Human fetal heart development after mid-term: Morphometry and ultrastructural study

Kim, Ho-Dirk; Kim, Dae-joong; Lee, Injae; Rah, Bong-Jin; Sawa, Yoshiki; Schaper, Jutta

doi:10.1016/0022-2828(92)91862-y

Cited by 102 publications

(75 citation statements)

References 33 publications

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“…It is reported that human CMs derived from fetal hearts do not achieve full ultrastructural maturity and that myofibrillar development continues throughout the entire fetal period. 22 The insufficient maturation of hiPSC-CMs after long-term culture could be explained by several factors. In vitro culturing conditions lack the presence of adjacent non-myocyte proliferating cells, which play an important role in the maturation of CMs via paracrine and humoral signals in vivo.…”

Section: Discussionmentioning

confidence: 99%

Ultrastructural Maturation of Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes in a Long-Term Culture

Kamakura

Makiyama

Sasaki

et al. 2013

Circ J

262

224

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Background:In the short-to mid-term, cardiomyocytes generated from human-induced pluripotent stem cells (hiPSC-CMs) have been reported to be less mature than those of adult hearts. However, the maturation process in a long-term culture remains unknown. Methods and Results:A hiPSC clone generated from a healthy control was differentiated into CMs through embryoid body (EB) formation. The ultrastructural characteristics and gene expressions of spontaneously contracting EBs were analyzed through 1-year of culture after cardiac differentiation was initiated. The 14-day-old EBs contained a low number of myofibrils, which lacked alignment, and immature high-density Z-bands lacking A-, H-, I-, and Mbands. Through the long-term culture up to 180 days, the myofibrils became more tightly packed and formed parallel arrays accompanied by the appearance of mature Z-, A-, H-, and I-bands, but not M-bands. Notably, M-bands were finally detected in 360-day-old EBs. The expression levels of the M-band-specific genes in hiPSC-CMs remained lower in comparison with those in the adult heart. Immunocytochemistry indicated increasing number of MLC2v-positive/MLC2a-negative cells with decreasing number of MLC2v/MLC2a double-positive cells, indicating maturing of ventricular-type CMs. Conclusions:The structural maturation process of hiPSC-CMs through 1-year of culture revealed ultrastructural sarcomeric changes accompanied by delayed formation of M-bands. Our study provides new insight into the maturation process of hiPSC-CMs. (Circ J 2013; 77: 1307 -1314

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Section: Discussionmentioning

confidence: 99%

Ultrastructural Maturation of Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes in a Long-Term Culture

Kamakura

Makiyama

Sasaki

et al. 2013

Circ J

262

224

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“…The underlying mechanism of this switch from hyperplastic to hypertrophic growth is still elusive but it appears to be highly associated with the onset of binucleation. Binucleation is seen in cardiomyocytes of all mammalian species, however, its timing differs slightly between species; beginning in the last third gestation in sheep (Jonker et al 2007b) and human (Kim et al 1992), and shortly after birth in mouse (Li et al 1996) and rat (Soonpaa et al 1996).…”

Section: Cell Division Vs Binucleationmentioning

confidence: 97%

The Cardiomyocyte Cell Cycle in Hypertrophy, Tissue Homeostasis, and Regeneration

Zebrowski

Engel

2013

Reviews of Physiology, Biochemistry and Pharmacology

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Mammalian cardiomyocytes withdraw from the cell cycle shortly after birth. Although the adult heart is unable to regenerate, numerous reports have shown that adult cardiomyocytes exhibit a dynamic range of cell cycle activity under various physiological and pathological conditions. Reason and consequence of cardiomyocyte cell cycle activity remain unclear and have led to a number of misconceptions. Understanding the scenarios in which cycling happens may promote new perspectives on the differentiated state of cardiomyocytes, treatments for hypertrophy, heart regeneration and cancer therapy. In this review we discuss the result of cardiomyocyte cell cycle activity in aging and disease and studies manipulating cardiac cell cycle activity to promote cardiac regeneration. In addition, we focus on cardiomyocyte differentiation, cell cycle exit, and the relationship between ploidy and regenerative potential. Finally, we provide observations that may further advance the goal of inducing adult mammalian heart regeneration through cardiomyocyte proliferation.

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“…14 Both MHC isogenes are downregulated in the fetal and failing hearts, consistent with the observation of decreased myofilament contents in the fetal and failing hearts. 15,16 Others have already reported a decrease in MHC-␣ expression and content in the failing human left ventricle. 14,17 We also found a 30-fold reduction of MHC-␣ in the failing human heart.…”

Section: Anf and Mhc Isoformsmentioning

confidence: 99%

Metabolic Gene Expression in Fetal and Failing Human Heart

et al. 2001

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Background-Previous studies suggest that the failing heart reactivates fetal genes and reverts to a fetal pattern of energy substrate metabolism. We tested this hypothesis by examining metabolic gene expression profiles in the fetal, nonfailing, and failing human heart. Methods and Results-Human left ventricular tissue (apex) was obtained from 9 fetal, 10 nonfailing, and 10 failing adult hearts. Using quantitative reverse transcription-polymerase chain reaction, we measured transcript levels of atrial natriuretic factor, myosin heavy chain-␣ and -␤, and 13 key regulators of energy substrate metabolism, of which 3 are considered "adult" isoforms (GLUT4, mGS, mCPT-I) and 3 are considered "fetal" isoforms (GLUT1, lGS, and lCPT-I), primarily through previous studies in rodent models. Compared with the nonfailing adult heart, steady-state mRNA levels of atrial natriuretic factor were increased in both the fetal and the failing heart. The 2 myosin heavy chain isoforms showed the highest expression level in the nonfailing heart. Transcript levels of most of the metabolic genes were higher in the nonfailing heart than the fetal heart. Adult isogenes predominated in all groups and always showed a greater induction than the fetal isogenes in the nonfailing heart compared with the fetal heart. In the failing heart, the expression of metabolic genes decreased to the same levels as in the fetal heart. Conclusions-In the human heart, metabolic genes exist as constitutive and inducible forms. The failing adult heart reverts to a fetal metabolic gene profile by downregulating adult gene transcripts rather than by upregulating fetal genes.

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Human fetal heart development after mid-term: Morphometry and ultrastructural study

Cited by 102 publications

References 33 publications

Ultrastructural Maturation of Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes in a Long-Term Culture

Ultrastructural Maturation of Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes in a Long-Term Culture

The Cardiomyocyte Cell Cycle in Hypertrophy, Tissue Homeostasis, and Regeneration

Metabolic Gene Expression in Fetal and Failing Human Heart

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