Haider KH, Aziz S (2017) Paracrine Hypothesis and Cardiac Repair Int J Stem Cell Res Transplant. 5(1), 265-267. 265 OPEN ACCESS http://scidoc.org/IJST.php Paracrine Hypothesis and Cardiac Repair Commentary Haider KH 1* , Aziz S 2 1 Department of Basic Sciences, Sulaiman AlRajhi Colleges, Kingdom of Saudi Arabia. 2 George Washington University, M Street NW, Suite, Washington DC, USA. International Journal of Stem Cell Research and Transplantation (IJST) ISSN: 2328-3548 *Corresponding Author: Khawaja Husnain Haider, PhD, Professor, Molecular and Cellular Pharmacology (Stem cells and Gene Therapy), Department of Basic Sciences, Sulaiman AlRajhi Colleges, P.O. Box 777, Al Bukairiyah-51941, Kingdom of Saudi Arabia. Tel: 06-3355555 Ext. -7704 Email: kh.haider@sr.edu.sa Received: May 08, 2017 Published: May 12, 2017 Citation: Haider KH, Aziz S (2017) Paracrine Hypothesis and Cardiac Repair. Int J Stem Cell Res Transplant. 5(1), 265-267. doi: http://dx.doi.org/10.19070/2328-3548-1700040 Copyright: Haider KH © 2017. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution and reproduction in any medium, provided the original author and source are credited. Commentary Last two decades of research has seen the emergence and pro- gress of stem cells from a myth to reality and their expediency in the clinical perspective as an effective therapeutic modality. De- spite immense progress and promising results from experimental animal studies and clinical trials, the provocative underlying mech- anism of their functional eficacy has led to diverging opinions and indulging the researchers into a continuous discussion. With controversies clouding the potential of stem cells to adopt mor- pho functionally competent cardiac phenotype, paracrine activity of the transplanted stem cells has been put forth as an alternative mechanism associated with the beneicial outcome of cell therapy. Although unique paracrine activity of a cell, besides endocrine activity and juxtacrine activity, constitutes an integral part of the cell-to-cell communication, the release of trophic factors from the transplanted cells favorably modulates the local microenvi- ronment in the cell transplanted region in the infarcted heart and positively impact the integration and reparability of the cell graft. Besides, the donor cells via their paracrine activity provide a con- ducive microenvironment for the host cardiac cells and enhance their survival via initiation of survival signaling. Additionally, the paracrine trophic factors create a chemical gradient to promote extravasation of bone marrow derived stem/progenitor cells into peripheral circulation for ultimate homing-in to the injured myo- cardium along with the resident cardiac stem cells to participate in the repair process. The use of paracrine factor-rich conditioned medium has also been used as an adjunct to cell therapy to en- hance the engraftment of the donor cells in the heart [1]. Despite wide acceptance of the paracrine hypothesis and publication of a plethora of studies that depict the release of a wide-array of trophic factors by various stem/progenitor cells including the bone marrow derived mesenchymal stem cells (MSCs), there is no single study published as yet that comprehensively proiles their paracrine activity. The secretome is cell-type dependent and is unique for each cell type under a given set of its culture condi- tions. For example, the composition of secretome of bone mar- row derived MSCs cultured under hypoxic conditions varies with the level of oxygen [2]. Besides being afluent in growth factors and cytokines, recent studies have reported the shedding of ex- osomes as part of their paracrine activity [3]. Exosomes are extra- cellular vesicles of endocytic origin and with less than 100 nm di- ameter and enriched in proteins and microRNAs [4]. Microarray proiling of the exosomes for their contents showed that MSCs use exosomes as carriers to deliver a distinct array of microRNAs to the neighboring cells as part of their mircine activity under giv- en set of conditions [5, 6]. Transplantation of MSCs or injection- based delivery of their derivative exosomes help in transfer of the microRNAs many of which have signiicant role in physiological functioning of cardiomyocytes at molecular and cellular levels as well as in the repair of the infarcted myocardium [7]. An important step forward in the exploitation of paracrine hy- pothesis is the cell-free therapeutic interventional approach wherein conditioned medium in toto or its fractionated compo- nents such as growth factors and exosomes from the bone mar- row derived progenitor cells is used to treat the ischemic heart. The importance of the cell-free therapy is to exploit the trophic Keywords: Cytokine; Heart; IL-6; Infarction; Mesenchymal Stem Cells; TGF-β; TNF-α. Abbreviations: CRP = C-Reactive Protein; HUVEC = Human Umbilical Vein Endothelial Cells; IL-6 = Interleukin-6; Mesenchymal Stem Cells = MSCs; TGF-β = Transforming Growth Factor-Beta; TNF-α = Tumor Necrosis Factor - Alpha.