This Article Full Text Full Text (PDF) All Versions of this Article: 120/5/408    most recent CIRCULATIONAHA.109.865154v2 CIRCULATIONAHA.109.865154v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Google Scholar Articles by Nelson, T. J. Articles by Terzic, A. PubMed PubMed Citation Articles by Nelson, T. J. Articles by Terzic, A. Pubmed/NCBI databases Medline Plus Health Information Heart Attack Related Collections Animal models of human disease Developmental biology Transplantation Other Treatment CV surgery: transplantation, ventricular assistance, cardiomyopathy CV surgery: other Acute myocardial infarction Related Article

(Circulation. 2009;120:408-416.)
© 2009 American Heart Association, Inc.

Molecular Cardiology

Repair of Acute Myocardial Infarction by Human Stemness Factors Induced Pluripotent Stem Cells

Timothy J. Nelson, MD, PhD; Almudena Martinez-Fernandez, PharmD; Satsuki Yamada, MD, PhD; Carmen Perez-Terzic, MD, PhD; Yasuhiro Ikeda, DVM, PhD; Andre Terzic, MD, PhD

From the Division of Cardiovascular Diseases, Departments of Medicine, Molecular Pharmacology and Experimental Therapeutics, and Medical Genetics (T.J.N., A.M.-F., S.Y., C.P.-T., A.T.); Physical Medicine and Rehabilitation (C.P.-T.); and Molecular Medicine (Y.I.), Mayo Clinic, Rochester, Minn.

Correspondence to Andre Terzic, MD, PhD, Mayo Clinic, 200 First St SW, Rochester, MN 55905. E-mail terzic.andre{at}mayo.edu

Received March 13, 2009; accepted June 1, 2009.

Background— Nuclear reprogramming provides an emerging strategy to produce embryo-independent pluripotent stem cells from somatic tissue. Induced pluripotent stem cells (iPS) demonstrate aptitude for de novo cardiac differentiation, yet their potential for heart disease therapy has not been tested.

Methods and Results— In this study, fibroblasts transduced with human stemness factors OCT3/4, SOX2, KLF4, and c-MYC converted into an embryonic stem cell–like phenotype and demonstrated the ability to spontaneously assimilate into preimplantation host morula via diploid aggregation, unique to bona fide pluripotent cells. In utero, iPS-derived chimera executed differentiation programs to construct normal heart parenchyma patterning. Within infarcted hearts in the adult, intramyocardial delivery of iPS yielded progeny that properly engrafted without disrupting cytoarchitecture in immunocompetent recipients. In contrast to parental nonreparative fibroblasts, iPS treatment restored postischemic contractile performance, ventricular wall thickness, and electric stability while achieving in situ regeneration of cardiac, smooth muscle, and endothelial tissue.

Conclusions— Fibroblasts reprogrammed by human stemness factors thus acquire the potential to repair acute myocardial infarction, establishing iPS in the treatment of heart disease.

---

 

CLINICAL PERSPECTIVE

Related Article:

Clinical Summaries
Circulation 2009 120: 355-356. [Extract] [Full Text]

This article has been cited by other articles:

				K. Schenke-Layland and W. R. MacLellan Induced Pluripotent Stem Cells: It's Like Deja Vu All Over Again Circulation, October 13, 2009; 120(15): 1462 - 1464. [Full Text] [PDF]

				B. J. Gersh, R. D. Simari, A. Behfar, C. M. Terzic, and A. Terzic Cardiac Cell Repair Therapy: A Clinical Perspective Mayo Clin. Proc., October 1, 2009; 84(10): 876 - 892. [Abstract] [Full Text] [PDF]

				T. J. Kamp and G. E. Lyons On the Road to iPS Cell Cardiovascular Applications Circ. Res., September 25, 2009; 105(7): 617 - 619. [Full Text] [PDF]

				A. Martinez-Fernandez, T. J. Nelson, S. Yamada, S. Reyes, A. E. Alekseev, C. Perez-Terzic, Y. Ikeda, and A. Terzic iPS Programmed Without c-MYC Yield Proficient Cardiogenesis for Functional Heart Chimerism Circ. Res., September 25, 2009; 105(7): 648 - 656. [Abstract] [Full Text] [PDF]