Supportive interaction between cell survival signaling and angiocompetent factors enhances donor cell survival and promotes angiomyogenesis for cardiac repair

Shujia Jiang, Husnain Kh Haider, Niagara M. Idris, Asmat Salim, Muhammad Ashraf

Research output: Contribution to journalArticle

136 Citations (Scopus)

Abstract

Akt is a major cell survival and angiogenic mediator downstream of angiopoietin-1 (Ang-1)/Tie-2 signaling pathway. We hypothesize that transplantation of mesenchymal stem cells (MSCs) co-overexpressing Ang-1 and Akt lead to better prognosis. Ang-1 and Akt genes were adenovirally transduced into MSCs from male Fischer rats. Cytoprotective effects of transgene overexpression in vitro were assessed by exposure of cells to 8 hours of anoxia. TUNEL and measurement of lactate dehydrogenase showed that MSCs co-overexpressing Ang-1 and Akt (MAAs) were more resistant to anoxia as compared with the nontransduced MSCs or those transduced with Ang-1 or Akt alone. For in vivo studies, after permanent coronary artery occlusion, animals were grouped (n=20/group) to receive intramyocardial injections of 70 μL of basal medium without cells (group 1) or containing 3×10 nontransduced MSCs (group 2) or MAAs (group 3). Four animals per group were euthanized on 4, 7, and 14 days after cell transplantation for molecular studies. Extensive survival of MAAs was observed in group 3, which continued to co-overexpress transgenes in rat heart at 2 weeks after cell transplantation. Immunohistology at 4 weeks revealed myogenic differentiation of donor cells at the site of cell graft. Blood vessel density was highest in the infarct and periinfarct regions in group 3 (P<0.05). Echocardiography at 4 weeks showed that heart function indices were significantly improved in group 3 (P<0.05), including ejection fraction and fractional shortening as compared with groups 1 and 2. We conclude that supportive interaction between Ang-1 and Akt during MSC transplantation gave better prognosis via enhanced cell survival, improved angiomyogenesis, and restored global cardiac function.

Original languageEnglish (US)
Pages (from-to)776-784
Number of pages9
JournalCirculation research
Volume99
Issue number7
DOIs
StatePublished - Oct 1 2006
Externally publishedYes

Fingerprint

Angiopoietin-1
Cell Survival
Mesenchymal Stromal Cells
Mesenchymal Stem Cell Transplantation
Cell Transplantation
Transgenes
Coronary Occlusion
Inbred F344 Rats
In Situ Nick-End Labeling
L-Lactate Dehydrogenase
Blood Vessels
Echocardiography
Cell Differentiation
Coronary Vessels
Transplants
Injections
Genes

Keywords

  • Adult stem cells
  • Akt
  • Angiogenesis
  • Angiopoietin-1
  • Heart

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Supportive interaction between cell survival signaling and angiocompetent factors enhances donor cell survival and promotes angiomyogenesis for cardiac repair. / Jiang, Shujia; Haider, Husnain Kh; Idris, Niagara M.; Salim, Asmat; Ashraf, Muhammad.

In: Circulation research, Vol. 99, No. 7, 01.10.2006, p. 776-784.

Research output: Contribution to journalArticle

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