Overexpression of phosphoinositide-3-kinase class II alpha enhances mesenchymal stem cell survival in infarcted myocardium

Lucy Youngmin Eun, Byeong Wook Song, Min Ji Cha, Heesang Song, Il Kwon Kim, Eunmi Choi, Woochul Chang, Soyeon Lim, Eun Ju Choi, Onju Ham, Se Yeon Lee, Ki Hyun Byun, Yangsoo Jang, Ki Chul Hwang

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Abstract

The efficacy of mesenchymal stem cell (MSC) therapy for myocardial regeneration is limited by the poor survival of stem cells after transplantation into the infarcted heart. To improve the cell survival of MSCs in the infarcted heart, MSCs were genetically engineered to overexpress phosphoinositide-3-kinase class II alpha (PI3K-C2α). PI3K-C2α overexpression increased PI3K expression and the cell viability of MSCs. Furthermore, levels of survival-related phosphorylation were elevated in PI3K-C2α-MSCs. But, the level of apoptotic proteins downregulated and the number of PI-positive cells decreased in PI3K-C2α-MSCs compared to hypoxic MSCs. Nine rats per group had 1×106 cells (20μl PBS) transplanted after myocardial infarction. One week after transplantation, infarct size and area of fibrosis were reduced in the PI3K-C2α-MSC-transplanted group. The number of TUNEL positive cells declined, while the mean microvessel count per field was higher in the PI3K-C2α-MSC group than the MSC-injected group. Heart function was improved in the PI3K-C2α-MSCs group as assessed using a Millar catheter at 3weeks after transplantation. These findings suggest that overexpression of PI3K-C2α in MSCs can assist cell survival and enhance myocardial regeneration.

Original languageEnglish
Pages (from-to)272-279
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume402
Issue number2
DOIs
Publication statusPublished - 2010 Nov 12

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All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Eun, L. Y., Song, B. W., Cha, M. J., Song, H., Kim, I. K., Choi, E., Chang, W., Lim, S., Choi, E. J., Ham, O., Lee, S. Y., Byun, K. H., Jang, Y., & Hwang, K. C. (2010). Overexpression of phosphoinositide-3-kinase class II alpha enhances mesenchymal stem cell survival in infarcted myocardium. Biochemical and Biophysical Research Communications, 402(2), 272-279. https://doi.org/10.1016/j.bbrc.2010.10.013