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Two Stem Cell Populations Including VSELs and CSCs Detected in the Pericardium of Adult Mouse Heart

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Abstract

Adult mammalian heart is considered to be one of the least regenerative organs as it is not able to initiate endogenous regeneration in response to injury unlike in lower vertebrates and neonatal mammals. Evidence is now accumulating to suggest normal renewal and replacement of cardiomyocytes occurs even in middle-aged and old individuals. But underlying mechanisms leading to this are not yet clear. Do tissue-resident stem cells exist or somatic cells dedifferentiate leading to regeneration? Lot of attention is currently being focused on epicardium as it is involved in cardiac development, lodges multipotent progenitors and is a source of growth factors. Present study was undertaken to study the presence of stem cells in the pericardium. Intact adult mouse heart was subjected to partial enzymatic digestion to collect the pericardial cells dislodged from the surface. Pericardial cells suspension was processed to enrich the stem cells using our recently published protocol. Two populations of stem cells were successfully enriched from the pericardium of adult mouse heart along with distinct ‘cardiospheres’ with cytoplasmic continuity (formed by rapid proliferation and incomplete cytokinesis). These included very small embryonic-like stem cells (VSELs) and slightly bigger ‘progenitors’ cardiac stem cells (CSCs). Expression of pluripotent (Oct-4A, Sox-2, Nanog), primordial germ cells (Stella, Fragilis) and CSCs (Oct-4, Sca-1) specific transcripts was studied by RT-PCR. Stem cells expressed OCT-4, NANOG, SSEA-1, SCA-1 and c-KIT. c-KIT was expressed by cells of different sizes but only smaller CD45−c-KIT+ VSELs possess regenerative potential. Inadvertent loss of stem cells while processing for different experiments has led to misperceptions & controversies existing in the field of cardiac stem cells and requires urgent rectification. VSELs/CSCs have the potential to regenerate damaged cardiac tissue in the presence of paracrine support provided by the mesenchymal stromal cells.

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All data and information generated from the study is provided in the text.

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Acknowledgements

We acknowledge published work of all colleagues working on VSELs towards cardiac repair.

Funding

Core support provided to the lab by Indian Council of medical Research, Government of India, New Delhi.

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Authors and Affiliations

  1. Stem Cell Biology Department, ICMR-National Institute for Research in Reproductive Health, Jehangir Merwanji Street, Parel, Mumbai, 400 012, India

    Deepa Bhartiya, Yash Flora, Diksha Sharma & Subhan Ali Mohammad

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  1. Deepa Bhartiya
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  2. Yash Flora
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  4. Subhan Ali Mohammad
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Contributions

DB conceptualized and planned the study, data interpretation and wrote the manuscript. YF performed all the experiments with help from DS and SAM. All authors read and approved the manuscript.

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Correspondence to Deepa Bhartiya.

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Study was approved by Institute Animal Ethics Committee (IAEC) at NIRRH.

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Not applicable as it is not a clinical study.

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NIRRH manuscript number: RA/967/09–2020.

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We have no competing interests whatsoever.

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Bhartiya, D., Flora, Y., Sharma, D. et al. Two Stem Cell Populations Including VSELs and CSCs Detected in the Pericardium of Adult Mouse Heart. Stem Cell Rev and Rep 17, 685–693 (2021). https://doi.org/10.1007/s12015-021-10119-9

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