The effects of mesenchymal stem cells transduced with Akt in a porcine myocardial infarction model

Sang Yup Lim; Yong Sook Kim; Youngkeun Ahn; Myung Ho Jeong; Moon Hwa Hong; Soo Yeon Joo; Kwang Il Nam; Jeong Gwan Cho; Peter M. Kang; Jong Chun Park

doi:10.1016/j.cardiores.2006.02.016

The effects of mesenchymal stem cells transduced with Akt in a porcine myocardial infarction model

Sang Yup Lim, Yong Sook Kim, Youngkeun Ahn, Myung Ho Jeong, Moon Hwa Hong, Soo Yeon Joo, Kwang Il Nam, Jeong Gwan Cho, Peter M. Kang, Jong Chun Park

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

151 Citations (Scopus)

Abstract

Objective: This study was designed to examine whether mesenchymal stem cells (MSCs) transduced with Akt enhance cardiac repair after transplantation into the ischemic porcine heart. Methods: MSCs isolated from porcine bone marrow and transduced with myr-Akt were transplanted into porcine hearts after experimental myocardial infarction (MI) using intracoronary injection [Group I, vehicle; Group II, MSCs; Group III, Akt-MSCs]. Myocardial single photon emission tomography (M-SPECT) was performed to assess myocardial function and the infarcted area. Pigs were also sacrificed for immunohistochemical characterization and histologic analysis. In addition, in vitro assays were performed to examine the resistance of Akt-MSCs to H₂O₂ stimulation. Results: Transplantation of MSCs into the ischemic porcine myocardium (Group II) increased the left ventricular ejection fraction (ΔLV EF; - 6.3 ± 15.1% versus 0.5 ± 6.4%, P < 0.001) and decreased the Δarea of MI (6.8 ± 5.6% versus - 5.0 ± 5.3%, P < 0.001) compared with the vehicle control (Group I). Transplantation of MSCs transduced with myr-Akt (Group III) resulted in further improvement in ΔLV EF (- 6.3 ± 15.1% versus 5.8 ± 11.3%, P < 0.001) and in Δarea of MI (6.8 ± 5.6% versus - 17.0 ± 7.6%, P < 0.001). Akt-MSCs were more resistant to apoptosis, and the levels of extracellular signal-regulated protein kinase (ERK) activation and vascular endothelial growth factor (VEGF) were higher in H₂O₂-stimulated Akt-MSCs. Conclusion: Cellular transplantation of Akt-MSCs further enhances the repair of injured myocardium compared to MSC transplantation alone by increasing the number of viable MSCs after cellular transplantation.

Original language	English
Pages (from-to)	530-542
Number of pages	13
Journal	Cardiovascular Research
Volume	70
Issue number	3
DOIs	https://doi.org/10.1016/j.cardiores.2006.02.016
Publication status	Published - 2006 Jun 1

Keywords

Akt
Mesenchymal stem cell
Myocardial infarction
Porcine

ASJC Scopus subject areas

Physiology
Cardiology and Cardiovascular Medicine
Physiology (medical)

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10.1016/j.cardiores.2006.02.016

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The effects of mesenchymal stem cells transduced with Akt in a porcine myocardial infarction model. / Lim, Sang Yup; Kim, Yong Sook; Ahn, Youngkeun; Jeong, Myung Ho; Hong, Moon Hwa; Joo, Soo Yeon; Nam, Kwang Il; Cho, Jeong Gwan; Kang, Peter M.; Park, Jong Chun.

In: Cardiovascular Research, Vol. 70, No. 3, 01.06.2006, p. 530-542.

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

@article{966fbc584c5d4ffca86417cfcb3c324f,

title = "The effects of mesenchymal stem cells transduced with Akt in a porcine myocardial infarction model",

abstract = "Objective: This study was designed to examine whether mesenchymal stem cells (MSCs) transduced with Akt enhance cardiac repair after transplantation into the ischemic porcine heart. Methods: MSCs isolated from porcine bone marrow and transduced with myr-Akt were transplanted into porcine hearts after experimental myocardial infarction (MI) using intracoronary injection [Group I, vehicle; Group II, MSCs; Group III, Akt-MSCs]. Myocardial single photon emission tomography (M-SPECT) was performed to assess myocardial function and the infarcted area. Pigs were also sacrificed for immunohistochemical characterization and histologic analysis. In addition, in vitro assays were performed to examine the resistance of Akt-MSCs to H2O2 stimulation. Results: Transplantation of MSCs into the ischemic porcine myocardium (Group II) increased the left ventricular ejection fraction (ΔLV EF; - 6.3 ± 15.1% versus 0.5 ± 6.4%, P < 0.001) and decreased the Δarea of MI (6.8 ± 5.6% versus - 5.0 ± 5.3%, P < 0.001) compared with the vehicle control (Group I). Transplantation of MSCs transduced with myr-Akt (Group III) resulted in further improvement in ΔLV EF (- 6.3 ± 15.1% versus 5.8 ± 11.3%, P < 0.001) and in Δarea of MI (6.8 ± 5.6% versus - 17.0 ± 7.6%, P < 0.001). Akt-MSCs were more resistant to apoptosis, and the levels of extracellular signal-regulated protein kinase (ERK) activation and vascular endothelial growth factor (VEGF) were higher in H2O2-stimulated Akt-MSCs. Conclusion: Cellular transplantation of Akt-MSCs further enhances the repair of injured myocardium compared to MSC transplantation alone by increasing the number of viable MSCs after cellular transplantation.",

