2005
DOI: 10.1196/annals.1341.006
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Functional Properties of Human Embryonic Stem Cell‐Derived Cardiomyocytes

Abstract: Regeneration of the diseased myocardium by cardiac cell transplantation is an attractive therapeutic modality. Yet, because the transplanted cardiomyocytes should functionally integrate within the diseased myocardium, it is preferable that their properties resemble those of the host. To determine the functional adaptability of human embryonic stem cell-derived cardiomyocytes (hESC-CM) to the host myocardium, the authors investigated the excitation-contraction (E-C) coupling and the responsiveness to common phy… Show more

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Cited by 52 publications
(41 citation statements)
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References 32 publications
(61 reference statements)
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“…We therefore suggest that the differences that we observed with respect to the stimulatory effect of caffeine at day 8, but not at day 12, might be likewise due to a small (and potentially variable) fraction of cells that respond to caffeine during early differentiation; or perhaps due to the transient expression of functional RyRs around day 8, which is lost by day 12. Our findings, however, reinforce the previous observation that RyRs are underdeveloped and largely nonfunctional in the SR of these early differentiated cardiomyocytes (Dolnikov et al, 2005).…”
Section: Determination Of the Presence Of Functional Ip 3 Rs And Ryrssupporting
confidence: 78%
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“…We therefore suggest that the differences that we observed with respect to the stimulatory effect of caffeine at day 8, but not at day 12, might be likewise due to a small (and potentially variable) fraction of cells that respond to caffeine during early differentiation; or perhaps due to the transient expression of functional RyRs around day 8, which is lost by day 12. Our findings, however, reinforce the previous observation that RyRs are underdeveloped and largely nonfunctional in the SR of these early differentiated cardiomyocytes (Dolnikov et al, 2005).…”
Section: Determination Of the Presence Of Functional Ip 3 Rs And Ryrssupporting
confidence: 78%
“…The lack of response to caffeine on day 12 might have been due to the holo-f-aequorin having been inactivated, however, the use of Triton X-100 at the end of each experiment confirmed that sufficient active holo-f-aequorin was being expressed by the cells to reveal any distinct signals that were generated. Such an overall lack of response to caffeine has previously been reported in 45 to 60 day old cardiomyocytes derived from H9.2 hESCs (Dolnikov et al, 2005). More recently, caffeine was shown to induce Ca 2+ release in hES2-derived cardiomyocytes but only in a sub-population (~38%) of these cells when they were at day 18 to 24 (Liu et al, 2007).…”
Section: Determination Of the Presence Of Functional Ip 3 Rs And Ryrsmentioning
confidence: 86%
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“…When beating areas of EBs are dissected, they exhibit heterogeneous electro-physiological properties and are prone to triggered arrhythmias [88]. The contractions of ESC-derived myocytes depend on transsarcolemmal calcium influx rather than calcium-induced calcium release from the sarcoplasmic reticulum, which is an expectable outcome given their early developmental stage [89]. Lack of expression of such calcium-handling proteins, as phospholamban and calse-questrin [90], further attests to the immature capacity of the sarcoplasmic reticulum in the ESC.…”
Section: Incomplete Coupling and Ensuing Heterogeneity Pose A Risk Ofmentioning
confidence: 99%
“…Embryonic stem cells (ESCs) have several features that make them an excellent candidate for cardiac cell therapy: (1) Embryonic stem cells can form true cardiomyocytes 62 with a distinct electrophysiological 63 and contractile phenotype 64 and (2) they have an unlimited proliferation potential. 65 Several studies have demonstrated the feasibility of transplantating ESCs in vivo, using mouse as well as human 66 ESCs.…”
Section: The Futurementioning
confidence: 99%