The DOI matches its Crossref record; 34 of the 34 references it cites were found in a registry or an index.
IGF-1–Overexpressing Mesenchymal Stem Cells Accelerate Bone Marrow Stem Cell Mobilization via Paracrine Activation of SDF-1α/CXCR4 Signaling to Promote Myocardial Repair
Abstract
We hypothesized that mesenchymal stem cells (MSCs) overexpressing insulin-like growth factor (IGF)-1 showed improved survival and engraftment in the infarcted heart and promoted stem cell recruitment through paracrine release of stromal cell–derived factor (SDF)-1α. Rat bone marrow–derived MSCs were used as nontransduced ( Norm MSCs) or transduced with adenoviral-null vector ( Null MSCs) or vector encoding for IGF-1 ( IGF-1 MSCs). IGF-1 MSCs secreted higher IGF-1 until 12 days of observation ( P <0.001 versus Null MSCs). Molecular studies revealed activation of phosphoinositide 3-kinase, Akt, and Bcl.xL and inhibition of glycogen synthase kinase 3β besides release of SDF-1α in parallel with IGF-1 expression in IGF-1 MSCs. For in vivo studies, 70 μL of DMEM without cells (group 1) or containing 1.5×10 6 Null MSCs (group 2) or IGF-1 MSCs (group 3) were implanted intramyocardially in a female rat model of permanent coronary artery occlusion. One week later, immunoblot on rat heart tissue (n=4 per group) showed elevated myocardial IGF-1 and phospho-Akt in group 3 and higher survival of IGF-1 MSCs ( P <0.06 versus Null MSCs) (n=6 per group). SDF-1α was increased in group 3 animal hearts (20-fold versus group 2), with massive mobilization and homing of ckit + , MDR1 + , CD31 + , and CD34 + cells into the infarcted heart. Infarction size was significantly reduced in cell transplanted groups compared with the control. Confocal imaging after immunostaining for myosin heavy chain, actinin, connexin-43, and von Willebrand factor VIII showed extensive angiomyogenesis in the infarcted heart. Indices of left ventricular function, including ejection fraction and fractional shortening, were improved in group 3 as compared with group 1 ( P <0.05). In conclusion, the strategy of IGF-1 transgene expression induced massive stem cell mobilization via SDF-1α signaling and culminated in extensive angiomyogenesis in the infarcted heart.
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Cardiac Stem Cell and Myocyte Aging, Heart Failure, and Insulin-Like Growth Factor-1 Overexpression
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Mesenchymal stem cells and immunomodulation: current status and future prospects
Gao, F., Chiu, S. M., Motan, D. A. L., Zhang, Z., Chen, L., Ji, H.-L., Tse, H.-F., Fu, Q.-L., & Lian, Q. (2016) · Cell Death & Disease · doi:10.1038/cddis.2015.327 · Cited by 1,121
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Genetic Engineering of Mesenchymal Stem Cells and Its Application in Human Disease Therapy
Hodgkinson, C. P., Gomez, J. A., Mirotsou, M., & Dzau, V. J. (2010) · Human Gene Therapy · doi:10.1089/hum.2010.165 · Cited by 150
Park, B.-W., Jung, S.-H., Das, S., Lee, S. M., Park, J.-H., Kim, H., Hwang, J.-W., Lee, S., Kim, H.-J., Kim, H.-Y., et al. (2020) · Science Advances · doi:10.1126/sciadv.aay6994 · Cited by 133
Metadata
- Authors
- Haider, H. K., Jiang, S., Idris, N. M., & Ashraf, M.
- Venue
- Circulation Research
- Published
- 2008-11-21
- Volume
- 103
- Issue
- 11
- Pages
- 1300-1308
- ISSN
- 0009-7330 (ISSN-L)
- 1524-4571
- OpenAlex
- W2041360667
- Cited by
- 422
- References
- 34
- FWCI
- 13.15
- Type
- journal article
- Language
- en
- Open access
- closed
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- CoChat. (2026). Citation check: IGF-1–Overexpressing Mesenchymal Stem Cells Accelerate Bone Marrow Stem Cell Mobilization via Paracrine Activation of SDF-1α/CXCR4 Signaling to Promote Myocardial Repair. https://app.cochat.ai/papers/10.1161/circresaha.108.186742
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- Haider, H. K., Jiang, S., Idris, N. M., & Ashraf, M. (2008). IGF-1–Overexpressing Mesenchymal Stem Cells Accelerate Bone Marrow Stem Cell Mobilization via Paracrine Activation of SDF-1α/CXCR4 Signaling to Promote Myocardial Repair. Circulation Research. https://doi.org/10.1161/circresaha.108.186742
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