Human umbilical cord tissue-derived mesenchymal stromal cells attenuate remodeling after myocardial infarction by proangiogenic, antiapoptotic, and endogenous cell-activation mechanisms

• Type: Article in International Scientific Journal
• Date: 2014

Authors

Nascimento, DS (Author) ICBAS; Mosqueira, D (Author) Other; Sousa, LM (Author) Other; Teixeira, M (Author) Other; Filipe, M (Author) Other; Resende, TP (Author) Other; Araujo, AF (Author) Other; Valente, M (Author) Other; Almeida, J (Author) Other; Martins, JP (Author) Other; Santos, JM (Author) Other; Barcia, RN (Author) Other; Cruz, P (Author) Other; Cruz, H (Author) Other; Perpetua Pinto do O (Author) ICBAS

Journal

Title: Stem Cell Research & Therapy

Vol. 5

Final page: 5

ISSN: 1757-6512

Publisher: Palgrave Macmillan

Indexing

ISI Web of Knowledge - 82 Citations

Scopus - 103 Citations

Other information

Authenticus ID: P-009-6K5

DOI: 10.1186/scrt394

Abstract (EN): Introduction: Among 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. Methods: Human umbilical cord tissue-derived MSCs (UCX (R)), 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 (R) preconditioned under normoxia (CM) or hypoxia (CMH) was collected for subsequent in vitro assays. Results: Evaluation of the effects upon intramyocardial transplantation shows that UCX (R) preserved cardiac function and attenuated cardiac remodeling subsequent to myocardial infarction (MI). UCX (R) further led to increased capillary density and decreased apoptosis in the injured tissue. In vitro, UCX (R)-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. Conclusions: UCX (R) preserve cardiac function after intramyocardial transplantation in a MI murine model. The cardioprotective effects of UCX (R) 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 (R) should be considered an alternative cell source when designing new therapeutic approaches to treat MI.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 14