quality improvements in MSC-treated patients . Conclusions Allogeneic MSC therapy may be a valid alternative for the treatment of  chronic knee osteoarthritis  that is more logistically convenient than autologous MSC treatment . The intervention is simple , does not require surgery , provides pain relief , and significantly improves cartilage quality BACKGROUND There are limited treatment options for tissue restoration and the prevention of  degenerative changes in the knee .  Stem cells have been a focus of intense pre clinical research into tissue regeneration but limited clinical investigation . In a r and omized , double-blind , controlled study , the safety of the intra-articular injection of human mesenchymal stem cells into the knee , the ability of mesenchymal stem cells to promote meniscus regeneration following partial meniscectomy , and the effects of mesenchymal stem cells on osteoarthritic changes in the knee were investigated . METHODS A total of fifty-five patients at seven institutions underwent a partial medial meniscectomy .  A single superolateral knee injection was given within seven to ten days after the meniscectomy . Patients were r and omized to one of three treatment groups : Group A , in which patients received an injection of 50 × 10⁶ allogeneic mesenchymal stem cells ; Group B , 150 × 10⁶ allogeneic mesenchymal stem cells ; and the control group , a sodium hyaluronate ( hyaluronic acid/hyaluronan ) vehicle control . Patients were followed to evaluate safety , meniscus regeneration , the overall condition of the knee joint , and clinical outcomes at intervals through two years . Evaluations included sequential magnetic resonance imaging ( MRI ) . RESULTS No ectopic tissue formation or clinical ly important safety issues were identified . There was significantly increased meniscal volume ( defined a priori as a 15 % threshold ) determined by quantitative MRI in 24 % of patients in Group A and 6 % in Group B at twelve months post meniscectomy ( p = 0.022 ) . No patients in the control group met the 15 % threshold for increased meniscal volume . Patients with osteoarthritic changes who received mesenchymal stem cells experienced a significant reduction in pain compared with those who received the control , on the basis of visual analog scale assessment s. CONCLUSIONS There was evidence of meniscus regeneration and improvement in knee pain following treatment with allogeneic human mesenchymal stem cells . These results support the study of human mesenchymal stem cells for the apparent knee-tissue regeneration and protective effects Background : Osteoarthritis ( OA ) is a cartilage degenerative process , involving the immune system , producing local inflammatory reactions , with production of pro‐inflammatory cytokines and metalloproteinases . No treatment is still available to improve or reverse the process . Stem cell therapy opened new horizons for treatment of many incurable diseases . Mesenchymal stem cells ( MSCs ) due to their multi‐lineage potential , immunosuppressive activities , limited immunogenicity and relative ease of growth in culture , have attracted attentions for clinical use The purpose of this prospect i ve controlled study was to compare healing quality following the implantation of ultraporous β-tricalcium phosphate , containing either exp and ed autologous mesenchymal stromal cells  ( trial group , 9 patients )  or β-tricalcium phosphate alone  ( control group , 9 patients ) , into femoral defects during revision total hip arthroplasty . Both groups were assessed using the Harris Hip Score , radiography , and DEXA scanning at 6 weeks and 3 , 6 , and 12 months postoperatively . A significant difference in the bone defect healing was observed between both groups of patients ( P < 0.05 ) . In the trial group , trabecular remodeling was found in all nine patients and in the control group , in 1 patient only . Whereas , over the 12-month follow-up period , no significant difference was observed between both groups of patients in terms of the resorption of β-tricalcium phosphate , the significant differences were documented in the presence of radiolucency and bone trabeculation through the defect ( P < 0.05 ) . Using autologous mesenchymal stromal cells combined with a β-tricalcium phosphate scaffold is a feasible , safe , and effective approach for management of bone defects with compromised microenvironment . The clinical trial was registered at the EU Clinical Trials Register before patient recruitment has begun ( EudraCT number 2012 - 005599 - 33 ) Abstract Background Mesenchymal stromal cells are a promising option to treat  knee osteoarthritis . Their safety and usefulness must be confirmed and the optimal dose established . We tested increasing doses of bone marrow mesenchymal stromal cells ( BM-MSCs ) in combination with hyaluronic acid in a r and omized clinical trial . Material sA phase I/II multicenter r and omized clinical trial with active control was conducted . Thirty patients diagnosed with knee OA were r and omly assigned to intraarticularly administered hyaluronic acid alone ( control ) , or together with 10 × 106 or 100 × 106 cultured autologous BM-MSCs , and followed up for 12 months . Pain and function were assessed using VAS and WOMAC and by measuring the knee motion range . X-ray and magnetic resonance imaging analyses were performed to analyze joint damage . Results No adverse effects were reported after BM-MSC administration or during follow-up . BM-MSC-administered patients improved according to VAS during all follow-up evaluations and median value ( IQR ) for control , low-dose and high-dose groups change from 5 ( 3 , 7 ) , 7 ( 5 , 8) and 6 ( 4 , 8) to 4 ( 3 , 5 ) , 2 ( 1 , 3 ) and 2 ( 0,4 ) respectively at 12 months ( low-dose vs control group p = 0.005 and high-dose vs control group p < 0.009 ) . BM-MSC-administered patients were also superior according to WOMAC , although improvement in control and low-dose patients could not be significantly sustained beyond 6 months . On the other h and , the BM-MSC high-dose group exhibited an improvement of 16.5 ( 12 , 19 ) points at 12 months ( p < 0.01 ) . Consistent with WOMAC and VAS values , motion ranges remained unaltered in the control group but improved at 12 months with BM-MSCs . X-ray revealed a reduction of the knee joint space width in the control group that was not seen in BM-MSCs high-dose group . MRI ( WORMS protocol ) showed that joint damage decreased only in the BM-MSC high-dose group , albeit slightly . Conclusions The single intraarticular injection of in vitro exp and ed autologous BM-MSCs together with HA is a safe and feasible procedure that results in a clinical and functional improvement of knee OA , especially when 100 × 106 cells are administered . These results pave the way for a future phase III clinical trial . Clinical Trials.gov identifier NCT02123368 . Nº EudraCT : 2009 - 017624 - Background . Degenerative disc disease may cause severe low-back pain , a large public health problem with significant economic and life quality impact . Chronic cases often require surgery , which may lead to biomechanical problems and accelerated degeneration of the adjacent segments . Cell-based therapies may circumvent these problems and have exhibited encouraging results in vitro and in animal studies . We design ed a pilot study to assess feasibility and safety and to obtain early indications on efficacy of treatment with mesenchymal stem cells ( MSC ) in humans . Methods . Ten patients with chronic back pain diagnosed with lumbar disc degeneration with intact annulus fibrosus were treated with autologous exp and ed bone marrow MSC injected into the nucleus pulposus area . Clinical evolution was followed for 1 year and included evaluation of back pain , disability , and quality of life . Magnetic resonance imaging measurements of disc height and fluid content were also performed . Results . Feasibility and safety were confirmed and strong indications of clinical efficacy identified . Patients exhibited rapid improvement of pain and disability ( 85 % of maximum in 3 months ) that approached 71 % of optimal efficacy . This outcome compares favorably with the results of other procedures such as spinal fusion or total disc replacement . Although disc height was not recovered , water content was significantly elevated at 12 months . Conclusions . MSC therapy may be a valid alternative treatment for  chronic back pain caused by degenerative disc disease . Advantages over current gold st and ards include simpler and more conservative intervention without surgery , preservation of normal biomechanics , and same or better pain relief Idiopathic osteonecrosis of femoral head ( ION ) is a painful disorder that progresses to collapse of the femoral head and destruction of the hip joint . Although its precise pathology remains unknown , the loss of blood supply causing the loss of living bone-forming cells is a hallmark of the pathophysiology of osteonecrosis . Transplantation of multipotent mesenchymal stromal cells ( MSCs ) is a promising tool for regenerating the musculoskeletal system . The aim of the present study was to assess the safety and efficacy of transplantation of cultured autologous bone marrow-derived MSCs mixed with β-tricalcium phosphate ( β-TCP ) in combination with vascularized bone grafts for the treatment of advanced stage ION in a clinical trial . Ten patients with stage 3 ION were enrolled in this study .  