TY - JOUR
T1 - Direct comparison of different stem cell types and subpopulations reveals superior paracrine potency and myocardial repair efficacy with cardiosphere-derived cells
AU - Li, Tao Sheng
AU - Cheng, Ke
AU - Malliaras, Konstantinos
AU - Smith, Rachel Ruckdeschel
AU - Zhang, Yiqiang
AU - Sun, Baiming
AU - Matsushita, Noriko
AU - Blusztajn, Agnieszka
AU - Terrovitis, John
AU - Kusuoka, Hideo
AU - Marbán, Linda
AU - Marbán, Eduardo
N1 - Funding Information:
This study was supported by the National Institutes of Health ( HL095203 ) to Capricor, Inc., by the National Institutes of Health ( U54 HL081028 ) to Dr. E. Marbán, and by the Cedars-Sinai Board of Governors Heart Stem Cell Center. Dr. E. Marbán is the Mark S. Siegel Family Professor of the Cedars-Sinai Medical Center. Dr. E. Marbán and Dr. L. Marbán hold founders' equity in Capricor, Inc. Drs. Smith, Blusztajn, Terrovitis, and L. Marbán are employed by Capricor, Inc. Drs. Malliaras and Terrovitis are consultants of Capricor, Inc.
PY - 2012/3/6
Y1 - 2012/3/6
N2 - Objectives: The goal of this study was to conduct a direct head-to-head comparison of different stem cell types in vitro for various assays of potency and in vivo for functional myocardial repair in the same mouse model of myocardial infarction. Background: Adult stem cells of diverse origins (e.g., bone marrow, fat, heart) and antigenic identity have been studied for repair of the damaged heart, but the relative utility of the various cell types remains unclear. Methods: Human cardiosphere-derived cells (CDCs), bone marrowderived mesenchymal stem cells, adipose tissuederived mesenchymal stem cells, and bone marrow mononuclear cells were compared. Results: CDCs revealed a distinctive phenotype with uniform expression of CD105, partial expression of c-kit and CD90, and negligible expression of hematopoietic markers. In vitro, CDCs showed the greatest myogenic differentiation potency, highest angiogenic potential, and relatively high production of various angiogenic and antiapoptotic-secreted factors. In vivo, injection of CDCs into the infarcted mouse hearts resulted in superior improvement of cardiac function, the highest cell engraftment and myogenic differentiation rates, and the least-abnormal heart morphology 3 weeks after treatment. CDC-treated hearts also exhibited the lowest number of apoptotic cells. The c-kit + subpopulation purified from CDCs produced lower levels of paracrine factors and inferior functional benefit when compared with unsorted CDCs. To validate the comparison of cells from various human donors, selected results were confirmed in cells of different types derived from individual rats. Conclusions: CDCs exhibited a balanced profile of paracrine factor production and, among various comparator cell types/subpopulations, provided the greatest functional benefit in experimental myocardial infarction.
AB - Objectives: The goal of this study was to conduct a direct head-to-head comparison of different stem cell types in vitro for various assays of potency and in vivo for functional myocardial repair in the same mouse model of myocardial infarction. Background: Adult stem cells of diverse origins (e.g., bone marrow, fat, heart) and antigenic identity have been studied for repair of the damaged heart, but the relative utility of the various cell types remains unclear. Methods: Human cardiosphere-derived cells (CDCs), bone marrowderived mesenchymal stem cells, adipose tissuederived mesenchymal stem cells, and bone marrow mononuclear cells were compared. Results: CDCs revealed a distinctive phenotype with uniform expression of CD105, partial expression of c-kit and CD90, and negligible expression of hematopoietic markers. In vitro, CDCs showed the greatest myogenic differentiation potency, highest angiogenic potential, and relatively high production of various angiogenic and antiapoptotic-secreted factors. In vivo, injection of CDCs into the infarcted mouse hearts resulted in superior improvement of cardiac function, the highest cell engraftment and myogenic differentiation rates, and the least-abnormal heart morphology 3 weeks after treatment. CDC-treated hearts also exhibited the lowest number of apoptotic cells. The c-kit + subpopulation purified from CDCs produced lower levels of paracrine factors and inferior functional benefit when compared with unsorted CDCs. To validate the comparison of cells from various human donors, selected results were confirmed in cells of different types derived from individual rats. Conclusions: CDCs exhibited a balanced profile of paracrine factor production and, among various comparator cell types/subpopulations, provided the greatest functional benefit in experimental myocardial infarction.
KW - cardiac stem cells
KW - mesenchymal stem cells
KW - myocardial regeneration
KW - paracrine effects
UR - http://www.scopus.com/inward/record.url?scp=84863230134&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84863230134&partnerID=8YFLogxK
U2 - 10.1016/j.jacc.2011.11.029
DO - 10.1016/j.jacc.2011.11.029
M3 - Article
C2 - 22381431
AN - SCOPUS:84863230134
SN - 0735-1097
VL - 59
SP - 942
EP - 953
JO - Journal of the American College of Cardiology
JF - Journal of the American College of Cardiology
IS - 10
ER -