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

doi:10.1016/j.bbrc.2010.10.013

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

Department of Internal Medicine

Research output: Contribution to journal › Article › peer-review

26 Citations (Scopus)

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 language	English
Pages (from-to)	272-279
Number of pages	8
Journal	Biochemical and Biophysical Research Communications
Volume	402
Issue number	2
DOIs	https://doi.org/10.1016/j.bbrc.2010.10.013
Publication status	Published - 2010 Nov 12

Bibliographical note

Funding Information:
This research was supported by Korea Science and Engineering Foundation (KOSEF) grant funded by MOST ( M1064102000106N410200110 ), a grant ( SC-2150 ) from Stem Cell Research Center of 21st Century Frontier Research Program funded by the Ministry of Education, Science and Technology, Republic of Korea and by the Korea Science, and a grant from the Korea Health 21 R&D Project, Ministry of Health & Welfare, Republic of Korea ( A085136 ).

All Science Journal Classification (ASJC) codes

Biophysics
Biochemistry
Molecular Biology
Cell Biology

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10.1016/j.bbrc.2010.10.013

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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

@article{cda20ac53a68427ba1f44102df06a3c2,

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

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.",

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

note = "Funding Information: This research was supported by Korea Science and Engineering Foundation (KOSEF) grant funded by MOST ( M1064102000106N410200110 ), a grant ( SC-2150 ) from Stem Cell Research Center of 21st Century Frontier Research Program funded by the Ministry of Education, Science and Technology, Republic of Korea and by the Korea Science, and a grant from the Korea Health 21 R&D Project, Ministry of Health & Welfare, Republic of Korea ( A085136 ).",

year = "2010",

month = nov,

day = "12",

doi = "10.1016/j.bbrc.2010.10.013",

language = "English",

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Eun, LY, Song, BW, Cha, MJ, Song, H, Kim, IK, Choi, E, Chang, W, Lim, S, Choi, EJ, Ham, O, Lee, SY, Byun, KH, Jang, Y & Hwang, KC 2010, 'Overexpression of phosphoinositide-3-kinase class II alpha enhances mesenchymal stem cell survival in infarcted myocardium', Biochemical and Biophysical Research Communications, vol. 402, no. 2, pp. 272-279. https://doi.org/10.1016/j.bbrc.2010.10.013

TY - JOUR

T1 - Overexpression of phosphoinositide-3-kinase class II alpha enhances mesenchymal stem cell survival in infarcted myocardium

AU - Eun, Lucy Youngmin

AU - Song, Byeong Wook

AU - Cha, Min Ji

AU - Song, Heesang

AU - Kim, Il Kwon

AU - Choi, Eunmi

AU - Chang, Woochul

AU - Lim, Soyeon

AU - Choi, Eun Ju

AU - Ham, Onju

AU - Lee, Se Yeon

AU - Byun, Ki Hyun

AU - Jang, Yangsoo

AU - Hwang, Ki Chul

N1 - Funding Information: This research was supported by Korea Science and Engineering Foundation (KOSEF) grant funded by MOST ( M1064102000106N410200110 ), a grant ( SC-2150 ) from Stem Cell Research Center of 21st Century Frontier Research Program funded by the Ministry of Education, Science and Technology, Republic of Korea and by the Korea Science, and a grant from the Korea Health 21 R&D Project, Ministry of Health & Welfare, Republic of Korea ( A085136 ).

PY - 2010/11/12

Y1 - 2010/11/12

N2 - 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.

AB - 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.

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JO - Biochemical and Biophysical Research Communications

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

Abstract

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