Abstract
IntroductionAmong the plethora of cells under investigation to restore a functional myocardium, mesenchymal stromal cells (MSCs) have been granted considerable interest. However, whereas the beneficial effects of bone marrow MSCs (BM-MSCs) in the context of the diseased heart are widely reported, data are still scarce on MSCs from the umbilical cord matrix (UCM-MSCs). Herein we report on the effect of UCM-MSC transplantation to the infarcted murine heart, seconded by the dissection of the molecular mechanisms at play.MethodsHuman umbilical cord tissue-derived MSCs (UCX®), obtained by using a proprietary technology developed by ECBio, were delivered via intramyocardial injection to C57BL/6 females subjected to permanent ligation of the left descending coronary artery. Moreover, medium produced by cultured UCX® preconditioned under normoxia (CM) or hypoxia (CMH) was collected for subsequent in vitro assays.ResultsEvaluation of the effects upon intramyocardial transplantation shows that UCX® preserved cardiac function and attenuated cardiac remodeling subsequent to myocardial infarction (MI). UCX® further led to increased capillary density and decreased apoptosis in the injured tissue. In vitro, UCX®-conditioned medium displayed (a) proangiogenic activity by promoting the formation of capillary-like structures by human umbilical vein endothelial cells (HUVECs), and (b) antiapoptotic activity in HL-1 cardiomyocytes subjected to hypoxia. Moreover, in adult murine cardiac Sca-1+ progenitor cells (CPCs), conditioned medium enhanced mitogenic activity while activating a gene program characteristic of cardiomyogenic differentiation.ConclusionsUCX® preserve cardiac function after intramyocardial transplantation in a MI murine model. The cardioprotective effects of UCX® were attributed to paracrine mechanisms that appear to enhance angiogenesis, limit the extent of the apoptosis, augment proliferation, and activate a pool of resident CPCs. Overall, these results suggest that UCX® should be considered an alternative cell source when designing new therapeutic approaches to treat MI.
Highlights
Among the plethora of cells under investigation to restore a functional myocardium, mesenchymal stromal cells (MSCs) have been granted considerable interest
We recently showed that UCX® were more potent modulators of the immune system than bone marrow-derived MSCs (BM-MSCs), being able to repress T-cell activation and promote the expansion of regulatory T cells more efficiently [13]
Intramyocardial transplantation of UCX® preserves cardiac performance and attenuates adverse left ventricle (LV) remodeling 2 weeks after Myocardial infarction (MI) UCX® were isolated by using a proprietary method (PCT/IB2008/054067) that yields a well-defined number of cells by using a precise proportion between tissuedigestion enzyme activity units, tissue mass, digestion solution volume, and void volume
Summary
Among the plethora of cells under investigation to restore a functional myocardium, mesenchymal stromal cells (MSCs) have been granted considerable interest. Whereas the beneficial effects of bone marrow MSCs (BM-MSCs) in the context of the diseased heart are widely reported, data are still scarce on MSCs from the umbilical cord matrix (UCM-MSCs). We report on the effect of UCM-MSC transplantation to the infarcted murine heart, seconded by the dissection of the molecular mechanisms at play. Myocardial infarction (MI) is characterized by extensive cardiomyocyte death and functional degradation of the cardiac tissue downstream from a coronary occlusion. A cascade of dramatic biochemical and morphologic events, collectively designated cardiac remodeling, is initiated. These events culminate in the formation of a nonfunctional scar in place of the damaged myocardium. Cell therapies aimed at directing heart’s response toward a more-efficient repair and/or myocardial regeneration have received considerable attention in the last decade [3]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
