Recent Progress Using Pluripotent Stem Cells for Cardiac Regenerative Therapy

Ichimura, Hajime; Shiba, Yuji

doi:10.1253/circj.cj-17-0400

Cited by 14 publications

(5 citation statements)

References 84 publications

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“…The use of expandable human pluripotent stem cells (hPSCs) with their plasticity in response to developmental signals is a promising and logical choice for many disease therapies ( Carpenter et al., 2009 , Cheng et al., 2014 , Ichimura and Shiba, 2017 ) and for modeling monogenic diseases ( Ebert et al., 2009 , Shi et al., 2017 ). This includes making kidney cells to model ESKDs, or for therapy.…”

Section: Introductionmentioning

confidence: 99%

Generation of Functioning Nephrons by Implanting Human Pluripotent Stem Cell-Derived Kidney Progenitors

Bantounas¹,

Ranjzad²,

Zakaria³

et al. 2018

Stem Cell Reports

159

166

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SummaryHuman pluripotent stem cells (hPSCs) hold great promise for understanding kidney development and disease. We reproducibly differentiated three genetically distinct wild-type hPSC lines to kidney precursors that underwent rudimentary morphogenesis in vitro. They expressed nephron and collecting duct lineage marker genes, several of which are mutated in human kidney disease. Lentiviral-transduced hPSCs expressing reporter genes differentiated similarly to controls in vitro. Kidney progenitors were subcutaneously implanted into immunodeficient mice. By 12 weeks, they formed organ-like masses detectable by bioluminescence imaging. Implants included perfused glomeruli containing human capillaries, podocytes with regions of mature basement membrane, and mesangial cells. After intravenous injection of fluorescent low-molecular-weight dextran, signal was detected in tubules, demonstrating uptake from glomerular filtrate. Thus, we have developed methods to trace hPSC-derived kidney precursors that formed functioning nephrons in vivo. These advances beyond in vitro culture are critical steps toward using hPSCs to model and treat kidney diseases.

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Section: Introductionmentioning

confidence: 99%

Generation of Functioning Nephrons by Implanting Human Pluripotent Stem Cell-Derived Kidney Progenitors

Bantounas¹,

Ranjzad²,

Zakaria³

et al. 2018

Stem Cell Reports

159

166

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“…In the following phase, cardiac specification and maturation are driven by Dickkopf and Noggin—antagonists of the WNT and BMP pathways, respectively. Also, various well-characterised small-molecule compounds can be employed to imitate cellular responses to naturally occurring protein ligands involved in the aforementioned signalling pathways 2 – 4 . 12-O-Tetradecanoylphorbol-13-acetate (TPA) is a very potent small-molecule compound.…”

Section: Introductionmentioning

confidence: 99%

12-O-Tetradecanoylphorbol-13-acetate increases cardiomyogenesis through PKC/ERK signaling

Radaszkiewicz

Beckerová

Woloszczuková

et al. 2020

Sci Rep

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12-O-Tetradecanoylphorbol-13-acetate (TPA) is the most widely used diacylglycerol (DAG) mimetic agent and inducer of protein kinase C (PKC)-mediated cellular response in biomedical studies. TPA has been proposed as a pluripotent cell differentiation factor, but results obtained have been inconsistent. In the present study we show that TPA can be applied as a cardiomyogenesis-promoting factor for the differentiation of mouse embryonic stem (mES) cells in vitro. The mechanism of TPA action is mediated by the induction of extracellular signal-regulated kinase (ERK) activity and the subsequent phosphorylation of GATA4 transcription factor. Interestingly, general mitogens (FGF, EGF, VEGF and serum) or canonical WNT signalling did not mimic the effect of TPA. Moreover, on the basis of our results, we postulate that a TPA-sensitive population of cardiac progenitor cells exists at a certain time point (after days 6–8 of the differentiation protocol) and that the proposed treatment can be used to increase the multiplication of ES cell-derived cardiomyocytes.

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“…Clinical researches are underway in the field of cardiac regenerative medicine utilizing pluripotent stem cell-derived cardiomyocytes, and the presence of a percentage of cTnT-negative cells in the cell population prepared for clinical studies was reported, underscoring the importance of purity control 24 . In the realm of regenerative medicine, preference is given to methods that minimize the likelihood of causing genomic alterations, such as those employing episomal vectors 25 . One commonly employed selection technique, which does not involve genetic modification, is the use of a glucose-free medium 10 .…”

Section: Discussionmentioning

confidence: 99%

Low-adhesion culture selection for human iPS cell-derived cardiomyocytes

Kikuchi,

Matsuura,

Shimizu

2024

Sci Rep

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Despite progress in generating cardiomyocytes from pluripotent stem cells, these populations often include non-contractile cells, necessitating cardiomyocyte selection for experimental purpose. This study explores a novel cardiomyocyte enrichment mechanism: low-adhesion culture selection. The cardiac cells derived from human induced pluripotent stem cells were subjected to a coating-free low-adhesion culture using bovine serum albumin and high molecular weight dextran sulfate. This approach effectively increased the population of cardiac troponin T-positive cardiomyocytes. Similar results were obtained with commercially available low-adhesion culture dishes. Subsequently, we accessed the practicality of selection of cardiomyocytes using this phenomenon by comparing it with established methods such as glucose-free culture and selection based on puromycin resistance genes. The cardiomyocytes enriched through low-adhesion culture selection maintained autonomous pulsation and responsiveness to beta-stimuli. Moreover, no significant differences were observed in the expression of genes related to subtype commitment and maturation when compared to other selection methods. In conclusion, cardiomyocytes derived from pluripotent stem cells were more low-adhesion culture resistant than their accompanying non-contractile cells, and low-adhesion culture is an alternative method for selection of pluripotent stem cell-derived cardiomyocytes.

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Recent Progress Using Pluripotent Stem Cells for Cardiac Regenerative Therapy

Cited by 14 publications

References 84 publications

Generation of Functioning Nephrons by Implanting Human Pluripotent Stem Cell-Derived Kidney Progenitors

Generation of Functioning Nephrons by Implanting Human Pluripotent Stem Cell-Derived Kidney Progenitors

12-O-Tetradecanoylphorbol-13-acetate increases cardiomyogenesis through PKC/ERK signaling

Low-adhesion culture selection for human iPS cell-derived cardiomyocytes

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