Bone Marrow-Derived CD133+ Cells in Ischemic Heart Disease: Clinical Evidence, Paracrine Mechanisms, and Potency Assessment

Background: Bone marrow-derived CD133⁺ cells have been tested as autologous products in acute and chronic ischaemic heart disease, but their mechanism and clinical value remain uncertain. Objective: To map the clinical, mechanistic, manufacturing, and regulatory evidence for bone marrow-derived immunoselected CD133+ products and identify gaps relevant to potency assessment. Methods: PubMed and Europe PMC were searched from inception through August 2026, supplemented by backward citation searching and official regulatory sources. Records were organised in a single-reviewer PRISMA-ScR workflow and charted by evidence domain, cell source, design, delivery/manufacturing context, endpoints, and limitations. Results: The searches yielded 482 database records and 18 additional sources. After the removal of 289 duplicates, 211 unique records were screened, and 57 sources were included: 35 clinical reports, six direct preclinical/mechanistic studies, six manufacturing/quality studies, five contextual mechanistic studies, and five guidance/regulatory documents. Clinical studies support feasibility and limited-population safety but show no consistent improvement in global ventricular function or clinical outcomes. Direct adult bone marrow CD133+ mechanistic evidence remains sparse, while RECARDIO provides an associative product-to-perfusion bridge. Conclusions: A mechanism-linked potency strategy should prioritise source-specific endothelial rescue under hypoxia–reoxygenation, supported by migration, network formation, and a restricted directional secretome panel. Prospective product-to-perfusion validation is required before CD133+ therapy can be considered clinically established.