TY - JOUR
T1 - Metabolic environment in vivo as a blueprint for differentiation and maturation of human stem cell-derived cardiomyocytes
AU - Slaats, Rolf H.
AU - Schwach, Verena
AU - Passier, Robert
N1 - Elsevier deal
PY - 2020/10/1
Y1 - 2020/10/1
N2 - Patient-derived human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) are increasingly being used for disease modeling, drug screening and regenerative medicine. However, to date, an immature, fetal-like, phenotype of hPSC-CMs restrains their full potential. Increasing evidence suggests that the metabolic state, particularly important for provision of sufficient energy in highly active contractile CMs and anabolic and regulatory processes, plays an important role in CM maturation, which affects crucial functional aspects of CMs, such as contractility and electrophysiology. During embryonic development the heart is subjected to metabolite concentrations that differ substantially from that of hPSC-derived cardiac cell cultures. A deeper understanding of the environmental and metabolic cues during embryonic heart development and how these change postnatally, will provide a framework for optimizing cell culture conditions and maturation of hPSC-CMs. Maturation of hPSC-CMs will improve the predictability of disease modeling, drug screening and drug safety assessment and broadens their applicability for personalized and regenerative medicine.
AB - Patient-derived human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) are increasingly being used for disease modeling, drug screening and regenerative medicine. However, to date, an immature, fetal-like, phenotype of hPSC-CMs restrains their full potential. Increasing evidence suggests that the metabolic state, particularly important for provision of sufficient energy in highly active contractile CMs and anabolic and regulatory processes, plays an important role in CM maturation, which affects crucial functional aspects of CMs, such as contractility and electrophysiology. During embryonic development the heart is subjected to metabolite concentrations that differ substantially from that of hPSC-derived cardiac cell cultures. A deeper understanding of the environmental and metabolic cues during embryonic heart development and how these change postnatally, will provide a framework for optimizing cell culture conditions and maturation of hPSC-CMs. Maturation of hPSC-CMs will improve the predictability of disease modeling, drug screening and drug safety assessment and broadens their applicability for personalized and regenerative medicine.
KW - UT-Hybrid-D
KW - Fatty acid
KW - hPSC-cardiomyocytes
KW - Maturation
KW - Metabolism
KW - Cardiac development
UR - http://www.scopus.com/inward/record.url?scp=85086987536&partnerID=8YFLogxK
U2 - 10.1016/j.bbadis.2020.165881
DO - 10.1016/j.bbadis.2020.165881
M3 - Review article
C2 - 32562698
AN - SCOPUS:85086987536
VL - 1866
JO - Biochimica et biophysica acta. Molecular basis of disease
JF - Biochimica et biophysica acta. Molecular basis of disease
SN - 0925-4439
IS - 10
M1 - 165881
ER -