Human adipose-derived mesenchymal stem cells (haMSCs) have shown efficacy in treating osteoarthritis (OA) both preclinically and clinically via intra-articular (IA) injection. However, understanding the mode of action of the cell therapy has been limited by cell tracking capability and correlation between the pharmacokinetics of the injected cells and the intended pharmacodynamics effect. This study aims to explore methodology and to understand in vivo biodistribution of clinical-grade haMSCs labeled with fluorescent dye and injected into an immunocompetent OA rat model.
haMSCs labeled with fluorescent dye were investigated for their proliferation and differentiation capabilities. Labeled cells were used to establish detection threshold of a noninvasive biofluorescent imaging system before the cells (2.5 × 10
In vitro proliferation and differentiation of haMSCs were not affected by the labeling of DiD dye. Detection thresholds of the labeled cells in vitro and in vivo were determined to be 10
The current study represents the first attempt to correlate cell therapy efficacy on OA with the physical presence of the injected haMSCs in the OA model, and demonstrates that human adipose-derived mesenchymal stem cells persisted for 10 weeks locally in the rat joint, coinciding with the efficacy observed. It is postulated that persistence and/or proliferation of the haMSCs in the joint is required in order to exert their functions on promoting joint regeneration and/or cartilage protection, further supporting the safety and feasibility of IA injection of MSCs for the treatment of OA patients.