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TISSUE-SPECIFIC STEM CELLS |
1 From the Institute of Molecular Cardiology and the Stem Cell Biology Program, University of Louisville, Louisville, KY 40292, USA
* To whom correspondence should be addressed. E-mail: buddha{at}louisville.edu.
Correspondence may also be addressed to Roberto Bolli at rbolli@louisville.edu
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Abstract |
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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-min coronary occlusion followed by reperfusion and received intramyocardial injection of vehicle (n=11), 1x105 Sca-1+/Lin-/CD45+ EGFP-labeled hematopoietic stem cells (n=13 [cell control group]), or 1x104 Sca-1+/Lin-/CD45- EGFP-labeled cells (n=14 [VSEL-treated group]) at 48 h after MI. At 35 d 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.
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Author contributions: B.D.: Conception and design, financial support, administrative support, provision of study material or patients, collection and/or assembly of data, data analysis and interpretation, manuscript writing, final approval of manuscript; S.T.: Collection and/or assembly of data, data analysis and interpretation; M.K.: Conception and design, provision of study material or patients, collection and/or assembly of data, data analysis and interpretation; E.K.Z.: Conception and design, provision of study material or patients, collection and/or assembly of data, data analysis and interpretation; Y.G.: Provision of study material or patients, collection and/or assembly of data, data analysis and interpretation; S.K.S.: Collection and/or assembly of data, data analysis and interpretation; A.A.: Collection and/or assembly of data, data analysis and interpretation; G.H.: Provision of study material or patients, collection and/or assembly of data, data analysis and interpretation; R.J.V.: Administrative support, provision of study material or patients, collection and/or assembly of data; H.T.: Collection and/or assembly of data, data analysis and interpretation; N.J.R.: Collection and/or assembly of data; M.Z.R.: Conception and design, financial support, provision of study material or patients, manuscript writing, final approval of manuscript; R.B.: Conception and design, financial support, administrative support, manuscript writing, final approval of manuscript.
Key Words. Myocardial infarction, myocardial regeneration, VSEL, stem cell, bone marrow, left ventricular function
This article has been cited by other articles:
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  H. Reinecke, E. Minami, W.-Z. Zhu, and M. A. Laflamme Cardiogenic Differentiation and Transdifferentiation of Progenitor Cells Circ. Res., November 7, 2008; 103(10): 1058 - 1071. [Abstract] [Full Text] [PDF]
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