• Rapamycin reduces senescence and fibrosis markers in OA chondrocytes without compromising chondrogenic markers.
• Rapamycin enhances AD-MSC chondrogenic differentiation and suppresses adipogenic differentiation.
• Rapamycin boosts AD-MSC immunomodulatory functions by upregulating IDO1, PTGS2, and PD-L1.
• The combination of rapamycin and AD-MSCs improves chondroprotective effects on OA chondrocytes, suggesting a promising therapeutic strategy.