Bone Marrow-Derived CD133+ Cells in Ischemic Heart Disease: Clinical and Paracrine Evidence—A Scoping Review and Proposed Potency Development Framework

Background: Autologous bone marrow-derived CD133+ cells have been investigated in ischemic heart disease, but product identity, biological activity, and clinical efficacy remain distinct questions. Objective: To map clinical and mechanistic evidence and propose a product-specific approach to potency development. Methods: The original search covered PubMed and Europe PMC through 13 August 2026, with citation searching and regulatory sources. Evidence was charted in a single-reviewer scoping workflow. During revision, a structured verification audit cross-linked clinical publications to parent programs and public trial registries using study identifiers, investigators, intervention details, recruitment setting, and reported denominators. No formal risk-of-bias assessment or meta-analysis was performed. Results: The historical search retained 57 sources, including 35 clinical publications. Verification identified one omitted primary clinical report and mapped the original clinical publications to 20 program-level cohorts. Under conservative linkage rules, these published programs represent at least 726 documented participants; this is a descriptive program denominator, not a pooled treatment population. Registry verification also identified direct CD133 programs that were terminated, prematurely ended, or lacked a linked peer-reviewed outcome report. Clinical findings remain heterogeneous, and the descriptive map does not establish overall efficacy or an acceptable safety profile. The RECARDIO secretome correlations involved nine patients and culture-expanded samples and support exploratory candidate selection only. Conclusions: The proposed framework separates immediate product controls from slower functional characterization and prospective clinical validation. Context of use, assay performance, manufacturing turnaround, and independent product–patient validation must be established before a candidate measurement can support a potency claim. Residual limitations include the absence of the original record-level exclusion log and lack of direct retrospective searching of subscription bibliographic databases not available to the review team.