Human progenitor cells derived from cardiac adipose tissue ameliorate myocardial infarction in rodents

• Published in: Journal of molecular and cellular cardiology Vol. 49; no. 5; pp. 771 - 780
• Main Authors: Bayes-Genis, Antoni, Soler-Botija, Carolina, Farré, Jordi, Sepúlveda, Pilar, Raya, Angel, Roura, Santiago, Prat-Vidal, Cristina, Gálvez-Montón, Carolina, Montero, José Anastasio, Büscher, Dirk, Belmonte, Juan Carlos Izpisúa
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-11-2010
• Subjects: Adipose Tissue - cytology; Aged; Angiogenesis Inducing Agents - metabolism; Animals; Capillaries - pathology; Cardiac adipose tissue; Cardiovascular; Cell Differentiation; Cell Lineage; Cell Separation; Cell transplantation; Cells, Cultured; Coculture Techniques; Endothelial Cells - cytology; Endothelial Cells - metabolism; Heart Function Tests; Humans; Mice; Myocardial infarction; Myocardial Infarction - diagnostic imaging; Myocardial Infarction - pathology; Myocardial Infarction - therapy; Myocardium - cytology; Neovascularization, Physiologic; Progenitor cells; Rats; Stem Cell Transplantation; Stem Cells - cytology; Ultrasonography; Myocardial infarction; Progenitor cells; Cell transplantation; Cardiac adipose tissue
• ISSN: 0022-2828; 1095-8584
• DOI: 10.1016/j.yjmcc.2010.08.010

Abstract Myocardial infarction caused by vascular occlusion results in the formation of nonfunctional fibrous tissue. Cumulative evidence indicates that cell therapy modestly improves cardiac function; thus, novel cell sources with the potential to repair injured tissue are actively sought. Here, we identify and characterize a cell population of cardiac adipose tissue-derived progenitor cells (ATDPCs) from biopsies of human adult cardiac adipose tissue. Cardiac ATDPCs express a mesenchymal stem cell-like marker profile (strongly positive for CD105, CD44, CD166, CD29 and CD90) and have immunosuppressive capacity. Moreover, cardiac ATDPCs have an inherent cardiac-like phenotype and were able to express de novo myocardial and endothelial markers in vitro but not to differentiate into adipocytes. In addition, when cardiac ATDPCs were transplanted into injured myocardium in mouse and rat models of myocardial infarction, the engrafted cells expressed cardiac (troponin I, sarcomeric α-actinin) and endothelial (CD31) markers, vascularization increased, and infarct size was reduced in mice and rats. Moreover, significant differences between control and cell-treated groups were found in fractional shortening and ejection fraction, and the anterior wall remained significantly thicker 30 days after cardiac delivery of ATDPCs. Finally, cardiac ATDPCs secreted proangiogenic factors under in vitro hypoxic conditions, suggesting a paracrine effect to promote local vascularization. Our results indicate that the population of progenitor cells isolated from human cardiac adipose tissue (cardiac ATDPCs) may be valid candidates for future use in cell therapy to regenerate injured myocardium.