Cardiac progenitors derived from reprogrammed mesenchymal stem cells contribute to angiomyogenic repair of the infarcted heart

Stephanie Buccini, Khawaja Husnain Haider, Rafeeq P.H. Ahmed, Shujia Jiang, Muhammad Ashraf

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

The strategy to reprogram somatic stem cells to pluripotency status has provided an alternative source of surrogate ES cells (ESC). We report efficient reprogramming of multipotent bone marrow (BM) mesenchymal stem cells (MSC) to pluripotent status and the resultant MSC derived iPS cells (MiPS) and their derived progenitors effectively repaired the infarcted heart. MSC from young, male, Oct4-GFP transgenic mice were reprogrammed by retroviral transduction with Oct4, Sox2, Klf4, and c-Myc stemness factors. MiPS thus generated displayed characteristics of mouse ESC including morphology, surface antigens, gene and miR expression profiles. MiPS also formed spontaneously beating cardiac progenitors which expressed cardiac specific transcription factors and protein markers including Gata4, Mef2c, Nkx2.5, myosin heavy chain, troponin-I, and troponin-T, and showed ultra structural characteristics typical of cardiomyocytes. Intramyocardial delivery of MiPS (group-2) and their derivative cardiac-like cells (MiPS-CP; group-3) in a mouse model of acute myocardial infarction showed extensive survival and engraftment at 4 weeks with resultant attenuation of infarct size (p<0.001 vs. DMEM injected control; n = 4). Engraftment of MiPS-CP was without cardiac tumorigenesis as compared to 21 % in MiPS transplanted animals. Furthermore, angiogenesis was improved in groups-2 and 3 (p<0.001 vs. control). Transthoracic echocardiography revealed significantly preserved indices of cardiac contractility (ejection fraction p<0.001 and fractional shortening p<0.001 vs. control; n = 7). MSC were successfully reprogrammed into MiPS that displayed ESC-like characteristics and differentiated into spontaneously beating cardiomyocytes. Cardiac progenitors derived from MiPS repopulated the infarcted heart without tumorigenesis and improved global cardiac function.

Original languageEnglish (US)
Article number301
JournalBasic Research in Cardiology
Volume107
Issue number6
DOIs
StatePublished - Oct 18 2012

Fingerprint

Mesenchymal Stromal Cells
Cardiac Myocytes
Carcinogenesis
Troponin T
Adult Stem Cells
Troponin I
Myosin Heavy Chains
Surface Antigens
Transcriptome
Transgenic Mice
Echocardiography
Transcription Factors
Bone Marrow
Myocardial Infarction

Keywords

  • Bone marrow
  • Heart
  • Mesenchymal
  • Pluripotency
  • Reprogramming
  • iPS cells

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Cardiac progenitors derived from reprogrammed mesenchymal stem cells contribute to angiomyogenic repair of the infarcted heart. / Buccini, Stephanie; Haider, Khawaja Husnain; Ahmed, Rafeeq P.H.; Jiang, Shujia; Ashraf, Muhammad.

In: Basic Research in Cardiology, Vol. 107, No. 6, 301, 18.10.2012.

Research output: Contribution to journalArticle

Buccini, Stephanie ; Haider, Khawaja Husnain ; Ahmed, Rafeeq P.H. ; Jiang, Shujia ; Ashraf, Muhammad. / Cardiac progenitors derived from reprogrammed mesenchymal stem cells contribute to angiomyogenic repair of the infarcted heart. In: Basic Research in Cardiology. 2012 ; Vol. 107, No. 6.
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