Cyclosporin-A potently induces highly cardiogenic progenitors from embryonic stem cells

Yan, Peishi; Nagasawa, Atsushi; Uosaki, Hideki; Sugimoto, Akihiro; Yamamizu, Kohei; Teranishi, Mizue; Matsuda, Hiroyuki; Matsuoka, Satoshi; Ikeda, Tadashi; Komeda, Masashi; Sakata, Ryuzo; Yamashita, Jun

doi:10.1016/j.bbrc.2008.12.019

Cited by 43 publications

(57 citation statements)

References 20 publications

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“…S1A). Cyclosporin-A (3 lg/ml) was added to Flk1 þ cell culture to promote CM differentiation [37]. For the differentiation of ECs or MCs, purified Flk1 þ cells were plated onto gelatin-coated dishes and then cultured with DM in the presence of VEGF 165 (50 ng/ml) and 8-bromoadenosine-3 0 : 5 0 -cyclic monophosphate sodium salt (8bromo-cAMP) (0.5 mmol/l) (Supporting Information Fig.…”

Section: Cell Differentiationmentioning

confidence: 99%

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Pluripotent Stem Cell-Engineered Cell Sheets Reassembled with Defined Cardiovascular Populations Ameliorate Reduction in Infarct Heart Function Through Cardiomyocyte-Mediated Neovascularization

et al. 2012

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Although stem cell therapy is a promising strategy for cardiac restoration, the heterogeneity of transplanted cells has been hampering the precise understanding of the cellular and molecular mechanisms. Previously, we established a cardiovascular cell differentiation system from mouse pluripotent stem cells, in which cardiomyocytes (CMs), endothelial cells (ECs), and mural cells (MCs) can be systematically induced and purified. Combining this with cell sheet technology, we generated cardiac tissue sheets reassembled with defined cardiovascular populations. Here, we show the potentials and mechanisms of cardiac tissue sheet transplantation in cardiac function after myocardial infarction (MI). Transplantation of the cardiac tissue sheet to a rat MI model showed significant and sustained improvement of systolic function accompanied by neovascularization. Reduction of the infarct wall thinning and fibrotic length indicated the attenuation of left ventricular remodeling. Cell tracing with species-specific fluorescent in situ hybridization after transplantation revealed a relatively early loss of transplanted cells and an increase in endogenous neovascularization in the proximity of the graft, suggesting an indirect angiogenic effect of cardiac tissue sheets rather than direct CM contributions. We prospectively dissected the functional mechanisms with cell type-controlled sheet analyses. Sheet CMs were the main source of vascular endothelial growth factor. Transplantation of sheets lacking CMs resulted in the disappearance of neovascularization and subsequent functional improvement, indicating that the beneficial effects of the sheet were achieved by sheet CMs. ECs and MCs enhanced the sheet functions and structural integration. Supplying CMs to ischemic regions with cellular interaction could be a strategic key in future cardiac cell therapy.

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Section: Cell Differentiationmentioning

confidence: 99%

“…CMs were differentiated and purified as previously reported [30,37]. Briefly, when Flk1 þ cells derived from mouse ESCs carrying cardiacspecific GFP gene are cultured on OP9 stroma cells, spontaneously beating CMs (GFP þ ) can be induced and subsequently purified by FACS.…”

Section: Construction and Characterization Of Cardiac Tissue Sheetmentioning

confidence: 99%

Pluripotent Stem Cell-Engineered Cell Sheets Reassembled with Defined Cardiovascular Populations Ameliorate Reduction in Infarct Heart Function Through Cardiomyocyte-Mediated Neovascularization

et al. 2012

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“…Embryonic stem cells and, more recently, induced Pluripotent Stem cells (iPS) have been shown to be able to differentiate in vitro into genuine cardiomyocytes ( Figure 7) and supportive cardiac cells (Passier et al 2008;Narazaki et al 2008) as well as to integrate into heart tissue, improving cardiac function (Yan et al 2009;Laflamme et al 2007). However, ES and iPS also have disadvantages that may limit their use in clinical settings.…”

Section: Valvular Heart Diseasementioning

confidence: 99%

Isolation, Characterization and Differentiation Potential of Cardiac Progenitor Cells in Adult Pigs

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Maffei

et al. 2012

Stem Cell Rev and Rep

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“…88 Very recently, mouse cardiac progenitor cells could be derived from ES cells with high efficiency by addition of cyclosporin A to embryoid bodies. 89 Moreover, these cardiac progenitors, transplanted in a chronic myocardial infarction model of rat, successfully differentiated into cardiomyocytes and integrated in the infarcted heart. Recently, in a screen of 4000 compounds, two cell-permeable small molecules were identified that direct differentiation of ESCs into the endodermal lineage.…”

Section: Chemistry and Cell Reprogrammingmentioning

confidence: 99%

Cell reprogramming: expectations and challenges for chemistry in stem cell biology and regenerative medicine

et al. 2010

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The possibility of reprogramming adult somatic cells into pluripotent stem cells (iPSCs) has generated a renewed interest into stem cell research and promises to overcome several key issues, including the ethical concerns of using human embryonic stem cells and the difficulty of obtaining large numbers of adult stem cells (Belmonte et al., Nat Rev Genet, 2009). This approach is also not free from challenges like the mechanism of the reprogramming process, which has yet to be elucidated, and the warranties for safety of generated pluripotent cells, especially in view of their possible therapeutic use. Very recently, several new reprogramming methods have surfaced, which seem to be more appropriate than genetic reprogramming. Particularly, chemically induced pluripotent cells (CiPSs), obtained with recombinant proteins or small synthetic molecules, may represent a valid approach, simpler and possibly safer than the other ones.

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Cyclosporin-A potently induces highly cardiogenic progenitors from embryonic stem cells

Cited by 43 publications

References 20 publications

Pluripotent Stem Cell-Engineered Cell Sheets Reassembled with Defined Cardiovascular Populations Ameliorate Reduction in Infarct Heart Function Through Cardiomyocyte-Mediated Neovascularization

Pluripotent Stem Cell-Engineered Cell Sheets Reassembled with Defined Cardiovascular Populations Ameliorate Reduction in Infarct Heart Function Through Cardiomyocyte-Mediated Neovascularization

Isolation, Characterization and Differentiation Potential of Cardiac Progenitor Cells in Adult Pigs

Cell reprogramming: expectations and challenges for chemistry in stem cell biology and regenerative medicine

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