Intraarticular injection of bone marrow-derived mesenchymal stem cells enhances regeneration in knee osteoarthritis

Abstract

Purpose: This review aimed to evaluate the efficacy of intra-articular injections of bone marrow derived mesenchymal stem cells (BM-MSCs) for the treatment of knee osteoarthritis (KOA).

Methods: This narrative review evaluates recent English language clinical data and published research articles between 2014 and 2019. Key word search strings of ((("bone marrow-derived mesenchymal stem cell" OR "bone marrow mesenchymal stromal cell" OR "bone marrow stromal cell")) AND ("osteoarthritis" OR "knee osteoarthritis")) AND ("human" OR "clinical"))) AND "intra-articular injection" were used to identify relevant articles using PMC, Cochrane Library, Web Of Science and Scopus databases.

Results: Pre-clinical studies have demonstrated successful, safe and encouraging results for articular cartilage repair and regeneration. This is concluded to be due to the multilineage differential potential, immunosuppressive and self-renewal capabilities of BM-MSCs, which have shown to augment pain and improve functional outcomes. Subsequently, clinical applications of intra-articular injections of BM-MSCs are steadily increasing, with most studies demonstrating a decrease in poor cartilage index, improvements in pain, function and Quality of Life (QoL); with moderate-to-high level evidence regarding safety for therapeutic administration. However, low confidence in clinical efficacy remains due to a plethora of heterogenous methodologies utilised, resulting in challenging study comparisons. A moderate number of cells (40 × 10⁶) were identified as most likely to achieve optimal responses in individuals with grade ≥ 2 KOA. Likewise, significant improvements were reported when using lower (24 × 10⁶) and higher (100 × 10⁶) cell numbers, although adverse effects including persistent pain and swelling were a consequence.

Conclusion: Overall, the benefits of intra-articular injections of BM-MSCs were deemed to outweigh the adverse effects; thus, this treatment be considered as a future therapy strategy. To realise this, long-term large-scale randomised clinical trials are required to enable improved interpretations, to determine the validity of efficacy in future studies.

Level of evidence: IV.

Keywords: Allogenic; Autologous; Cell therapies; Clinical efficacy; Immunomodulation; Mesenchymal stem cells; Optimal dosage; Osteoarthritis.

Fig. 1

The function of MSCs play a significant role in the repair and regeneration process and are identified in this diagram. These include the reduction of cell death to continually replace lost cells, the secretion of trophic factors which stabilise the extracellular matrix and the suppression of immune cell activation to prevent inflammation. Adapted from: BioExplorer.net [63]

Fig. 2

PRISMA flowchart of study selection criteria