Stable therapeutic effects of mesenchymal stem cell-based multiple gene delivery for cardiac repair

Jiang Shujia, Husnain Khawaja Haider, Niagara Muhammad Idris, Gang Lu, Muhammad Ashraf

Research output: Contribution to journalArticle

73 Citations (Scopus)

Abstract

Aims: We have previously shown that transplantation of mesenchymal stem cells (MSCs) co-overexpressing angiopoietin-1 (Ang-1) and Akt prevented cell apoptosis, enhanced angiogenesis, and improved left ventricular heart function. The present study was designed to determine the persistence of therapeutic benefits on longer term basis. Methods and results: Acute myocardial infarction model was developed in 30 young female Fischer-344 rats by permanent ligation of the left anterior descending coronary artery. The animals were grouped (n = 10) to receive 70 μL Dulbecco's modified Eagle's medium (DMEM) without cells (DMEM group 1) or containing 3 × 106 non-transduced male MSCs (MSC group 2) or transduced MSCs co-overexpressing Ang-1 and Akt (MAA group 3). The injections were carried out intramyocardially in the free wall of left ventricle at multiple sites. Three months after cell transplantation, real-time polymerase chain reaction for the rat sry gene, confocal imaging, and immunohistochemical studies revealed the extensive survival and myogenic differentiation of the PKH67-labelled cell graft. Blood vessel density was significantly higher in the MAA group (P < 0.05) at 3 months compared with the other groups. Blood vessel maturation index as determined by double-fluorescent immunostaining for vWFactor VIII and smooth muscle actin showed that most of the newly formed vessels matured to develop a smooth muscle covering in MAA group. Sonographic assessment of heart function showed that heart function deteriorated in the DMEM group, whereas the functional benefits were stable over a period of 3 months following transplantation of transfected cells. Conclusion: Engraftment of genetically modified MSCs co-overexpressing Ang-1 and Akt produced long-term histological and functional benefits in an infarcted heart.

Original languageEnglish (US)
Pages (from-to)525-533
Number of pages9
JournalCardiovascular Research
Volume77
Issue number3
DOIs
StatePublished - Feb 1 2008

Fingerprint

Therapeutic Uses
Angiopoietin-1
Mesenchymal Stromal Cells
Eagles
Cell Transplantation
Genes
Smooth Muscle
Blood Vessels
sry Genes
Mesenchymal Stem Cell Transplantation
Inbred F344 Rats
Left Ventricular Function
Heart Ventricles
Ligation
Actins
Real-Time Polymerase Chain Reaction
Coronary Vessels
Myocardial Infarction
Apoptosis
Transplants

Keywords

  • Apoptosis
  • Cell differentiation
  • Gene therapy
  • Stem cells

ASJC Scopus subject areas

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

Cite this

Stable therapeutic effects of mesenchymal stem cell-based multiple gene delivery for cardiac repair. / Shujia, Jiang; Haider, Husnain Khawaja; Idris, Niagara Muhammad; Lu, Gang; Ashraf, Muhammad.

In: Cardiovascular Research, Vol. 77, No. 3, 01.02.2008, p. 525-533.

Research output: Contribution to journalArticle

Shujia, Jiang ; Haider, Husnain Khawaja ; Idris, Niagara Muhammad ; Lu, Gang ; Ashraf, Muhammad. / Stable therapeutic effects of mesenchymal stem cell-based multiple gene delivery for cardiac repair. In: Cardiovascular Research. 2008 ; Vol. 77, No. 3. pp. 525-533.
@article{c03c4e63904c4d74adcb2bbc5c5e43e6,
title = "Stable therapeutic effects of mesenchymal stem cell-based multiple gene delivery for cardiac repair",
abstract = "Aims: We have previously shown that transplantation of mesenchymal stem cells (MSCs) co-overexpressing angiopoietin-1 (Ang-1) and Akt prevented cell apoptosis, enhanced angiogenesis, and improved left ventricular heart function. The present study was designed to determine the persistence of therapeutic benefits on longer term basis. Methods and results: Acute myocardial infarction model was developed in 30 young female Fischer-344 rats by permanent ligation of the left anterior descending coronary artery. The animals were grouped (n = 10) to receive 70 μL Dulbecco's modified Eagle's medium (DMEM) without cells (DMEM group 1) or containing 3 × 106 non-transduced male MSCs (MSC group 2) or transduced MSCs co-overexpressing Ang-1 and Akt (MAA group 3). The injections were carried out intramyocardially in the free wall of left ventricle at multiple sites. Three months after cell transplantation, real-time polymerase chain reaction for the rat sry gene, confocal imaging, and immunohistochemical studies revealed the extensive survival and myogenic differentiation of the PKH67-labelled cell graft. Blood vessel density was significantly higher in the MAA group (P < 0.05) at 3 months compared with the other groups. Blood vessel maturation index as determined by double-fluorescent immunostaining for vWFactor VIII and smooth muscle actin showed that most of the newly formed vessels matured to develop a smooth muscle covering in MAA group. Sonographic assessment of heart function showed that heart function deteriorated in the DMEM group, whereas the functional benefits were stable over a period of 3 months following transplantation of transfected cells. Conclusion: Engraftment of genetically modified MSCs co-overexpressing Ang-1 and Akt produced long-term histological and functional benefits in an infarcted heart.",
keywords = "Apoptosis, Cell differentiation, Gene therapy, Stem cells",
author = "Jiang Shujia and Haider, {Husnain Khawaja} and Idris, {Niagara Muhammad} and Gang Lu and Muhammad Ashraf",
year = "2008",
month = "2",
day = "1",
doi = "10.1093/cvr/cvm077",
language = "English (US)",
volume = "77",
pages = "525--533",
journal = "Cardiovascular Research",
issn = "0008-6363",
publisher = "Oxford University Press",
number = "3",

