Mobilizing of haematopoietic stem cells to ischemic myocardium by plasmid-mediated stromal-cell-derived factor-1α treatment

Yao Liang Tang, Keping Qian, Y. Clare Zhang, Leping Shen, M. Ian Phillips

Research output: Contribution to journalArticle

61 Citations (Scopus)

Abstract

A concentration gradient of stromal-cell-derived factor-1α (SDF-1α) is the major mechanism for homing of haematopoietic stem cells (HSCs) in bone marrow. We tested the hypothesis that a gene therapy using SDF-1α can enhance HSCs recruiting to the heart upon myocardial infarction (MI). Adult mice with surgically induced myocardial ischemia were injected intramyocardially with either saline (n=12) or SDF-1α plasmid (n=12) in 50 μl volume in the ischemic border zone of the infarcted heart 2 weeks after myocardial infarction. Donor Lin-c-kit+ HSCs from isogenic BalB/c mice were harvested, sorted through magnetic cell sorting (MACS) and labeled with PKH26 Red. Three days after plasmid or saline injection, 1×105 labeled cells were injected intravenously (i.v.) into saline mice (n=4) and SDF-1α plasmid mice (n=4). The hearts and other tissue were removed for Western blot assay 2 weeks after plasmid or saline treatment. The labeled Lin-c-kit+ cells were identified with immunofluoresent staining and endogenous c-kit+ cells were identified by immunohistochemical staining. In mice killed at 1 month postinfarct, Western blot showed higher levels of SDF-1α expression in SDF-1α-treated mouse ischemic hearts compared to saline-treated hearts and other tissues. In the SDF-1α plasmid-treated hearts, SDF-1α is overexpressed in the periinfarct zone. The labeled stem cells engrafted to the SDF-1α positive site in the myocardium. There was also evidence for endogenous stem cell recruiting. The density of c-kit+ cells in border zone, an index of endogenous stem cell mobilization, was significantly higher in the SDF-1α-treated group than in the saline group (14.63±1.068 cells/hpf vs. 11.31±0.65 cells/hpf, P=0.013) at 2 weeks after SDF-1α or saline treatment. Following myocardial infarction, treatment with SDF-1α recruits stem cells to damaged heart where they may have a role in repairing and regeneration. The gene therapy with an SDF-1α vector offers a promising therapeutic strategy for mobilizing stem cells to the ischemic myocardium.

Original languageEnglish (US)
Pages (from-to)1-8
Number of pages8
JournalRegulatory Peptides
Volume125
Issue number1-3
DOIs
StatePublished - Feb 15 2005
Externally publishedYes

Fingerprint

Chemokine CXCL12
Hematopoietic Stem Cells
Stem cells
Myocardium
Plasmids
Stem Cells
Therapeutics
Myocardial Infarction
Gene therapy
Genetic Therapy
Western Blotting
Hematopoietic Stem Cell Mobilization
Staining and Labeling
Tissue
Myocardial Ischemia
Regeneration
Sorting
Bone Marrow

Keywords

  • Gene therapy
  • SDF-1α
  • Stem cell mobilization

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Endocrinology
  • Clinical Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Mobilizing of haematopoietic stem cells to ischemic myocardium by plasmid-mediated stromal-cell-derived factor-1α treatment. / Tang, Yao Liang; Qian, Keping; Zhang, Y. Clare; Shen, Leping; Phillips, M. Ian.

In: Regulatory Peptides, Vol. 125, No. 1-3, 15.02.2005, p. 1-8.

