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In Vitro Differentiation of Human Mesenchymal Stem Cells into Functional Cardiomyocyte-like Cells
Published on: August 9, 2017
Conditioned medium from human amniotic mesenchymal stromal cells limits infarct size and enhances angiogenesis
Patrizia Danieli1, Giuseppe Malpasso1, Maria Chiara Ciuffreda1
1Department of Cardiothoracic and Vascular Sciences, Coronary Care Unit and Laboratory of Clinical and Experimental Cardiology, Laboratory of Experimental Cardiology for Cell and Molecular Therapy, Division of Clinical Immunology, Immunohematology, and Transfusion Service, Center for the Study and Cure of Myelofibrosis, Biotechnology Research Laboratories, and Division of Obstetrics and Gynecology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy; Department of Molecular Medicine, Unit of Cardiology, University of Pavia, Pavia, Italy; Laboratory of Cardiovascular Genetics, IRCCS Istituto Auxologico Italiano, Milan, Italy; Department of Cardiology, University Medical Center Groningen, Groningen, The Netherlands; Department of Medicine, University of Cape Town, Cape Town, South Africa.
Abstract:
The paracrine properties of human amniotic membrane-derived mesenchymal stromal cells (hAMCs) have not been fully elucidated. The goal of the present study was to elucidate whether hAMCs can exert beneficial paracrine effects on infarcted rat hearts, in particular through cardioprotection and angiogenesis. Moreover, we aimed to identify the putative active paracrine mediators. hAMCs were isolated, expanded, and characterized. In vitro, conditioned medium from hAMC (hAMC-CM) exhibited cytoprotective and proangiogenic properties. In vivo, injection of hAMC-CM into infarcted rat hearts limited the infarct size, reduced cardiomyocyte apoptosis and ventricular remodeling, and strongly promoted capillary formation at the infarct border zone. Gene array analysis led to the identification of 32 genes encoding for the secreted factors overexpressed by hAMCs. Among these, midkine and secreted protein acidic and rich in cysteine were also upregulated at the protein level. Furthermore, high amounts of several proangiogenic factors were detected in hAMC-CM by cytokine array. Our results strongly support the concept that the administration of hAMC-CM favors the repair process after acute myocardial infarction.

