Towards optimized rehabilitation with regenerative therapy: A systematic review and meta-analysis on the effects of cell-based injections for knee osteoarthritis.

Abstract

<h4>Purpose</h4>This meta-analysis aimed to determine the effects of intra-articular mesenchymal stem cell (MSC)-based injections on both subjective and objective measures of pain and function in patients with knee osteoarthritis (OA). The secondary purpose was to investigate how injection procedures, patient characteristics and post-injection rehabilitation influence outcomes.<h4>Methods</h4>Studies published up to February 2025 were identified using PubMed, Cochrane Library, EBSCOhost, Embase, Web of Science and OpenGrey. Studies that investigated the effects of intra-articular MSC-based injections on improving outcomes for patients with knee OA compared to control conditions were included in this analysis. Two independent reviewers performed data extraction, and disagreements were settled through a third author.<h4>Results</h4>Thirty-three studies qualified for analysis. Multi-level meta-analysis revealed that MSC-based injections were more effective than controls for improving subjective pain (effect size [ES] = 1.03, p < 0.001) and function (ES = 0.79, p < 0.001). These effects increased with time post-injection (both p < 0.001). Few objective measures of knee function were reported. Meta-analysis revealed no significant effect of MSC-based injections for improving knee flexion range of motion (ES = 0.76, p = 0.166). Follow-up exploratory analyses of moderator variables suggest that non-weightbearing (p = 0.022) and exercise (p = 0.001) may increase the effects of MSC-based injections for improving subjective pain and function, respectively, and that patients who are male (p = 0.049), have a greater BMI (p = 0.047), and have less severe OA (p = 0.029) may demonstrate greater improvements in subjective pain following MSC-based injections.<h4>Conclusions</h4>Intra-articular MSC-based injections may improve subjective pain and symptoms for patients with knee OA. However, the subjective improvements may not translate to improved objective knee function. Future studies should investigate the effects of MSC-based injections on objective knee function and how post-injection rehabilitation and patient characteristics augment the effects of MSC-based injections.<h4>Level of evidence</h4>Level II.