DOI: 10.1101/478883Nov 26, 2018Paper

In vivo generation of post-infarct mouse cardiac muscle by cardiomyocyte progenitors produced with a reproducible laminin-promoted human stem cell differentiation system

BioRxiv : the Preprint Server for Biology
Lynn YapKarl Tryggvason

Abstract

Regeneration of human heart muscle after injury is extremely limited and an unmet clinical need. Despite extensive research, there are no methods for the reproducible generation of clinical quality stem-cell-derived cardiovascular progenitors (CVPs). Here, we identified laminin-221 (LN-221) as the main cardiac laminin, which was produced here as human recombinant protein, and showed that LN- 221 promotes differentiation of pluripotent hESCs towards cardiomyocyte lineage and downregulates genes associated with pluripotency and teratoma development. We developed a chemically defined, xeno-free laminin-based cardiomyocyte differentiation protocol to reproducibly generate CVPs that form human muscle in vivo. We assessed the reproducibility of the differentiation protocol using time- course bulk RNA sequencing developed from two different hESC lines. Single-cell RNA sequencing of CVPs derived from two hESC lines further showed high 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 u...Continue Reading

Related Concepts

Cardiovascular Diseases
Cell Differentiation Process
Down-Regulation
Echocardiography
Genes
Heart
Infarction
Laminin
Laboratory mice
Muscle

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