Cardiotoxicity evaluation using human embryonic stem cells and induced pluripotent stem cell-derived cardiomyocytes

Cardiomyocytes derived from embryonic stem cells (ES-CMs) and induced pluripotent stem cells (iPS-CMs) are useful for toxicity and pharmacology screening. In the present study, we found that cardiomyocyte-rich beating cell clusters (CCs) emerged from murine embryonic stem cell (mESC)–derived beating EBs and from human-induced pluripotent stem cell (hiPSC)–derived beating EBs dissociated by gentle pipetting with a thin glass pipette. The percentage of cardiac troponin T (cTnT)–positive cells in the beating CCs obtained from mESC-derived and hiPSC-derived beating EBs was higher (81.5% and 91.6%, respectively) than in beating-undissociated EBs (13.7% and 67.1%, respectively). For mESCs, the yield of cTnT-positive cells from beating CCs was estimated to be 1.6 times higher than that of beating EBs. The bromodeoxyuridine labeling index of mouse ES-CMs and human iPS-CMs in beating CCs was 1.5- and 3.2-fold, respectively, greater than those in beating EBs. To investigate the utility of the cells in toxicity assessment, we showed that doxorubicin, a cardiotoxic drug, induced myofilament disruption in cardiomyocytes isolated by this method. This simple method enables preparation of mouse ES-CMs and human iPS-CMs with better proliferative activity than beating EBs not dissociated by pipetting, and the cardiomyocytes are useful for drug-induced myocardial toxicity testing.

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TGF-β Inhibitor SB431542 Promotes the Differentiation of Induced Pluripotent Stem Cells and Embryonic Stem Cells into Mesenchymal-Like Cells

Stem Cells International ◽

10.1155/2018/7878201 ◽

2018 ◽

Vol 2018 ◽

pp. 1-13 ◽

Cited By ~ 3

Author(s):

Alessander Leyendecker Junior

Keyword(s):

Tissue Engineering ◽

Stem Cells ◽

Mesenchymal Stem Cells ◽

Stem Cell ◽

Embryonic Stem Cells ◽

Pluripotent Stem Cells ◽

Pluripotent Stem Cell ◽

Embryonic Stem ◽

Stem Cell Markers ◽

Induced Pluripotent

Due to their potential for tissue engineering applications and ability to modulate the immune system and reduce inflammation, mesenchymal stem cells (MSCs) have been explored as a promising option for the treatment of chronic diseases and injuries. However, there are problems associated with the use of this type of cell that limit their applications. Several studies have been exploring the possibility to produce mesenchymal stem cells from pluripotent stem cells (PSCs). The aim of these studies is to generate MSCs with advantageous characteristics of both PSCs and MSCs. However, there are still some questions concerning the characteristics of MSCs derived from the differentiation of PSCs that must be answered before they can be used to treat diseases and injuries. The objective of this study was, therefore, to determine if PSCs exposed to SB431542, a TGF-β inhibitor, are able to differentiate to MSCs, judging by morphology, expression of mesenchymal and pluripotent stem cell markers, expression of pluripotency-related genes, and ability to differentiate to osteocytes and adipocytes. The results obtained demonstrated that it is possible to induce the differentiation of both embryonic stem cells and induce pluripotent stem cells into cells with characteristics that highly resemble those from MSCs through the inhibition of the TGF-β pathway.

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Increase of sensitivity to mechanical stimulus after transplantation of murine induced pluripotent stem cell–derived astrocytes in a rat spinal cord injury model

Journal of Neurosurgery Spine ◽

10.3171/2011.7.spine10775 ◽

2011 ◽

Vol 15 (6) ◽

pp. 582-593 ◽

Cited By ~ 24

Author(s):

Koichi Hayashi ◽

Masayuki Hashimoto ◽

Masao Koda ◽

Atsuhiko T. Naito ◽

Atsushi Murata ◽

...

Keyword(s):

Spinal Cord ◽

Stem Cells ◽

Spinal Cord Injury ◽

Stem Cell ◽

Pluripotent Stem Cell ◽

Embryonic Stem ◽

Induced Pluripotent Stem Cell ◽

Mechanical Stimulus ◽

Cord Injury ◽

Induced Pluripotent

Object Clinical use of autologous induced pluripotent stem cells (iPSCs) could circumvent immune rejection and bioethical issues associated with embryonic stem cells. Spinal cord injury (SCI) is a devastating trauma with long-lasting disability, and current therapeutic approaches are not satisfactory. In the present study, the authors used the neural stem sphere (NSS) method to differentiate iPSCs into astrocytes, which were evaluated after their transplantation into injured rat spinal cords. Methods Induced pluripotent stem cell–derived astrocytes were differentiated using the NSS method and injected 3 and 7 days after spinal contusion–based SCI. Control rats were injected with DMEM in the same manner. Locomotor recovery was assessed for 8 weeks, and sensory and locomotion tests were evaluated at 8 weeks. Immunohistological parameters were then assessed. Results Transplant recipients lived for 8 weeks without tumor formation. Transplanted cells stretched their processes along the longitudinal axis, but they did not merge with the processes of host GFAP-positive astrocytes. Locomotion was assessed in 3 ways, but none of the tests detected statistically significant improvements compared with DMEM-treated control rats after 8 weeks. Rather, iPSC transplantation caused even greater sensitivity to mechanical stimulus than DMEM treatment. Conclusions Astrocytes can be generated by serum treatment of NSS-generated cells derived from iPSCs. However, transplantation of such cells is poorly suited for repairing SCI.

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