}

TY - JOUR

T1 - Stable therapeutic effects of mesenchymal stem cell-based multiple gene delivery for cardiac repair

AU - Shujia, Jiang

AU - Haider, Husnain Khawaja

AU - Idris, Niagara Muhammad

AU - Lu, Gang

AU - Ashraf, Muhammad

PY - 2008/2/1

Y1 - 2008/2/1

N2 - Aims: We have previously shown that transplantation of mesenchymal stem cells (MSCs) co-overexpressing angiopoietin-1 (Ang-1) and Akt prevented cell apoptosis, enhanced angiogenesis, and improved left ventricular heart function. The present study was designed to determine the persistence of therapeutic benefits on longer term basis. Methods and results: Acute myocardial infarction model was developed in 30 young female Fischer-344 rats by permanent ligation of the left anterior descending coronary artery. The animals were grouped (n = 10) to receive 70 μL Dulbecco's modified Eagle's medium (DMEM) without cells (DMEM group 1) or containing 3 × 106 non-transduced male MSCs (MSC group 2) or transduced MSCs co-overexpressing Ang-1 and Akt (MAA group 3). The injections were carried out intramyocardially in the free wall of left ventricle at multiple sites. Three months after cell transplantation, real-time polymerase chain reaction for the rat sry gene, confocal imaging, and immunohistochemical studies revealed the extensive survival and myogenic differentiation of the PKH67-labelled cell graft. Blood vessel density was significantly higher in the MAA group (P < 0.05) at 3 months compared with the other groups. Blood vessel maturation index as determined by double-fluorescent immunostaining for vWFactor VIII and smooth muscle actin showed that most of the newly formed vessels matured to develop a smooth muscle covering in MAA group. Sonographic assessment of heart function showed that heart function deteriorated in the DMEM group, whereas the functional benefits were stable over a period of 3 months following transplantation of transfected cells. Conclusion: Engraftment of genetically modified MSCs co-overexpressing Ang-1 and Akt produced long-term histological and functional benefits in an infarcted heart.

AB - Aims: We have previously shown that transplantation of mesenchymal stem cells (MSCs) co-overexpressing angiopoietin-1 (Ang-1) and Akt prevented cell apoptosis, enhanced angiogenesis, and improved left ventricular heart function. The present study was designed to determine the persistence of therapeutic benefits on longer term basis. Methods and results: Acute myocardial infarction model was developed in 30 young female Fischer-344 rats by permanent ligation of the left anterior descending coronary artery. The animals were grouped (n = 10) to receive 70 μL Dulbecco's modified Eagle's medium (DMEM) without cells (DMEM group 1) or containing 3 × 106 non-transduced male MSCs (MSC group 2) or transduced MSCs co-overexpressing Ang-1 and Akt (MAA group 3). The injections were carried out intramyocardially in the free wall of left ventricle at multiple sites. Three months after cell transplantation, real-time polymerase chain reaction for the rat sry gene, confocal imaging, and immunohistochemical studies revealed the extensive survival and myogenic differentiation of the PKH67-labelled cell graft. Blood vessel density was significantly higher in the MAA group (P < 0.05) at 3 months compared with the other groups. Blood vessel maturation index as determined by double-fluorescent immunostaining for vWFactor VIII and smooth muscle actin showed that most of the newly formed vessels matured to develop a smooth muscle covering in MAA group. Sonographic assessment of heart function showed that heart function deteriorated in the DMEM group, whereas the functional benefits were stable over a period of 3 months following transplantation of transfected cells. Conclusion: Engraftment of genetically modified MSCs co-overexpressing Ang-1 and Akt produced long-term histological and functional benefits in an infarcted heart.

KW - Apoptosis

KW - Cell differentiation

KW - Gene therapy

KW - Stem cells

UR - http://www.scopus.com/inward/record.url?scp=38849108084&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=38849108084&partnerID=8YFLogxK

U2 - 10.1093/cvr/cvm077

DO - 10.1093/cvr/cvm077

M3 - Article

VL - 77

SP - 525

EP - 533

JO - Cardiovascular Research

JF - Cardiovascular Research

SN - 0008-6363

IS - 3

ER -