• Open Access

Cardiac renewing: interstitial Cajal-like cells nurse cardiomyocyte progenitors in epicardial stem cell niches

Authors

  • L. M. Popescu,

    Corresponding author
    1. Department of Cellular and Molecular Medicine, ‘Carol Davila’ University of Medicine and Pharmacy, Bucharest, Romania
    2. ‘Victor Babes’ National Institute of Pathology, Bucharest, Romania
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  • Mihaela Gherghiceanu,

    1. ‘Victor Babes’ National Institute of Pathology, Bucharest, Romania
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  • C. G. Manole,

    1. Department of Cellular and Molecular Medicine, ‘Carol Davila’ University of Medicine and Pharmacy, Bucharest, Romania
    2. ‘Victor Babes’ National Institute of Pathology, Bucharest, Romania
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  • Maria Simonetta Faussone-Pellegrini

    1. Department of Anatomy, Histology and Forensic Medicine, Section of Histology, University of Florence, Florence, Italy
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  • Re-use of this article is permitted in accordance with the Creative Commons Deed, Attribution 2.5, which does not permit commercial exploitation.

*Correspondence to: L.M. POPESCU, M.D., Ph.D. Department of Cellular and Molecular Medicine, “Carol Davila” University of Medicine and Pharmacy, P.O. Box 35–29, Bucharest 35, Romania.
E-mail: LMP@jcmm.org

Abstract

Recent studies suggested that various cell lineages exist within the subepicardium and we supposed that this area could host cardiac stem cell niches (CSCNs). Using transmission electron microscopy, we have found at least 10 types of cells coexisting in the subepicardium of normal adult mice: adipocytes, fibroblasts, Schwann cells and nerve fibres, isolated smooth muscle cells, mast cells, macrophages, lymphocytes, interstitial Cajal-like cells (ICLCs) and cardiomyocytes progenitors (CMPs). The latter cells, sited in the area of origin of coronary arteries and aorta, showed typical features of either very immature or developing cardiomyocytes. Some of these cells were connected to each other to form columns surrounded by a basal lamina and embedded in a cellular network made by ICLCs. Complex intercellular communication occurs between the ICLCs and CMPs through electron-dense nanostructures or through shed vesicles. We provide here for the first time the ultrastructural description of CSCN in the adult mice myocardium, mainly containing ICLCs and CMPs. The existence of resident CMPs in different developmental stages proves that cardiac renewing is a continuous process. We suggest that ICLCs might act as supporting nurse cells of the cardiac niches and may be responsible for activation, commitment and migration of the stem cells out of the niches. Briefly, not only resident cardiac stem cells but also ICLCs regulate myocyte turnover and contribute to both cardiac cellular homeostasis and endogenous repair/remodelling after injuries.

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