Research output: Contribution to journalArticle

Tang, Yao Liang ; Qian, Keping ; Zhang, Y. Clare ; Shen, Leping ; Phillips, M. Ian. / Mobilizing of haematopoietic stem cells to ischemic myocardium by plasmid-mediated stromal-cell-derived factor-1α treatment. In: Regulatory Peptides. 2005 ; Vol. 125, No. 1-3. pp. 1-8.
@article{90ecc76b961747869fd5c8c3a3b9eac2,
title = "Mobilizing of haematopoietic stem cells to ischemic myocardium by plasmid-mediated stromal-cell-derived factor-1α treatment",
abstract = "A concentration gradient of stromal-cell-derived factor-1α (SDF-1α) is the major mechanism for homing of haematopoietic stem cells (HSCs) in bone marrow. We tested the hypothesis that a gene therapy using SDF-1α can enhance HSCs recruiting to the heart upon myocardial infarction (MI). Adult mice with surgically induced myocardial ischemia were injected intramyocardially with either saline (n=12) or SDF-1α plasmid (n=12) in 50 μl volume in the ischemic border zone of the infarcted heart 2 weeks after myocardial infarction. Donor Lin-c-kit+ HSCs from isogenic BalB/c mice were harvested, sorted through magnetic cell sorting (MACS) and labeled with PKH26 Red. Three days after plasmid or saline injection, 1×105 labeled cells were injected intravenously (i.v.) into saline mice (n=4) and SDF-1α plasmid mice (n=4). The hearts and other tissue were removed for Western blot assay 2 weeks after plasmid or saline treatment. The labeled Lin-c-kit+ cells were identified with immunofluoresent staining and endogenous c-kit+ cells were identified by immunohistochemical staining. In mice killed at 1 month postinfarct, Western blot showed higher levels of SDF-1α expression in SDF-1α-treated mouse ischemic hearts compared to saline-treated hearts and other tissues. In the SDF-1α plasmid-treated hearts, SDF-1α is overexpressed in the periinfarct zone. The labeled stem cells engrafted to the SDF-1α positive site in the myocardium. There was also evidence for endogenous stem cell recruiting. The density of c-kit+ cells in border zone, an index of endogenous stem cell mobilization, was significantly higher in the SDF-1α-treated group than in the saline group (14.63±1.068 cells/hpf vs. 11.31±0.65 cells/hpf, P=0.013) at 2 weeks after SDF-1α or saline treatment. Following myocardial infarction, treatment with SDF-1α recruits stem cells to damaged heart where they may have a role in repairing and regeneration. The gene therapy with an SDF-1α vector offers a promising therapeutic strategy for mobilizing stem cells to the ischemic myocardium.",
keywords = "Gene therapy, SDF-1α, Stem cell mobilization",
author = "Tang, {Yao Liang} and Keping Qian and Zhang, {Y. Clare} and Leping Shen and Phillips, {M. Ian}",
year = "2005",
month = "2",
day = "15",
doi = "10.1016/j.regpep.2004.10.014",
language = "English (US)",
volume = "125",
pages = "1--8",
journal = "Regulatory Peptides",
issn = "0167-0115",
publisher = "Elsevier",
number = "1-3",

}

TY - JOUR

T1 - Mobilizing of haematopoietic stem cells to ischemic myocardium by plasmid-mediated stromal-cell-derived factor-1α treatment

