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

Lynn Yap | Zendy; JiongWei Wang | Zendy; Aida MorenoMoral | Zendy; Li Yen Chong | Zendy; Yi Sun | Zendy; Nathan Harmston | Zendy; Xiaoyuan Wang | Zendy; Suet Yen Chong | Zendy; Konstantinos Vanezis | Zendy; Miina K. Öhman | Zendy; Heming Wei | Zendy; Ralph M. Bunte | Zendy; Sujoy Gosh | Zendy; Stuart A. Cook | Zendy; Outi Hovatta | Zendy; Dominique P.V. de Kleijn | Zendy; Enrico Petretto | Zendy; Karl Tryggvason | Zendy

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

Author(s) -

Lynn Yap,

JiongWei Wang,

Aida MorenoMoral,

Li Yen Chong,

Yi Sun,

Nathan Harmston,

Xiaoyuan Wang,

Suet Yen Chong,

Konstantinos Vanezis,

Miina K. Öhman,

Heming Wei,

Ralph M. Bunte,

Sujoy Gosh,

Stuart A. Cook,

Outi Hovatta,

Dominique P.V. de Kleijn,

Enrico Petretto,

Karl Tryggvason

Publication year - 2019

Publication title -

cell reports

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 6.264

H-Index - 154

eISSN - 2639-1856

pISSN - 2211-1247

DOI - 10.1016/j.celrep.2019.02.083

Subject(s) - embryonic stem cell , progenitor cell , biology , laminin , microbiology and biotechnology , induced pluripotent stem cell , in vivo , cellular differentiation , p19 cell , regeneration (biology) , myocyte , stem cell , gene , biochemistry , extracellular matrix , genetics

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.

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