Autologous bone marrow-derived MSCs were cultured with autologous serum , and cells ( 0.5 - 1.0 × 10(8 ) ) were transplanted after mixing with β-TCP granules in combination with vascularized iliac bone grafts . Patients were assessed 24 months after treatment . The primary and secondary endpoints were progression of the radiological stage and changes in bone volume at the femoral head , and clinical score , respectively . Nine of ten patients completed the protocol , seven of whom remained at stage 3 , and the remaining two cases progressed to stage 4 . The average bone volume increased from 56.5±8.5 cm(3 ) to 57.7±10.6 cm(3 ) . The average clinical score according to the Japan Orthopaedic Association improved from 65.6±25.5 points to 87.9±19.0 points . One severe adverse event was observed , which was not related to the clinical trial . Although the efficacy of cell transplantation was still to be determined , all procedures were successfully performed and some young patients with extensive necrotic lesions with pain demonstrated good bone regeneration with amelioration of symptoms . Further improvements in our method using MSCs and the proper selection of patients will open a new approach for the treatment of this refractory disease Abstract Background Cell-based strategies that combine in vitro- exp and ed autologous chondrocytes with matrix scaffolds are currently preferred for full-thickness cartilage lesions of the knee ≥2 cm2 . Although this approach is reasonable , continuing advances in the field of cartilage repair will further exp and the options available to improve outcomes .Hypothesis/ purpose In the present clinical study , we compared the outcomes of matrix-induced autologous mesenchymal stem cell implantation ( m-AMI ) with matrix-induced autologous chondrocyte implantation ( m-ACI ) for the treatment of isolated chondral defects of the knee . Study design Prospect i ve , single-site , r and omized , single-blind pilot study . Methods Fourteen patients with isolated full-thickness chondral lesions of the knee > 2 cm2 were r and omized into two treatment groups : m-AMI and m-ACI . Outcomes were assessed pre-operatively and 3 , 6 , 12 and 24 months post-operatively . Results Clinical evaluations revealed that improvement from pre-operation to 24 months post-operation occurred in both groups ( p < 0.05 ) . At all follow-up intervals , m-AMI demonstrated significantly better functional outcomes ( motion deficit and straight leg raise strength ) than did m-ACI ( p < 0.05 ) . At all follow-up intervals , m-AMI demonstrated significantly better subjective sub-scale scores for pain , symptoms , activities of daily living and sport and recreation of the knee injury and osteoarthritis outcome score ( KOOS ) than did m-ACI ( p < 0.05 ) . Additionally , m-AMI demonstrated significantly better ( p < 0.05 ) scores than m-ACI for the quality of life sub-scale of the KOOS and visual analog scale ( VAS ) severity at the 6-month follow-up . The Tegner activity score and VAS frequency were not significantly different between the two groups . Graft failure was not observed on magnetic resonance imaging at the 24-month follow-up . m-AMI and m-ACI demonstrated very good-to-excellent and good-to-very good infill , respectively , with no adverse effects from the implant , regardless of the treatment . Conclusion For the treatment of isolated full-thickness chondral lesion of the knee , m-AMI can be used effectively and may potentially accelerate recovery . A larger patient cohort and follow-up supported by histological analyses are necessary to determine long-term outcomes BACKGROUND Treatment of early-stage osteonecrosis of the femoral head ( ONFH ) with autologous implantation of iliac crest bone marrow-derived mononuclear cells , which contain tens of thous and s of bone marrow mesenchymal stem cells ( BMMSCs ) , recently achieved a promising outcome . METHODS One hundred patients with early-stage ONFH were recruited and r and omly assigned to BMMSC treatment or core decompression ( CD ) treatment . Each BMMSC-treated hip received femoral head ( FH ) implantation of 2 × 10(6 ) autologous subtrochanteric bone marrow-derived and ex vivo exp and ed BMMSCs . The radiographic stage of ONFH according to the Association Research Circulation Osseous classification , Harris hip score ( HHS ) , and the volume of the necrotic lesion or the low signal intensity zone ( LowSIZ ) in the FH were assessed before and 6 , 12 , 24 , and 60 months