Comparative repair efficacy of three mesenchymal stem cell sources in rat full-thickness talar cartilage defects

Ankle cartilage damage frequently progresses to osteoarthritis (OA), which impairs patient quality of life and creates substantial socioeconomic burdens worldwide. Mesenchymal stem cells (MSCs) offer a promising approach for cartilage regeneration; however, comparative data on the efficacy of MSCs from different tissue sources for ankle cartilage repair remains limited. As an exploratory preclinical study, this investigation aimed to evaluate and compare the effects of bone marrow-derived MSCs (BMMSCs), adipose-derived MSCs (ADMSCs), and synovial fluid-derived MSCs (SFMSCs) in a rat model of full-thickness talar cartilage defects. Full-thickness talar cartilage defects were created by limited-depth drilling in 8-week-old male Sprague-Dawley rats (200-300 g). Animals were randomly assigned to a control group or three treatment groups receiving intra-articular injection of BMMSCs, ADMSCs, or SFMSCs. Outcomes were assessed using behavioral and gait tests, footprint analysis, Micro-CT imaging for subchondral bone parameters (BS/TV, Tb.N, Tb.Sp), ICRS macroscopic scoring, histopathological evaluation, and immunohistochemical staining for chondrogenic markers (Col II, FSTL1, SOX9, Smad3). In this exploratory analysis, the SFMSC group displayed comparatively better functional recovery in behavioral and gait measurements relative to other groups. The footprint length factor was significantly higher in the SFMSC group (6.76 ± 1.15) than in the control group (5.52 ± 1.68, P < 0.05), and the ICRS score was also elevated in the SFMSC group (11.00 ± 1.26 vs. 8.80 ± 1.32 in controls, P < 0.01). No significant differences in subchondral bone Micro-CT parameters were detected among groups (P > 0.05). Histological and immunohistochemical findings suggested that SFMSCs were associated with enhanced hyaline cartilage formation and relatively higher expression of chondrogenic markers at the defect site. Within the constraints of this exploratory preclinical study, SFMSCs showed comparatively favorable effects on talar cartilage repair in rats relative to BMMSCs and ADMSCs. These preliminary findings support SFMSCs as a promising candidate source for stem cell-based ankle cartilage regeneration, providing exploratory evidence that may inform future investigations toward clinical translation.