Cardiac Progenitor Cell Transplantation and Functional Recovery in Ischaemic Models

Abstract

Background: Cardiac regenerative medicine was built on the claim that resident c-kit-positive progenitors generate new
cardiomyocytes and restore contractile function in ischaemic myocardium. That claim has since been tested genetically.
Objective: To reconstruct the evidence on progenitor transplantation, distinguish retracted from superseded work, and
assess whether pluripotent-stem-cell-derived cardiomyocytes offer a route to genuine remuscularisation.
Methods: Narrative review of lineage-tracing experiments, preclinical models, randomised trials and retraction records.
Findings: Lineage tracing set the cardiomyogenic contribution of c-kit-positive cells at 0.002-0.04% of cardiomyocytes.
Individual-patient meta-analysis of 12 randomised trials (n = 1252) gave an ejection fraction difference of 0.96% (95% CI -0.2
to 2.1), and 0.0 in discrepancy-free trials. Three cited papers have been retracted.
Conclusions: The evidence supports paracrine and immune mechanisms rather than new muscle from adult progenitors.
Pluripotent-derived cardiomyocytes remuscularise but carry engraftment arrhythmia.