after the initial operation . RESULTS Sixty months after the operation , only 2 of the 53 BMMSC-treated hips progressed and underwent vascularized bone grafting . In CD group , 7 hips lost follow-up , and 10 of the rest 44 hips progressed and underwent  vascularized bone grafting  ( 5 hips ) or total hip replacement ( 5 hips ) . Compared with the CD group , BMMSC treatment significantly improved the HHS as well as decreased the volume of femoral head LowSIZ of the hips preoperatively classified at stage IC , IIB , and IIC ( P<0.05 , respectively ; stage IIA , P=0.06 , respectively ) . No complication was observed in both treatment groups . CONCLUSIONS Ex vivo expansion of autologous BMMSCs can reliably provide a greater number of BMMSCs for FH implantation . This intervention is safe and effective in delaying or avoiding FH collapse , which may necessitate total hip replacement 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 Osteoarthritis is a degenerative joint disease characterized by the destruction of joint cartilage . Mesenchymal stem cells ( MSCs ) are found in low numbers in normal cartilage , mainly in the superficial layer , acting as repairing agents . In OA , MSCs are seen in larger numbers , but act chaotic and are unable to repair the cartilage . The synovial membrane becomes inflamed and interacts with the cartilage . Transplanted MSC have the ability to normalize them , redirecting them to their normal function . In a preliminary study , we showed that MSC could improve knee OA in four patients at 6 months . This report shows their long‐term follow‐up at 5 years PURPOSE To analyze the results of the use of intra-articular cultured autologous bone marrow-derived mesenchymal stem cell ( MSC ) injections in conjunction with microfracture and medial opening-wedge high tibial osteotomy ( HTO ) . METHODS Fifty-six knees in 56 patients with unicompartmental osteoarthritic knees and genu varum were r and omly allocated to the cell-recipient group ( n = 28 ) or control group ( n = 28 ) . Patients who had a joint line congruity angle of more than 2 ° , malalignment of the knee from femoral causes , a fixed flexion deformity , or age older than 55 years were excluded . All patients underwent HTO and microfracture .  The cell-recipient group received intra-articular injection of cultured MSCs with hyaluronic acid 3 weeks after surgery , whereas the control group only received hyaluronic acid . The primary outcome measure was the International Knee Documentation Committee ( IKDC ) score at intervals of 6 months , 1 year , and 2 years postoperatively . Secondary outcome measures were Tegner and Lysholm clinical scores and 1-year postoperative Magnetic Resonance Observation of Cartilage Repair Tissue ( MOCART ) scores . RESULTS The median age of the patients was 51 years , with a mean body mass index of 23.85 . Both treatment arms achieved improvements in Tegner , Lysholm , and IKDC scores . After adjustment for age , baseline scores , and time of evaluation , the cell-recipient group showed significantly better scores . The effect of treatment showed an added improvement of 7.65 ( 95 % confidence interval [ CI ] , 3.04 to 12.26 ; P = .001 ) for IKDC scores , 7.61 ( 95 % CI , 1.44 to 13.79 ; P = .016 ) for Lysholm scores , and 0.64 ( 95 % CI , 0.10 to 1.19 ; P = .021 ) for Tegner scores . Magnetic resonance imaging scans performed 1 year after surgical intervention showed significantly better MOCART scores for the cell-recipient group . The age-adjusted mean difference in MOCART score was 19.6 ( 95 % CI , 10.5 to 28.6 ; P < .001 ) . CONCLUSIONS Intra-articular injection of cultured MSCs is effective in improving both short-term clinical and MOCART outcomes in patients undergoing HTO and microfracture for varus knees with cartilage defects . LEVEL OF EVIDENCE Level II , r and omized controlled trial
Background : Mesenchymal stem cells ( MSCs ) are increasingly being used in the treatment of a wide variety of sports-related conditions .
Despite this enthusiasm , the biological properties of MSCs and their effects on musculoskeletal tissue healing remain poorly understood .
MSC-based strategies encompass cell population s with heterogeneous phenotypes isolated from multiple tissues and using different methods .
Therefore , comprehensive reporting of the source , preparation methods , and characteristics of MSC strategies is essential to enable interpretation of results .
Purpose : To perform a systematic review of levels of reporting of key variables in MSC preparation and composition for clinical studies evaluating MSC-based therapies in the treatment of musculoskeletal conditions .