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PMID: 18420834 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Transplantation of bone marrow-derived very small embryonic-like stem cells attenuates left ventricular dysfunction and remodeling after myocardial infarction.

Stem cells (Dayton, Ohio) ·Vol. 26 ·No. 6 ·2008-06-00 ·Pages 1646-55

Dawn B, Tiwari S, Kucia MJ, Zuba-Surma EK, Guo Y, Sanganalmath SK, Abdel-Latif A, Hunt G, Vincent RJ, Taher H, Reed NJ, Ratajczak MZ, Bolli R

Abstract

Adult bone marrow (BM) contains Sca-1+/Lin-/CD45- very small embryonic-like stem cells (VSELs) that express markers of several lineages, including cardiac markers, and differentiate into cardiomyocytes in vitro. We examined whether BM-derived VSELs promote myocardial repair after a reperfused myocardial infarction (MI). Mice underwent a 30-minute coronary occlusion followed by reperfusion and received intramyocardial injection of vehicle (n= 11), 1 x 10(5) Sca-1+/Lin-/CD45+ enhanced green fluorescent protein (EGFP)-labeled hematopoietic stem cells (n= 13 [cell control group]), or 1 x 10(4) Sca-1+/Lin-/CD45- EGFP-labeled cells (n= 14 [VSEL-treated group]) at 48 hours after MI. At 35 days after MI, VSEL-treated mice exhibited improved global and regional left ventricular (LV) systolic function (echocardiography) and attenuated myocyte hypertrophy in surviving tissue (histology and echocardiography) compared with vehicle-treated controls. In contrast, transplantation of Sca-1+/Lin-/CD45+ cells failed to confer any functional or structural benefits. Scattered EGFP+ myocytes and capillaries were present in the infarct region in VSEL-treated mice, but their numbers were very small. These results indicate that transplantation of a relatively small number of CD45- VSELs is sufficient to improve LV function and alleviate myocyte hypertrophy after MI, supporting the potential therapeutic utility of these cells for cardiac repair. Disclosure of potential conflicts of interest is found at the end of this article.

MeSH Terms
Animals Cardiomegaly/prevention & control Disease Models, Animal Embryonic Stem Cells/cytology,physiology Flow Cytometry Genes, Reporter Green Fluorescent Proteins/analysis,genetics Hematopoietic Stem Cell Transplantation/methods Male Mice Myocardial Infarction/complications,pathology Ventricular Dysfunction, Left/etiology,prevention & control Ventricular Remodeling
Chemicals
Green Fluorescent Proteins
Authors & Affiliations
13 authors, click to expand affiliations / ORCID
Dawn Buddhadeb
Institute of Molecular Cardiology, University of Louisville, Louisville, Kentucky 40292, USA. [email protected]
Tiwari Sumit
Kucia Magdalena J
Zuba-Surma Ewa K
Guo Yiru
Sanganalmath Santosh K
Abdel-Latif Ahmed
Hunt Greg
Vincent Robert J
Taher Hisham
Reed Nathan J
Ratajczak Mariusz Z
Bolli Roberto
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Article Info
Journal
Stem cells (Dayton, Ohio)
Abbr.
Stem Cells
ISSN
1549-4918
Published
2008-06-00
Epub
2008-00-17
Pages
1646-55
Language
English
Region
United States
NLM ID
9304532
PMCID
PMC3682652
Subset
IM
Grants
NHLBI NIH HHS · R37 HL055757 · United States
NHLBI NIH HHS · R01 HL076794 · United States
NIDDK NIH HHS · R01 DK074720 · United States
NHLBI NIH HHS · HL-68088 · United States
NHLBI NIH HHS · HL-70897 · United States
NHLBI NIH HHS · R01-HL-72410 · United States
NHLBI NIH HHS · R01 HL072410 · United States
NHLBI NIH HHS · HL-55757 · United States
NCI NIH HHS · R01 CA106281 · United States
NHLBI NIH HHS · R01 HL068088 · United States
NHLBI NIH HHS · R01 HL055757 · United States
NCI NIH HHS · CA-106281 · United States
NHLBI NIH HHS · HL-78825 · United States
NHLBI NIH HHS · R01 HL070897 · United States
NIDDK NIH HHS · DK-074720 · United States
NHLBI NIH HHS · P01 HL078825 · United States
NHLBI NIH HHS · HL-76794 · United States
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