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

Sang Yeob 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 journalArticle

146 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 languageEnglish
Pages (from-to)530-542
Number of pages13
JournalCardiovascular Research
Volume70
Issue number3
DOIs
Publication statusPublished - 2006 Jun 1
Externally publishedYes

Fingerprint

Mesenchymal Stromal Cells
Swine
Myocardial Infarction
Mesenchymal Stem Cell Transplantation
Myocardium
Transplantation
Extracellular Signal-Regulated MAP Kinases
Single-Photon Emission-Computed Tomography
Photons
Stroke Volume
Protein Kinases
Vascular Endothelial Growth Factor A
Bone Marrow
Tomography
Apoptosis
Control Groups
Injections

Keywords

  • Akt
  • Mesenchymal stem cell
  • Myocardial infarction
  • Porcine

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

The effects of mesenchymal stem cells transduced with Akt in a porcine myocardial infarction model. / Lim, Sang Yeob; 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 journalArticle

Lim, SY, Kim, YS, Ahn, Y, Jeong, MH, Hong, MH, Joo, SY, Nam, KI, Cho, JG, Kang, PM & Park, JC 2006, 'The effects of mesenchymal stem cells transduced with Akt in a porcine myocardial infarction model', Cardiovascular Research, vol. 70, no. 3, pp. 530-542. https://doi.org/10.1016/j.cardiores.2006.02.016
Lim, Sang Yeob ; 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. / The effects of mesenchymal stem cells transduced with Akt in a porcine myocardial infarction model. In: Cardiovascular Research. 2006 ; Vol. 70, No. 3. pp. 530-542.
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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.",
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AU - Lim, Sang Yeob

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

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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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