In Vivo Generation of Post-infarct Human Cardiac Muscle by Laminin-Promoted Cardiovascular Progenitors

Yap L., Wang J.-W., Moreno-Moral A., de Kleijn D.P.V., Petretto E., Tryggvason K.

Cell Reports, 2019

In this article, the authors report a high reproducible, chemically defined, xeno-free laminin-based differentiation protocol to generate stem cell-derived cardiovascular progenitors (CVPs). Laminin-221 (LN-221) was identified as the most likely expressed cardiac laminin. LN221 promoted the differentiation of pluripotent human embryonic stem cells (hESCs) toward cardiomyocyte lineage and downregulated pluripotency and teratoma-associated genes. Single-cell RNA sequencing of CVPs derived from hESC lines identified three main progenitor subpopulations. These CVPs were transplanted into myocardial infarction mice, where heart function was improved as measured by echocardiogram and human heart muscle bundle formation was identified histologically. This method may provide clinical-quality cells for use in regenerative cardiology.