Methodological Flaws in Meta-Analyses of Clinical Studies on the Management of Knee Osteoarthritis with Stem Cells: A Systematic Review

Abstract

(1) Background: Conclusions of meta-analyses of clinical studies may substantially influence opinions of prospective patients and stakeholders in healthcare. Nineteen meta-analyses of clinical studies on the management of primary knee osteoarthritis (pkOA) with stem cells, published between January 2020 and July 2021, came to inconsistent conclusions regarding the efficacy of this treatment modality. It is possible that a separate meta-analysis based on an independent, systematic assessment of clinical studies on the management of pkOA with stem cells may reach a different conclusion. (2) Methods: PubMed, Web of Science, and the Cochrane Library were systematically searched for clinical studies and meta-analyses of clinical studies on the management of pkOA with stem cells. All clinical studies and meta-analyses identified were evaluated in detail, as were all sub-analyses included in the meta-analyses. (3) Results: The inconsistent conclusions regarding the efficacy of treating pkOA with stem cells in the 19 assessed meta-analyses were most probably based on substantial differences in literature search strategies among different authors, misconceptions about meta-analyses themselves, and misconceptions about the comparability of different types of stem cells with regard to their safety and regenerative potential. An independent, systematic review of the literature yielded a total of 183 studies, of which 33 were randomized clinical trials, including a total of 6860 patients with pkOA. However, it was not possible to perform a scientifically sound meta-analysis. (4) Conclusions: Clinicians should interpret the results of the 19 assessed meta-analyses of clinical studies on the management of pkOA with stem cells with caution and should be cautious of the conclusions drawn therein. Clinicians and researchers should strive to participate in FDA and/or EMA reviewed and approved clinical trials to provide clinically and statistically valid efficacy.

Keywords: meta-analyses; primary knee osteoarthritis; stem cells; systematic review.

Figure 1

Systematic review flow chart of the first literature search regarding meta-analyses of clinical studies on the treatment of primary knee osteoarthritis with stem cells that were published between January 2020 and July 2021, performed according to the PRISMA guidelines [198] on 7 August 2021.

Figure 2

Systematic review flow chart of the second literature search regarding treatment of primary knee osteoarthritis with stem cells, performed according to the PRISMA guidelines [198] on 7 August 2021. Abbreviations: BMAC, bone marrow concentrate; ADRCs, adipose-derived regenerative cells; BM-MSCs, bone-marrow-derived mesenchymal stem cells; ADSCs, adipose-derived stem cells; MFF, micro-fragmented fat (from liposuction); and pBSCs, activated peripheral blood stem cells.