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

Research output: Contribution to journalArticle

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

Fingerprint

1-Phosphatidylinositol 4-Kinase
Phosphatidylinositols
Stem cells
Mesenchymal Stromal Cells
Phosphatidylinositol 3-Kinases
Cell Survival
Myocardium
Phosphotransferases
Cells
Regeneration
Transplantation
Phosphorylation
Catheters
In Situ Nick-End Labeling
Stem Cell Transplantation
Cell- and Tissue-Based Therapy
Microvessels
Rats
Fibrosis
Down-Regulation

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Eun, Lucy Youngmin ; Song, Byeong Wook ; Cha, Min Ji ; Song, Heesang ; Kim, Il Kwon ; Choi, Eunmi ; Chang, Woochul ; Lim, Soyeon ; Choi, Eun Ju ; Ham, Onju ; Lee, Se Yeon ; Byun, Ki Hyun ; Jang, Yangsoo ; Hwang, Ki Chul. / Overexpression of phosphoinositide-3-kinase class II alpha enhances mesenchymal stem cell survival in infarcted myocardium. In: Biochemical and Biophysical Research Communications. 2010 ; Vol. 402, No. 2. pp. 272-279.
@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}",
year = "2010",
month = "11",
day = "12",
doi = "10.1016/j.bbrc.2010.10.013",
language = "English",
volume = "402",
pages = "272--279",
journal = "Biochemical and Biophysical Research Communications",
issn = "0006-291X",
publisher = "Academic Press Inc.",
number = "2",

}

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

Overexpression of phosphoinositide-3-kinase class II alpha enhances mesenchymal stem cell survival in infarcted myocardium. / Eun, Lucy Youngmin; Song, Byeong Wook; Cha, Min Ji; Song, Heesang; Kim, Il Kwon; Choi, Eunmi; Chang, Woochul; Lim, Soyeon; Choi, Eun Ju; Ham, Onju; Lee, Se Yeon; Byun, Ki Hyun; Jang, Yangsoo; Hwang, Ki Chul.

In: Biochemical and Biophysical Research Communications, Vol. 402, No. 2, 12.11.2010, p. 272-279.

Research output: Contribution to journalArticle

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

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.

UR - http://www.scopus.com/inward/record.url?scp=78149470891&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78149470891&partnerID=8YFLogxK

U2 - 10.1016/j.bbrc.2010.10.013

DO - 10.1016/j.bbrc.2010.10.013

M3 - Article

C2 - 20937252

AN - SCOPUS:78149470891

VL - 402

SP - 272

EP - 279

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

SN - 0006-291X

IS - 2

ER -