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Query: UMLS:C0029713 (
immaturity
)
4,335
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Pluripotent stem cell-derived cardiomyocytes (CMs) have great potential in the development of new therapies for cardiovascular disease. In particular, human induced pluripotent stem cells (iPSCs) may prove especially advantageous due to their pluripotency, their self-renewal potential, and their ability to create patient-specific cell lines. Unfortunately, pluripotent stem cell-derived CMs are immature, with characteristics more closely resembling fetal CMs than adult CMs, and this
immaturity
has limited their use in drug screening and cell-based therapies. Extracellular matrix (ECM) influences cellular behavior and maturation, as does the geometry of the environment-two-dimensional (2D) versus three-dimensional (3D). We therefore tested the hypothesis that native cardiac ECM and 3D cultures might enhance the maturation of iPSC-derived CMs in vitro. We demonstrate that maturation of iPSC-derived CMs was enhanced when cells were seeded into a 3D cardiac ECM scaffold, compared with 2D culture. 3D cardiac ECM promoted increased expression of calcium-handling genes, Junctin, CaV1.2,
NCX1
, HCN4, SERCA2a, Triadin, and CASQ2. Consistent with this, we find that iPSC-derived CMs in 3D adult cardiac ECM show increased calcium signaling (amplitude) and kinetics (maximum upstroke and downstroke) compared with cells in 2D. Cells in 3D culture were also more responsive to caffeine, likely reflecting an increased availability of calcium in the sarcoplasmic reticulum. Taken together, these studies provide novel strategies for maturing iPSC-derived CMs that may have applications in drug screening and transplantation therapies to treat heart disease.
...
PMID:Three-Dimensional Adult Cardiac Extracellular Matrix Promotes Maturation of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes. 2739 82
Human induced pluripotent stem cells derived cardiomyocytes (hiPSC-CMs) have been extensively used for in vitro modeling of human cardiovascular disease, drug screening and pharmacotherapy, but little rigorous studies have been reported on their biophysical or Ca
2+
signaling properties. There is also considerable concern as to the level of their maturity and whether they can serve as reliable models for adult human cardiac myocytes. Ultrastructural difference such as lack of t-tubular network, their polygonal shapes, disorganized sarcomeric myofilament, and their rhythmic automaticity, among others, have been cited as evidence for
immaturity
of hiPSC-CMs. In this review, we will deal with Ca
2+
signaling, its regulation, and its stage of maturity as compared to the mammalian adult cardiomyocytes. We shall summarize the data on functional aspects of Ca
2+
signaling and its parameters that include: L-type calcium channel (Cav1.2), I
Ca
-induced Ca
2+
release, CICR, and its parameters, cardiac Na/Ca exchanger (
NCX1
), the ryanodine receptors (RyR2), sarco-reticular Ca
2+
pump, SERCA2a/PLB, and the contribution of mitochondrial Ca
2+
to hiPSC-CMs excitation-contraction (EC)-coupling as compared with adult mammalian cardiomyocytes. The comparative studies suggest that qualitatively hiPSC-CMs have similar Ca
2+
signaling properties as those of adult cardiomyocytes, but quantitative differences do exist. This review, we hope, will allow the readers to judge for themselves to what extent Ca
2+
signaling of hiPSC-CMs represents the adult form of this signaling pathway, and whether these cells can be used as good models of human cardiomyocytes.
...
PMID:Ca
2+
signaling of human pluripotent stem cells-derived cardiomyocytes as compared to adult mammalian cardiomyocytes. 3258 8
