Mesenchymal stem cell mediates cardiac repair through autocrine, paracrine and endocrine axes

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: Autocrine; Endocrine; Mesenchymal stem cells; Paracrine; Remote delivery.

Fig. 1

Cardiac healing and repair mediated by direct and indirect mechanisms in cardiac cell therapy

Fig. 2

Repair pathways related to MSC-mediated therapeutic effects following ischemic injury. Autocrine pathways are involved in proliferation, survival and possible differentiation of MSCs. Paracrine pathways are elicited by secreted mediators that act in the vicinity of MSCs to promote angiogenesis, inhibit fibrosis and activate endogenous progenitor cells. Finally, endocrine-like pathways are induced when MSC (once remotely transplanted) are activated by distant injury and secreted trophic factors that circulate either in the vascular or lymphatic systems to induce pro-healing effects related to both autocrine and paracrine pathways