Skip to main content

Genetic modification of mesenchymal stem cells overexpressing CCR1 increases cell viability, migration, engraftment, and capillary density in the injured myocardium.

Publication ,  Journal Article
Huang, J; Zhang, Z; Guo, J; Ni, A; Deb, A; Zhang, L; Mirotsou, M; Pratt, RE; Dzau, VJ
Published in: Circ Res
June 11, 2010

RATIONALE: Although mesenchymal stem cell (MSC) transplantation has been shown to promote cardiac repair in acute myocardial injury in vivo, its overall restorative capacity appears to be restricted mainly because of poor cell viability and low engraftment in the ischemic myocardium. Specific chemokines are upregulated in the infarcted myocardium. However the expression levels of the corresponding chemokine receptors (eg, CCR1, CXCR2) in MSCs are very low. We hypothesized that this discordance may account for the poor MSC engraftment and survival. OBJECTIVE: To determine whether overexpression of CCR1 or CXCR2 chemokine receptors in MSCs augments their cell survival, migration and engraftment after injection in the infarcted myocardium. METHODS AND RESULTS: Overexpression of CCR1, but not CXCR2, dramatically increased chemokine-induced murine MSC migration and protected MSC from apoptosis in vitro. Moreover, when MSCs were injected intramyocardially one hour after coronary artery ligation, CCR1-MSCs accumulated in the infarcted myocardium at significantly higher levels than control-MSCs or CXCR2-MSCs 3 days postmyocardial infarction (MI). CCR1-MSC-injected hearts exhibited a significant reduction in infarct size, reduced cardiomyocytes apoptosis and increased capillary density in injured myocardium 3 days after MI. Furthermore, intramyocardial injection of CCR1-MSCs prevented cardiac remodeling and restored cardiac function 4 weeks after MI. CONCLUSIONS: Our results demonstrate the in vitro and in vivo salutary effects of genetic modification of stem cells. Specifically, overexpression of chemokine receptor enhances the migration, survival and engraftment of MSCs, and may provide a new therapeutic strategy for the injured myocardium.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Circ Res

DOI

EISSN

1524-4571

Publication Date

June 11, 2010

Volume

106

Issue

11

Start / End Page

1753 / 1762

Location

United States

Related Subject Headings

  • Ventricular Remodeling
  • Ventricular Function, Left
  • Transduction, Genetic
  • Time Factors
  • Regeneration
  • Recovery of Function
  • Receptors, Interleukin-8B
  • Receptors, CCR1
  • RNA Interference
  • Neovascularization, Physiologic
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Huang, J., Zhang, Z., Guo, J., Ni, A., Deb, A., Zhang, L., … Dzau, V. J. (2010). Genetic modification of mesenchymal stem cells overexpressing CCR1 increases cell viability, migration, engraftment, and capillary density in the injured myocardium. Circ Res, 106(11), 1753–1762. https://doi.org/10.1161/CIRCRESAHA.109.196030
Huang, Jing, Zhiping Zhang, Jian Guo, Aiguo Ni, Arjun Deb, Lunan Zhang, Maria Mirotsou, Richard E. Pratt, and Victor J. Dzau. “Genetic modification of mesenchymal stem cells overexpressing CCR1 increases cell viability, migration, engraftment, and capillary density in the injured myocardium.Circ Res 106, no. 11 (June 11, 2010): 1753–62. https://doi.org/10.1161/CIRCRESAHA.109.196030.
Huang, Jing, et al. “Genetic modification of mesenchymal stem cells overexpressing CCR1 increases cell viability, migration, engraftment, and capillary density in the injured myocardium.Circ Res, vol. 106, no. 11, June 2010, pp. 1753–62. Pubmed, doi:10.1161/CIRCRESAHA.109.196030.
Huang J, Zhang Z, Guo J, Ni A, Deb A, Zhang L, Mirotsou M, Pratt RE, Dzau VJ. Genetic modification of mesenchymal stem cells overexpressing CCR1 increases cell viability, migration, engraftment, and capillary density in the injured myocardium. Circ Res. 2010 Jun 11;106(11):1753–1762.

Published In

Circ Res

DOI

EISSN

1524-4571

Publication Date

June 11, 2010

Volume

106

Issue

11

Start / End Page

1753 / 1762

Location

United States

Related Subject Headings

  • Ventricular Remodeling
  • Ventricular Function, Left
  • Transduction, Genetic
  • Time Factors
  • Regeneration
  • Recovery of Function
  • Receptors, Interleukin-8B
  • Receptors, CCR1
  • RNA Interference
  • Neovascularization, Physiologic