AU - Tang, Yao Liang

AU - Qian, Keping

AU - Zhang, Y. Clare

AU - Shen, Leping

AU - Phillips, M. Ian

PY - 2005/2/15

Y1 - 2005/2/15

N2 - A concentration gradient of stromal-cell-derived factor-1α (SDF-1α) is the major mechanism for homing of haematopoietic stem cells (HSCs) in bone marrow. We tested the hypothesis that a gene therapy using SDF-1α can enhance HSCs recruiting to the heart upon myocardial infarction (MI). Adult mice with surgically induced myocardial ischemia were injected intramyocardially with either saline (n=12) or SDF-1α plasmid (n=12) in 50 μl volume in the ischemic border zone of the infarcted heart 2 weeks after myocardial infarction. Donor Lin-c-kit+ HSCs from isogenic BalB/c mice were harvested, sorted through magnetic cell sorting (MACS) and labeled with PKH26 Red. Three days after plasmid or saline injection, 1×105 labeled cells were injected intravenously (i.v.) into saline mice (n=4) and SDF-1α plasmid mice (n=4). The hearts and other tissue were removed for Western blot assay 2 weeks after plasmid or saline treatment. The labeled Lin-c-kit+ cells were identified with immunofluoresent staining and endogenous c-kit+ cells were identified by immunohistochemical staining. In mice killed at 1 month postinfarct, Western blot showed higher levels of SDF-1α expression in SDF-1α-treated mouse ischemic hearts compared to saline-treated hearts and other tissues. In the SDF-1α plasmid-treated hearts, SDF-1α is overexpressed in the periinfarct zone. The labeled stem cells engrafted to the SDF-1α positive site in the myocardium. There was also evidence for endogenous stem cell recruiting. The density of c-kit+ cells in border zone, an index of endogenous stem cell mobilization, was significantly higher in the SDF-1α-treated group than in the saline group (14.63±1.068 cells/hpf vs. 11.31±0.65 cells/hpf, P=0.013) at 2 weeks after SDF-1α or saline treatment. Following myocardial infarction, treatment with SDF-1α recruits stem cells to damaged heart where they may have a role in repairing and regeneration. The gene therapy with an SDF-1α vector offers a promising therapeutic strategy for mobilizing stem cells to the ischemic myocardium.

AB - A concentration gradient of stromal-cell-derived factor-1α (SDF-1α) is the major mechanism for homing of haematopoietic stem cells (HSCs) in bone marrow. We tested the hypothesis that a gene therapy using SDF-1α can enhance HSCs recruiting to the heart upon myocardial infarction (MI). Adult mice with surgically induced myocardial ischemia were injected intramyocardially with either saline (n=12) or SDF-1α plasmid (n=12) in 50 μl volume in the ischemic border zone of the infarcted heart 2 weeks after myocardial infarction. Donor Lin-c-kit+ HSCs from isogenic BalB/c mice were harvested, sorted through magnetic cell sorting (MACS) and labeled with PKH26 Red. Three days after plasmid or saline injection, 1×105 labeled cells were injected intravenously (i.v.) into saline mice (n=4) and SDF-1α plasmid mice (n=4). The hearts and other tissue were removed for Western blot assay 2 weeks after plasmid or saline treatment. The labeled Lin-c-kit+ cells were identified with immunofluoresent staining and endogenous c-kit+ cells were identified by immunohistochemical staining. In mice killed at 1 month postinfarct, Western blot showed higher levels of SDF-1α expression in SDF-1α-treated mouse ischemic hearts compared to saline-treated hearts and other tissues. In the SDF-1α plasmid-treated hearts, SDF-1α is overexpressed in the periinfarct zone. The labeled stem cells engrafted to the SDF-1α positive site in the myocardium. There was also evidence for endogenous stem cell recruiting. The density of c-kit+ cells in border zone, an index of endogenous stem cell mobilization, was significantly higher in the SDF-1α-treated group than in the saline group (14.63±1.068 cells/hpf vs. 11.31±0.65 cells/hpf, P=0.013) at 2 weeks after SDF-1α or saline treatment. Following myocardial infarction, treatment with SDF-1α recruits stem cells to damaged heart where they may have a role in repairing and regeneration. The gene therapy with an SDF-1α vector offers a promising therapeutic strategy for mobilizing stem cells to the ischemic myocardium.

KW - Gene therapy

KW - SDF-1α

KW - Stem cell mobilization

UR - http://www.scopus.com/inward/record.url?scp=9944249035&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=9944249035&partnerID=8YFLogxK

U2 - 10.1016/j.regpep.2004.10.014

DO - 10.1016/j.regpep.2004.10.014

M3 - Article

VL - 125

SP - 1

EP - 8

JO - Regulatory Peptides

JF - Regulatory Peptides

SN - 0167-0115

IS - 1-3

ER -