human
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: 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 ×  
    Output:
    
agent
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: 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 ×  
    Output:
    