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Mobilizing of haematopoietic stem cells to ischemic myocardium by plasmid mediated stromal-cell-derived factor-1alpha (SDF-1alpha) treatment.
Regul Pept. 2005 Feb 15; 125(1-3):1-8.RP

Abstract

A concentration gradient of stromal-cell-derived factor-1alpha (SDF-1alpha) is the major mechanism for homing of haematopoietic stem cells (HSCs) in bone marrow. We tested the hypothesis that a gene therapy using SDF-1alpha 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-1alpha plasmid (n=12) in 50 microl 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, 1x10(5) labeled cells were injected intravenously (i.v.) into saline mice (n=4) and SDF-1alpha 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-1alpha expression in SDF-1alpha-treated mouse ischemic hearts compared to saline-treated hearts and other tissues. In the SDF-1alpha plasmid-treated hearts, SDF-1alpha is overexpressed in the periinfarct zone. The labeled stem cells engrafted to the SDF-1alpha 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-1alpha-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-1alpha or saline treatment. Following myocardial infarction, treatment with SDF-1alpha recruits stem cells to damaged heart where they may have a role in repairing and regeneration. The gene therapy with an SDF-1alpha vector offers a promising therapeutic strategy for mobilizing stem cells to the ischemic myocardium.

Authors+Show Affiliations

Department of Pediatrics, College of Medicine and All Children's Hospital Research Institute, University of South Florida, 140 7th Ave South, CRI 2015, St. Petersburg, Florida, 33701, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

15582707

Citation

Tang, Yao Liang, et al. "Mobilizing of Haematopoietic Stem Cells to Ischemic Myocardium By Plasmid Mediated Stromal-cell-derived Factor-1alpha (SDF-1alpha) Treatment." Regulatory Peptides, vol. 125, no. 1-3, 2005, pp. 1-8.
Tang YL, Qian K, Zhang YC, et al. Mobilizing of haematopoietic stem cells to ischemic myocardium by plasmid mediated stromal-cell-derived factor-1alpha (SDF-1alpha) treatment. Regul Pept. 2005;125(1-3):1-8.
Tang, Y. L., Qian, K., Zhang, Y. C., Shen, L., & Phillips, M. I. (2005). Mobilizing of haematopoietic stem cells to ischemic myocardium by plasmid mediated stromal-cell-derived factor-1alpha (SDF-1alpha) treatment. Regulatory Peptides, 125(1-3), 1-8.
Tang YL, et al. Mobilizing of Haematopoietic Stem Cells to Ischemic Myocardium By Plasmid Mediated Stromal-cell-derived Factor-1alpha (SDF-1alpha) Treatment. Regul Pept. 2005 Feb 15;125(1-3):1-8. PubMed PMID: 15582707.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mobilizing of haematopoietic stem cells to ischemic myocardium by plasmid mediated stromal-cell-derived factor-1alpha (SDF-1alpha) treatment. AU - Tang,Yao Liang, AU - Qian,Keping, AU - Zhang,Y Clare, AU - Shen,Leping, AU - Phillips,M Ian, PY - 2004/09/09/received PY - 2004/10/21/revised PY - 2004/10/21/accepted PY - 2004/12/8/pubmed PY - 2005/5/25/medline PY - 2004/12/8/entrez SP - 1 EP - 8 JF - Regulatory peptides JO - Regul Pept VL - 125 IS - 1-3 N2 - A concentration gradient of stromal-cell-derived factor-1alpha (SDF-1alpha) is the major mechanism for homing of haematopoietic stem cells (HSCs) in bone marrow. We tested the hypothesis that a gene therapy using SDF-1alpha 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-1alpha plasmid (n=12) in 50 microl 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, 1x10(5) labeled cells were injected intravenously (i.v.) into saline mice (n=4) and SDF-1alpha 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-1alpha expression in SDF-1alpha-treated mouse ischemic hearts compared to saline-treated hearts and other tissues. In the SDF-1alpha plasmid-treated hearts, SDF-1alpha is overexpressed in the periinfarct zone. The labeled stem cells engrafted to the SDF-1alpha 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-1alpha-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-1alpha or saline treatment. Following myocardial infarction, treatment with SDF-1alpha recruits stem cells to damaged heart where they may have a role in repairing and regeneration. The gene therapy with an SDF-1alpha vector offers a promising therapeutic strategy for mobilizing stem cells to the ischemic myocardium. SN - 0167-0115 UR - https://www.unboundmedicine.com/medline/citation/15582707/Mobilizing_of_haematopoietic_stem_cells_to_ischemic_myocardium_by_plasmid_mediated_stromal_cell_derived_factor_1alpha__SDF_1alpha__treatment_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0167-0115(04)00397-0 DB - PRIME DP - Unbound Medicine ER -