Regenerative Medicine for the Heart: Perspectives on Stem-Cell Therapy

Cho, Gun Sik; Fernandez, Laviel; Kwon, Chulan

doi:10.1089/ars.2014.6063

Cited by 28 publications

(19 citation statements)

References 163 publications

(129 reference statements)

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“…While they have the potential to model and treat a broad spectrum of human diseases, PSC-derived cells are morphologically and functionally similar to fetal cells. This has become a major and common impediment for their application to model and treat late-onset disorders (Cho et al, 2014; Svendsen, 2013; Tabar and Studer, 2014). …”

Section: Introductionmentioning

confidence: 99%

Neonatal Transplantation Confers Maturation of PSC-Derived Cardiomyocytes Conducive to Modeling Cardiomyopathy

et al. 2017

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SUMMARY Pluripotent stem cells (PSCs) offer unprecedented opportunities for disease modeling and personalized medicine. However, PSC-derived cells exhibit fetal-like characteristics and remain immature in a dish. This has emerged as a major obstacle for their application for late-onset diseases. We previously showed that there is a neonatal arrest of long-term cultured PSC-derived cardiomyocytes (PSC-CMs). Here, we demonstrate that PSC-CMs mature into adult CMs when transplanted into neonatal hearts. PSC-CMs became similar to adult CMs in morphology, structure, and function within a month of the transplantation into rats. The similarity was further supported by single-cell RNA-sequencing analysis. Moreover, this in vivo maturation allowed patient-derived PSC-CMs to reveal the disease phenotype of arrhythmogenic right ventricular cardiomyopathy, which predominantly manifests in adults. This study lays a foundation for understanding human CM maturation and pathogenesis and can be instrumental in PSC-based modeling of adult heart diseases.

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Section: Introductionmentioning

confidence: 99%

Neonatal Transplantation Confers Maturation of PSC-Derived Cardiomyocytes Conducive to Modeling Cardiomyopathy

et al. 2017

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“…Pharyngeal arches are transient, segmented bulges that appear on the craniolateral side of developing embryos 9 , which contain multi-potent cardiac progenitor cells—building blocks to make the heart during embryogenesis 10,11 —in second arches and head muscle progenitors in first arches 8 .…”

Section: Discussionmentioning

confidence: 99%

<em>Ex Vivo</em> Culture of Pharyngeal Arches to Study Heart and Muscle Progenitors and Their Niche

Andersen

Kwon

2015

JoVE

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The pharyngeal mesoderm of developing embryos contributes to broad regions of head and heart musculature. We have developed a novel method to study head and heart progenitor cell development with pharyngeal arches (also known as branchial arches) ex vivo. Using this method, we have recently described that the second pharyngeal arch contains self-renewing heart progenitors and serves as a microenvironment for expansion of the progenitors during mouse heart development. The progenitor cells remain undifferentiated and expansive inside the arch, but quickly become functional cardiomyocytes as they migrate out of the arch. We also reported that first pharyngeal arch contains muscle progenitors giving rise to myotubes after leaving the arch. Here, we demonstrate the procedure for the dissection and ex-vivo culture of first and second pharyngeal arches from developing mouse embryos. The method enables one to study head and heart progenitor/muscle development, including cardiomyocyte and myotube formation in detail ex vivo.

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“…The next significant problem is the source and availability of stem cells. There are three classes (based on origin) of SCs: embryonic stem cells (ESCs), taken from the inner cell mass of blastocyst; foetal stem cells (FSC), taken from foetal tissues, and adult stem cells, taken from the bone marrow, peripheral blood, heart or adipose tissue (Cho et al, 2014, Gimble et al, 2007, Passier et al, 2008, Weber et al, 2012, Lodi et al, 2011. The conventional usage technique of SC culture requires a large volume of these cells and hence also a large volume of reagents.…”

Section: Introductionmentioning

confidence: 99%