CD73-expressing endometrial regenerative cell-derived exosomes mitigate acute cardiac allograft rejection through regulating adenosine metabolism in mice

• ERC-derived exosomes (ERC-exos) suppress acute cardiac allograft rejection by converting AMP to adenosine via CD73, thereby inhibiting CD4+ T-cell activation and Th1 differentiation. • CD73 knockout or exosome inhibition (GW4869) abrogates the immunoregulatory effects of ERCs, confirming the essential role of CD73-exosome-adenosine axis. • The combination of ERC-exos with rapamycin synergistically prolongs allograft survival from 15 to 38 days in a murine transplant model, suggesting a promising therapeutic strategy. • This study highlights a novel cell-free approach using CD73+ exosomes to modulate adenosine metabolism, offering a potential alternative to conventional immunosuppressants with fewer side effects.