Mesenchymal stem cell mediates cardiac repair through autocrine, paracrine and endocrine axes
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(2020) 18:336 Sid‑Otmane et al. J Transl Med https://doi.org/10.1186/s12967-020-02504-8
Open Access
REVIEW
Mesenchymal stem cell mediates cardiac repair through autocrine, paracrine and endocrine axes Celia Sid‑Otmane1,3 , Louis P. Perrault1,3,4 and Hung Q. Ly1,2,3*
Abstract In the past decade, despite key advances in therapeutic strategies following myocardial infarction, none can directly address the loss of cardiomyocytes following ischemic injury. Cardiac cell-based therapy is at the cornerstone of regenerative medicine that has shown potential for tissue repair. Mesenchymal stem cells (MSC) represent a strong candidate to heal the infarcted myocardium. While differentiation potential has been described as a possible avenue for MSC-based repair, their secreted mediators are responsible for the majority of the ascribed prohealing effects. MSC can either promote their own survival and proliferation through autocrine effect or secrete trophic factors that will act on adjacent cells through a paracrine effect. Prior studies have also documented beneficial effects even when MSCs were remotely delivered, much akin to an endocrine mechanism. This review aims to distinguish the paracrine activity of MSCs from an endocrine-like effect, where remotely transplanted cells can promote healing of the injured myocardium. Keywords: Paracrine, Autocrine, Endocrine, Mesenchymal stem cells, Remote delivery Background Ischemic heart disease (IHD) due to coronary artery disease remains a serious burden on health systems across Western countries. Medical advances and device-based therapies have impacted mortality and improved quality of life of such patients [1]. These therapies are designed to rescue the ischemic but viable tissue only and fail to address the key molecular targets participating in the pathological cardiac remodeling [2]. Cardiomyocytes being terminally differentiated with minimal regenerative ability (0.5–2%), cardiac transplantation remains the only true cure for failing hearts [3]. However, the limited number of available donors limits the impact of such a therapeutic avenue. Tissue regeneration has emerged as a
*Correspondence: [email protected] 3 Research Centre, Montreal Heart Institute, Université de Montréal, 5000 Belanger Street, Montreal, QC H1T 1C8, Canada Full list of author information is available at the end of the article
promising field of research using mainly cell-based therapy [4]. Embryonic and adult stem cells are capable of generating new tissue through differentiation into multiple lineages. Embryonic stem cells (ESC) isolated from the inner cell mass of blastocytes are pluripotent and capable of generating the three germinal layers [5]. However ethical issues and teratoma formation limit their clinical use. Induced pluripotent stem cells (iPSC) have very similar characteristics to ESC where terminally differentiated cells have been used to generate pluripotent cells [6]. Clinical translation of iPSC overcomes ethical issues related to ESC but security concerns with teratoma formatio
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