• MSCs offer a dual therapeutic role in ITP by modulating immune responses and repairing the bone marrow niche, addressing both platelet destruction and production.
• Patient-derived MSCs exhibit intrinsic functional abnormalities, including impaired regulation of macrophage polarization, which can be corrected by exogenous MSC administration.
• The HMGB1-TLR4 pathway is identified as a potential target to restore the immunoregulatory function of BMSCs in ITP.
• Optimization strategies such as tissue source selection, culture conditions, priming, and cellular engineering are crucial for enhancing MSC therapeutic efficacy and safety.