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https://doi.org/10.1038/s41536-023-00302-6
Title: | Pluripotent stem cell-derived committed cardiac progenitors remuscularize damaged ischemic hearts and improve their function in pigs | Authors: | Yap, Lynn Chong, Li Yen Tan, Clarissa Adusumalli, Swarnaseetha Seow, Millie Guo, Jing Cai, Zuhua Loo, Sze Jie Lim, Eric Tan, Ru San Grishina, Elina Soong, Poh Loong Lath, Narayan Ye, Lei Petretto, Enrico Tryggvason, Karl |
Keywords: | Science & Technology Life Sciences & Biomedicine Technology Cell & Tissue Engineering Engineering, Biomedical Cell Biology Engineering IN-VITRO TRANSPLANTATION DIFFERENTIATION CARDIOMYOCYTES THERAPY LAMININ MUSCLE |
Issue Date: | 26-May-2023 | Publisher: | NATURE PORTFOLIO | Citation: | Yap, Lynn, Chong, Li Yen, Tan, Clarissa, Adusumalli, Swarnaseetha, Seow, Millie, Guo, Jing, Cai, Zuhua, Loo, Sze Jie, Lim, Eric, Tan, Ru San, Grishina, Elina, Soong, Poh Loong, Lath, Narayan, Ye, Lei, Petretto, Enrico, Tryggvason, Karl (2023-05-26). Pluripotent stem cell-derived committed cardiac progenitors remuscularize damaged ischemic hearts and improve their function in pigs. NPJ REGENERATIVE MEDICINE 8 (1). ScholarBank@NUS Repository. https://doi.org/10.1038/s41536-023-00302-6 | Abstract: | Ischemic heart disease, which is often associated with irreversibly damaged heart muscle, is a major global health burden. Here, we report the potential of stem cell-derived committed cardiac progenitors (CCPs) have in regenerative cardiology. Human pluripotent embryonic stem cells were differentiated to CCPs on a laminin 521 + 221 matrix, characterized with bulk and single-cell RNA sequencing, and transplanted into infarcted pig hearts. CCPs differentiated for eleven days expressed a set of genes showing higher expression than cells differentiated for seven days. Functional heart studies revealed significant improvement in left ventricular ejection fraction at four and twelve weeks following transplantation. We also observed significant improvements in ventricular wall thickness and a reduction in infarction size after CCP transplantation (p-value < 0.05). Immunohistology analyses revealed in vivo maturation of the CCPs into cardiomyocytes (CM). We observed temporary episodes of ventricular tachyarrhythmia (VT) in four pigs and persistent VT in one pig, but the remaining five pigs exhibited normal sinus rhythm. Importantly, all pigs survived without the formation of any tumors or VT-related abnormalities. We conclude that pluripotent stem cell-derived CCPs constitute a promising possibility for myocardial infarction treatment and that they may positively impact regenerative cardiology. | Source Title: | NPJ REGENERATIVE MEDICINE | URI: | https://scholarbank.nus.edu.sg/handle/10635/245783 | ISSN: | 2057-3995 | DOI: | 10.1038/s41536-023-00302-6 |
Appears in Collections: | Staff Publications Elements |
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