Reprogramming of fibroblasts into expandable cardiovascular progenitor cells via small molecules in xeno-free conditions

Wang, Jia; Gu, Shanshan; Liu, Fang; Chen, Zihao; He, Xu; Liu, Zhun; Cheng, Weisheng; Wu, Linwei; Xu, Tao; Chen, Zhongyan; Chen, Ding; Chen, Xuena; Zeng, Fanzhu; Zhao, Zhiju; Zhang, Mingliang; Cao, Nan

doi:10.1038/s41551-022-00865-7

Cited by 22 publications

(14 citation statements)

References 62 publications

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“…Similar to the iCM reprogramming process, small molecules could also contribute to iCPC generation [ 108 ]. The chemically-induced CPCs can be preserved into long-term proliferation.…”

Section: Cardiac Reprogramming For Heart Regenerationmentioning

confidence: 99%

Advances in Cellular Reprogramming-Based Approaches for Heart Regenerative Repair

Liang

Paul

et al. 2022

Cells

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Continuous loss of cardiomyocytes (CMs) is one of the fundamental characteristics of many heart diseases, which eventually can lead to heart failure. Due to the limited proliferation ability of human adult CMs, treatment efficacy has been limited in terms of fully repairing damaged hearts. It has been shown that cell lineage conversion can be achieved by using cell reprogramming approaches, including human induced pluripotent stem cells (hiPSCs), providing a promising therapeutic for regenerative heart medicine. Recent studies using advanced cellular reprogramming-based techniques have also contributed some new strategies for regenerative heart repair. In this review, hiPSC-derived cell therapeutic methods are introduced, and the clinical setting challenges (maturation, engraftment, immune response, scalability, and tumorigenicity), with potential solutions, are discussed. Inspired by the iPSC reprogramming, the approaches of direct cell lineage conversion are merging, such as induced cardiomyocyte-like cells (iCMs) and induced cardiac progenitor cells (iCPCs) derived from fibroblasts, without induction of pluripotency. The studies of cellular and molecular pathways also reveal that epigenetic resetting is the essential mechanism of reprogramming and lineage conversion. Therefore, CRISPR techniques that can be repurposed for genomic or epigenetic editing become attractive approaches for cellular reprogramming. In addition, viral and non-viral delivery strategies that are utilized to achieve CM reprogramming will be introduced, and the therapeutic effects of iCMs or iCPCs on myocardial infarction will be compared. After the improvement of reprogramming efficiency by developing new techniques, reprogrammed iCPCs or iCMs will provide an alternative to hiPSC-based approaches for regenerative heart therapies, heart disease modeling, and new drug screening.

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“…Similar to the iCM reprogramming process, small molecules could also contribute to iCPC generation [ 108 ]. The chemically-induced CPCs can be preserved into long-term proliferation.…”

Section: Cardiac Reprogramming For Heart Regenerationmentioning

confidence: 99%

Advances in Cellular Reprogramming-Based Approaches for Heart Regenerative Repair

Liang

Paul

et al. 2022

Cells

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“…Notably, the longterm expression of OSKM tends to lead to tumor formation (Chen et al, 2021). A newly isolated culture of expandable cardiovascular progenitor cells (CPCs) was reported with promising characteristics for regenerative medicine (Lalit et al, 2016;Zhang et al, 2016;Wang et al, 2022). These multipotent stem cells exist exclusively in the embryonic development and could subsequently generate heart tissue (Laugwitz et al, 2005).…”

Section: (Table 2)mentioning

confidence: 99%

“…These multipotent stem cells exist exclusively in the embryonic development and could subsequently generate heart tissue ( Laugwitz et al, 2005 ). Recently, CPCs were reported to be obtained by treatment with six small molecules from mouse or human fibroblasts and cultured in chemical define and xeno-free conditions ( Wang et al, 2022 ), which provides a new and abundant cell source for cardiac cell therapy and enhances the clinical application prospects of CPCs.…”

Section: Cardiomyocytesmentioning

confidence: 99%

“…In addition to the chromatin dynamics, cell morphological changes are also a phenomenon that cannot be ignored, which would provide certain guiding significance for the optimization in the process of cellular reprogramming. Mesenchymal-to-epithelial transitions (MET) or the opposite process EMT could provide a kind of that conceptual framework ( Li et al, 2010 ; Zhao et al, 2015 ; Li Q. et al, 2017 ; Wang et al, 2022 ) to investigate the underlying mechanism and improve the strategy for reprogramming.…”

Section: Principles Of Cell Reprogrammingmentioning

confidence: 99%

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The Art of Reprogramming for Regenerative Medicine

Kuang

Huang

Pei

2022

Front. Cell Dev. Biol.

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Traditional pharmaceuticals in the forms of small chemical compounds or macromolecules such as proteins or RNAs have provided lifesaving solutions to many acute and chronic conditions to date. However, there are still many unmet medical needs, especially those of degenerative nature. The advent of cell-based therapy holds the promise to meet these challenges. In this review, we highlight a relatively new paradigm for generating or regenerating functional cells for replacement therapy against conditions such as type I diabetes, myocardial infarction, neurodegenerative diseases and liver fibrosis. We focus on the latest progresses in cellular reprogramming for generating diverse functional cell types. We will also discuss the mechanisms involved and conclude with likely general principles underlying reprogramming.

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“…This protocol provides a method for reprogramming of fibroblasts into expandable CPCs without introducing genetic manipulation. 1 Nevertheless, there are still limitations that should be overcome before the method can be widely used for future clinical translation.…”

Section: Limitationsmentioning

confidence: 99%

Generation of expandable cardiovascular progenitor cells from mouse and human fibroblasts via direct chemical reprogramming

Wang¹,

Wang

Cao

2022

STAR Protocols

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Reprogramming of fibroblasts into expandable cardiovascular progenitor cells via small molecules in xeno-free conditions

Cited by 22 publications

References 62 publications

Advances in Cellular Reprogramming-Based Approaches for Heart Regenerative Repair

Advances in Cellular Reprogramming-Based Approaches for Heart Regenerative Repair

The Art of Reprogramming for Regenerative Medicine

Generation of expandable cardiovascular progenitor cells from mouse and human fibroblasts via direct chemical reprogramming

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