Mesenchymal stem cells injections for knee osteoarthritis: a systematic overview

Background Thousands of systematic reviews have been conducted in all areas of health care. However, the methodological quality of these reviews is variable and should routinely be appraised. AMSTAR is a measurement tool to assess systematic reviews. Methodology AMSTAR was used to appraise 42 reviews focusing on therapies to treat gastro-esophageal reflux disease, peptic ulcer disease, and other acid-related diseases. Two assessors applied the AMSTAR to each review. Two other assessors, plus a clinician and/or methodologist applied a global assessment to each review independently. Conclusions The sample of 42 reviews covered a wide range of methodological quality. The overall scores on AMSTAR ranged from 0 to 10 (out of a maximum of 11) with a mean of 4.6 (95% CI: 3.7 to 5.6) and median 4.0 (range 2.0 to 6.0). The inter-observer agreement of the individual items ranged from moderate to almost perfect agreement. Nine items scored a kappa of >0.75 (95% CI: 0.55 to 0.96). The reliability of the total AMSTAR score was excellent: kappa 0.84 (95% CI: 0.67 to 1.00) and Pearson's R 0.96 (95% CI: 0.92 to 0.98). The overall scores for the global assessment ranged from 2 to 7 (out of a maximum score of 7) with a mean of 4.43 (95% CI: 3.6 to 5.3) and median 4.0 (range 2.25 to 5.75). The agreement was lower with a kappa of 0.63 (95% CI: 0.40 to 0.88). Construct validity was shown by AMSTAR convergence with the results of the global assessment: Pearson's R 0.72 (95% CI: 0.53 to 0.84). For the AMSTAR total score, the limits of agreement were −0.19±1.38. This translates to a minimum detectable difference between reviews of 0.64 ‘AMSTAR points’. Further validation of AMSTAR is needed to assess its validity, reliability and perceived utility by appraisers and end users of reviews across a broader range of systematic reviews.

First-generation autologous chondrocyte implantation has limitations, and introducing new effective cell sources can improve cartilage repair. This study was conducted to compare the clinical outcomes of patients treated with first-generation autologous chondrocyte implantation to patients treated with autologous bone marrow-derived mesenchymal stem cells (BMSCs). Cohort study; Level of evidence, 3. Seventy-two matched (lesion site and age) patients underwent cartilage repair using chondrocytes (n = 36) or BMSCs (n = 36). Clinical outcomes were measured before operation and 3, 6, 9, 12, 18, and 24 months after operation using the International Cartilage Repair Society (ICRS) Cartilage Injury Evaluation Package, which included questions from the Short-Form Health Survey, International Knee Documentation Committee (IKDC) subjective knee evaluation form, Lysholm knee scale, and Tegner activity level scale. There was significant improvement in the patients' quality of life (physical and mental components of the Short Form-36 questionnaire included in the ICRS package) after cartilage repair in both groups (autologous chondrocyte implantation and BMSCs). However, there was no difference between the BMSC and the autologous chondrocyte implantation group in terms of clinical outcomes except for Physical Role Functioning, with a greater improvement over time in the BMSC group (P = .044 for interaction effect). The IKDC subjective knee evaluation (P = .861), Lysholm (P = .627), and Tegner (P = .200) scores did not show any significant difference between groups over time. However, in general, men showed significantly better improvements than women. Patients younger than 45 years of age scored significantly better than patients older than 45 years in the autologous chondrocyte implantation group, but age did not make a difference in outcomes in the BMSC group. Using BMSCs in cartilage repair is as effective as chondrocytes for articular cartilage repair. In addition, it required 1 less knee surgery, reduced costs, and minimized donor-site morbidity.

Mesenchymal stem cells (MSCs) are multipotent cells capable of differentiation into mesenchymal lineages and that can be isolated from various tissues and easily cultivated in vitro. Currently, MSCs are of considerable interest because of the biological characteristics that confer high potential applicability in the clinical treatment of many diseases. Specifically, because of their high immunoregulatory capacity, MSCs are used as tools in cellular therapies for clinical protocols involving immune system alterations. In this review, we discuss the current knowledge about the capacity of MSCs for the immunoregulation of immunocompetent cells and emphasize the effects of MSCs on T cells, principal effectors of the immune response, and the immunosuppressive effects mediated by the secretion of soluble factors and membrane molecules. We also describe the mechanisms of MSC immunoregulatory modulation and the participation of MSCs as immune response regulators in several autoimmune diseases, and we emphasize the clinical application in graft versus host disease (GVHD).