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

Cell Reports
Lynn YapKarl Tryggvason

Abstract

Regeneration of injured human heart muscle is limited and an unmet clinical need. There are no methods for the reproducible generation of clinical-quality stem cell-derived cardiovascular progenitors (CVPs). We identified laminin-221 (LN-221) as the most likely expressed cardiac laminin. We produced it as human recombinant protein and showed that LN-221 promotes differentiation of pluripotent human embryonic stem cells (hESCs) toward cardiomyocyte lineage and downregulates pluripotency and teratoma-associated genes. We developed a chemically defined, xeno-free laminin-based differentiation protocol to generate CVPs. We show high reproducibility of the differentiation protocol using time-course bulk RNA sequencing developed from different hESC lines. Single-cell RNA sequencing of CVPs derived from hESC lines supported reproducibility and identified three main progenitor subpopulations. These CVPs were transplanted into myocardial infarction mice, where heart function was measured by echocardiogram and human heart muscle bundle formation was identified histologically. This method may provide clinical-quality cells for use in regenerative cardiology.

Citations

Jun 6, 2020·Annual Review of Biomedical Engineering·Erica A CastilloBeth L Pruitt
Aug 4, 2020·World Journal of Stem Cells·Guan ZhengHui-Yong Shen
Aug 27, 2019·Frontiers in Cell and Developmental Biology·Amanda LeitolisMarco A Stimamiglio
Jan 11, 2020·Frontiers in Cardiovascular Medicine·Farhan ChaudhryPhillip D Levy
Aug 28, 2020·Frontiers in Bioengineering and Biotechnology·Pilar MonteroManuel M Mazo
Nov 11, 2019·Trends in Cell Biology·Lynn YapKarl Tryggvason
Mar 7, 2021·Development·Christopher J Derrick, Emily S Noël

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