De Novo Human Cardiac Myocytes for Medical Research: Promises and Challenges

Abstract

The advent of cellular reprogramming technology has revolutionized biomedical research. De novo human cardiac myocytes can now be obtained from direct reprogramming of somatic cells (such as fibroblasts), from induced pluripotent stem cells (iPSCs, which are reprogrammed from somatic cells), and from human embryonic stem cells (hESCs). Such de novo human cardiac myocytes hold great promise for in vitro disease modeling and drug screening and in vivo cell therapy of heart disease. Here, we review the technique advancements for generating de novo human cardiac myocytes. We also discuss several challenges for the use of such cells in research and regenerative medicine, such as the immature phenotype and heterogeneity of de novo cardiac myocytes obtained with existing protocols. We focus on the recent advancements in addressing such challenges.

Canonical Wnt signaling promotes pacemaker cell specification of cardiac mesodermal cells derived from mouse and human embryonic stem cells

“…11 Recent advances have greatly improved the yield of cardiomyocytes from ESCs, [12][13][14] which are predominantly of ventricular phenotype. 15 Similarly, enrichment of atrial myocytes from pluripotent stem cells has been reported. 16,17 Enrichment of cardiac pacemaker cells during ESC differentiation could be achieved by suramin treatment, 18 via viral overexpression of TBX3 19 or SHOX2, 20 by CD166 cell isolation, 21 or by isolation of a NKX2.5-negative population.…”

“…Embryonic stem cells (ESCs) can give rise to multiple cardiac lineages, including chamber myocytes and pacemaker cells . Recent advances have greatly improved the yield of cardiomyocytes from ESCs, which are predominantly of ventricular phenotype . Similarly, enrichment of atrial myocytes from pluripotent stem cells has been reported .…”

Genetics and the heart rate response to exercise

“…3 ). One possible method is to perform functional experiments in cardiomyocytes obtained from embryonic stem cells [ 105 ]. In cardiomyocytes, human diseases and risk factors with their underlying genetic contribution can be created in vitro [ 105 ].…”

“…One possible method is to perform functional experiments in cardiomyocytes obtained from embryonic stem cells [ 105 ]. In cardiomyocytes, human diseases and risk factors with their underlying genetic contribution can be created in vitro [ 105 ]. Since cardiomyocyte cell cultures can beat spontaneously [ 105 ], simulating the effect of this genetic contribution allows for investigation of the acute heart rate response to pacing from resting to exercise heart rate levels in small cell cultures.…”

“…In cardiomyocytes, human diseases and risk factors with their underlying genetic contribution can be created in vitro [ 105 ]. Since cardiomyocyte cell cultures can beat spontaneously [ 105 ], simulating the effect of this genetic contribution allows for investigation of the acute heart rate response to pacing from resting to exercise heart rate levels in small cell cultures. In addition, by simulating the effect of this genetic contribution, drugs can be screened against an individual’s full genetic backgrounds to discover information on cardiotoxicity for each individual.…”