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First published online April 17, 2008
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2007-0715v1
26/6/1646    most recent
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Submitted on August 27, 2007
Accepted on March 31, 2008

TISSUE-SPECIFIC STEM CELLS

Transplantation of Bone Marrow-Derived Very Small Embryonic-like Stem Cells (Vsels) Attenuates Left Ventricular Dysfunction and Remodeling after Myocardial Infarction

Buddhadeb Dawn 1*, Sumit Tiwari 1, Magdalena J. Kucia 1, Ewa K. Zuba-Surma 1, Yiru Guo 1, Santosh K. SanganalMath 1, Ahmed Abdel-Latif 1, Greg Hunt 1, Robert J. Vincent 1, Hisham Taher 1, Nathan J. Reed 1, Mariusz Z. Ratajczak 1, Roberto Bolli 1

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


  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-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.

______________________________________________________________________________

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






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