During the past several years, there has been intense research in the field of bone marrow-derived stem cell (BMSC) therapy to facilitate its translation into clinical setting. Although a lot has been accomplished, plenty of challenges lie ahead. Furthermore, there is a growing body of evidence showing that administration of BMSC-derived conditioned media (BMSC-CM) can recapitulate the beneficial effects observed after stem cell therapy. BMSCs produce a wide range of cytokines and chemokines that have, until now, shown extensive therapeutic potential. These paracrine mechanisms could be as diverse as stimulating receptor-mediated survival pathways, inducing stem cell homing and differentiation or regulating the anti-inflammatory effects in wounded areas. The current review reflects the rapid shift of interest from BMSC to BMSC-CM to alleviate many logistical and technical issues regarding cell therapy and evaluates its future potential as an effective regenerative therapy. 1. Introduction The objective of stem cell regenerative therapy is to treat damaged organ tissues by avoiding the processes of cell death and/or inadvertent remodeled Tissue [1]. Great optimism has resulted from bone marrow derived stem cell (BMSC) research ever since it showed to contribute significantly to the reestablishment of some functionality in injured organs [2, 3]. The mechanisms by which stem cells function and reverse the effects of cell death include differentiation, cell fusion, and secretion of cytokines or paracrine effects [1, 4–6]. More specifically, studies injecting BMSCs have shown to improve functionality of ischemic tissue by promoting neovascularization, inhibition of apoptosis and anti-inflammation, better localization and homing of therapeutic cells, and stimulation of endogenous cells differentiation and proliferation [7–10]. Although a lot of research has been focused on the ability of stem cells to differentiate within the injured areas, more recent research suggests other mechanisms may be more therapeutically relevant. It will be argued that understanding paracrine mechanisms, mediated by stem cells, is essential if stem cell regenerative therapy is ever to reach clinical importance. Indeed, understanding the therapeutic effects of regenerative therapy using BMSCs becomes more relevant when we look at the paracrine factors, which are secreted by BMSCs. For example, the frequency of stem cell engraftment and the number of newly generated cardiomyocytes or vascular cells are too insignificant to represent the remarkable cardiac functional improvement
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