Expanded Mesenchymal Stromal Cells in knee osteoarthritis: A systematic literature review

Abstract

Objective: To analyse the efficacy and safety of intra-articular injection of expanded Mesenchymal Stromal Cells (MSCs) in knee osteoarthritis.

Methods: Systematic Literature Review. A pre-defined search strategy was run in Medline, Embase and Cochrane Library until February 2018.

Inclusion criteria: knee osteoarthritis (grades II-IV Kellgren-Lawrence); intra-articular injection of MSCs (without surgical co-treatments); Randomized Controlled Trials (RCTs) or Quasi-experimental Clinical Trials (QCTs) N ≥ 10 and ≥6 months of follow-up were included. Evidence was assigned according to the Scottish Intercollegiate Guidelines Network (SIGN).

Results: The search identified 252 articles. Nine proof-of-concept trials (3 RCTs, 6 QCTs) were included (N = 169). Evidence showed clinical improvement in 60% of patients. Structural benefit was reported in half of patients. Clinical benefit was observed from the 3^rd month and structural improvement from the 6^th. All studies reported maximum clinical and structural benefit a year following the implant. This benefit was sustained for up to 24 months. Studies with doses ≥40 × 10⁶ showed more consistent clinical and structural benefits than those with lower doses. No systemic adverse reactions were reported. The most common adverse effect was pain and/or inflammation in the puncture area (13-53%). The use of donor cells was as safe as autologous implants.

Conclusions: Intra-articular implants of MSCs seem to be safe with no serious adverse effects. Low-quality evidence precludes conclusions regarding efficacy in this review. However, the clinical and structural benefits observed provide a rationale for using expanded MSCs implants in osteoarthritis patients. High-quality evidence trials are needed to further determine best protocols to maximize clinical and structural improvement.

Keywords: Artrosis de rodilla; Células madre; Células mesenquimales estromales; Intra-articular treatment; Knee osteoarthritis; Mesenchymal Stromal Cells; Revisión sistemática; Systematic literature review; Tratamiento intra-articular.