keywords = "Akt, Mesenchymal stem cell, Myocardial infarction, Porcine",

author = "Lim, {Sang Yup} and Kim, {Yong Sook} and Youngkeun Ahn and Jeong, {Myung Ho} and Hong, {Moon Hwa} and Joo, {Soo Yeon} and Nam, {Kwang Il} and Cho, {Jeong Gwan} and Kang, {Peter M.} and Park, {Jong Chun}",

note = "Funding Information: This study was supported by the Korea Research Foundation 2004.",

year = "2006",

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day = "1",

doi = "10.1016/j.cardiores.2006.02.016",

language = "English",

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T1 - The effects of mesenchymal stem cells transduced with Akt in a porcine myocardial infarction model

AU - Lim, Sang Yup

AU - Kim, Yong Sook

AU - Ahn, Youngkeun

AU - Jeong, Myung Ho

AU - Hong, Moon Hwa

AU - Joo, Soo Yeon

AU - Nam, Kwang Il

AU - Cho, Jeong Gwan

AU - Kang, Peter M.

AU - Park, Jong Chun

N1 - Funding Information: This study was supported by the Korea Research Foundation 2004.

PY - 2006/6/1

Y1 - 2006/6/1

N2 - Objective: This study was designed to examine whether mesenchymal stem cells (MSCs) transduced with Akt enhance cardiac repair after transplantation into the ischemic porcine heart. Methods: MSCs isolated from porcine bone marrow and transduced with myr-Akt were transplanted into porcine hearts after experimental myocardial infarction (MI) using intracoronary injection [Group I, vehicle; Group II, MSCs; Group III, Akt-MSCs]. Myocardial single photon emission tomography (M-SPECT) was performed to assess myocardial function and the infarcted area. Pigs were also sacrificed for immunohistochemical characterization and histologic analysis. In addition, in vitro assays were performed to examine the resistance of Akt-MSCs to H2O2 stimulation. Results: Transplantation of MSCs into the ischemic porcine myocardium (Group II) increased the left ventricular ejection fraction (ΔLV EF; - 6.3 ± 15.1% versus 0.5 ± 6.4%, P < 0.001) and decreased the Δarea of MI (6.8 ± 5.6% versus - 5.0 ± 5.3%, P < 0.001) compared with the vehicle control (Group I). Transplantation of MSCs transduced with myr-Akt (Group III) resulted in further improvement in ΔLV EF (- 6.3 ± 15.1% versus 5.8 ± 11.3%, P < 0.001) and in Δarea of MI (6.8 ± 5.6% versus - 17.0 ± 7.6%, P < 0.001). Akt-MSCs were more resistant to apoptosis, and the levels of extracellular signal-regulated protein kinase (ERK) activation and vascular endothelial growth factor (VEGF) were higher in H2O2-stimulated Akt-MSCs. Conclusion: Cellular transplantation of Akt-MSCs further enhances the repair of injured myocardium compared to MSC transplantation alone by increasing the number of viable MSCs after cellular transplantation.

AB - Objective: This study was designed to examine whether mesenchymal stem cells (MSCs) transduced with Akt enhance cardiac repair after transplantation into the ischemic porcine heart. Methods: MSCs isolated from porcine bone marrow and transduced with myr-Akt were transplanted into porcine hearts after experimental myocardial infarction (MI) using intracoronary injection [Group I, vehicle; Group II, MSCs; Group III, Akt-MSCs]. Myocardial single photon emission tomography (M-SPECT) was performed to assess myocardial function and the infarcted area. Pigs were also sacrificed for immunohistochemical characterization and histologic analysis. In addition, in vitro assays were performed to examine the resistance of Akt-MSCs to H2O2 stimulation. Results: Transplantation of MSCs into the ischemic porcine myocardium (Group II) increased the left ventricular ejection fraction (ΔLV EF; - 6.3 ± 15.1% versus 0.5 ± 6.4%, P < 0.001) and decreased the Δarea of MI (6.8 ± 5.6% versus - 5.0 ± 5.3%, P < 0.001) compared with the vehicle control (Group I). Transplantation of MSCs transduced with myr-Akt (Group III) resulted in further improvement in ΔLV EF (- 6.3 ± 15.1% versus 5.8 ± 11.3%, P < 0.001) and in Δarea of MI (6.8 ± 5.6% versus - 17.0 ± 7.6%, P < 0.001). Akt-MSCs were more resistant to apoptosis, and the levels of extracellular signal-regulated protein kinase (ERK) activation and vascular endothelial growth factor (VEGF) were higher in H2O2-stimulated Akt-MSCs. Conclusion: Cellular transplantation of Akt-MSCs further enhances the repair of injured myocardium compared to MSC transplantation alone by increasing the number of viable MSCs after cellular transplantation.

KW - Akt

KW - Mesenchymal stem cell

KW - Myocardial infarction

KW - Porcine

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JF - Cardiovascular Research

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ER -

The effects of mesenchymal stem cells transduced with Akt in a porcine myocardial infarction model

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