Meta-Analysis and Evidence Base for the Efficacy of Autologous Bone Marrow Mesenchymal Stem Cells in Knee Cartilage Repair: Methodological Guidelines and Quality Assessment

Mohamed E Awad, Khaled A Hussein, Inas Helwa, Mohamed F Abdelsamid, Alexandra Aguilar-Perez, Ibrahim Mohsen, Monte Hunter, Mark W Hamrick, Carlos M Isales, Mohammed Elsalanty, William D Hill, Sadanand Fulzele, Mohamed E Awad, Khaled A Hussein, Inas Helwa, Mohamed F Abdelsamid, Alexandra Aguilar-Perez, Ibrahim Mohsen, Monte Hunter, Mark W Hamrick, Carlos M Isales, Mohammed Elsalanty, William D Hill, Sadanand Fulzele

Abstract

The aim of this study is to review all the published clinical trials on autologous bone marrow mesenchymal stem cells (BM-MSCs) in the repair of cartilage lesions of the knee. We performed a comprehensive search in three electronic databases: PubMed, Medline via Ovid, and Web of Science. A systematic review was conducted according to the guidelines of PRISMA protocol and the Cochrane Handbook for Systematic Reviews of Interventions. The modified Coleman methodology score was used to assess the quality of the included studies. Meta-analysis was conducted to estimate the effect size for Pain and function change after receiving BM-MSCs. Thirty-three studies-including 724 patients of mean age 44.2 years-were eligible. 50.7% of the included patients received cultured BM-MSCs for knee cartilage repair. There was improvement in the MINORS quality score over time with a positive correlation with the publication year. Meta-analysis indicated better improvement and statistical significance in the Visual Analog Scale for Pain, IKDC Function, Tegner Activity Scale, and Lysholm Knee Score after administration of noncultured BM-MSCs when compared to evaluation before the treatment. Meanwhile, there was a clear methodological defect in most studies with an average modified Coleman methodology score (MCMS) of 55. BM-MSCs revealed a clinically relevant improvement in pain, function, and histological regeneration.

Figures

Figure 1
Figure 1
Flow chart showing search strategy and study identification, inclusion, and exclusion.
Figure 2
Figure 2
Classification of the included study-based preparation of BM-MSCs and delivery method.
Figure 3
Figure 3
(a) Box plot showing the median, quartiles, and extreme values of the modified Coleman methodology score (CMS) for each level-of-evidence rating. (b) Box plot showing the median, quartiles, and extreme values of the modified Coleman methodology score (CMS) for each type of therapy. (c) Box plot showing the median, quartiles, and extreme values of the modified Coleman methodology score (CMS) for cell handling.
Figure 4
Figure 4
Modified Coleman methodology score (CMS) for studies reporting outcome after administration of BM-MSCs for cartilage repair plotted against publication year. There is a positive correlation (r = 0.16). The correlation was not statistically significant when unweighted (P = 0.3544).
Figure 5
Figure 5
(a) Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies. (b) Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Figure 6
Figure 6
(a) Forest plot comparing the Visual Analog Scale for Pain (VAS Pain) before and after administration of noncultured bone marrow aspirate concentrate (BMAC). (b) Forest plot comparing the International Knee Documentation Committee (IKDC) function level before and after administration of noncultured bone marrow aspirate concentrate (BMAC). (c) Forest plot comparing Tegner Activity Scale function level before and administration of noncultured bone marrow aspirate concentrate (BMAC). (d) Forest plot comparing the Lysholm Knee Score before and after administration of noncultured bone marrow aspirate concentrate (BMAC).
Figure 7
Figure 7
Guideline chart for the required data to be reported in future clinical trials.

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