Human progenitor cells derived from cardiac adipose tissue ameliorate myocardial infarction in rodents.
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 30days 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.
Bayes-Genis
Antoni
A
Laboratory of Cell Physiology, Department of Cardiology, Hospital de la Santa Creu i Sant Pau, ICCC, Barcelona, Spain. abayes.germanstrias@gencat.cat
Soler-Botija
Carolina
C
Farré
Jordi
J
Sepúlveda
Pilar
P
Raya
Angel
A
Roura
Santiago
S
Prat-Vidal
Cristina
C
Gálvez-Montón
Carolina
C
Montero
José Anastasio
JA
Büscher
Dirk
D
Izpisúa Belmonte
Juan Carlos
JC
D000273:Adipose Tissue / Q000166:cytology*; D000368:Aged; D043925:Angiogenesis Inducing Agents / Q000378:metabolism; D000818:Animals; D002196:Capillaries / Q000473:pathology; D002454:Cell Differentiation; D019070:Cell Lineage; D002469:Cell Separation; D002478:Cells, Cultured; D018920:Coculture Techniques; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D006334:Heart Function Tests; D006801:Humans; D051379:Mice; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000473:pathology / Q000628:therapy*; D009206:Myocardium / Q000166:cytology*; D018919:Neovascularization, Physiologic; D051381:Rats; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology*; D014463:Ultrasonography
D043925:Angiogenesis Inducing Agents