Transplantation of bone marrow-derived very small embryonic-like stem cells attenuates left ventricular dysfunction and remodeling after myocardial infarction.
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.
Dawn
Buddhadeb
B
Institute of Molecular Cardiology, University of Louisville, Louisville, Kentucky 40292, USA. buddha@louisville.edu
Tiwari
Sumit
S
Kucia
Magdalena J
MJ
Zuba-Surma
Ewa K
EK
Guo
Yiru
Y
Sanganalmath
Santosh K
SK
Abdel-Latif
Ahmed
A
Hunt
Greg
G
Vincent
Robert J
RJ
Taher
Hisham
H
Reed
Nathan J
NJ
Ratajczak
Mariusz Z
MZ
Bolli
Roberto
R
D000818:Animals; D006332:Cardiomegaly / Q000517:prevention & control*; D004195:Disease Models, Animal; D053595:Embryonic Stem Cells / Q000166:cytology / Q000502:physiology*; D005434:Flow Cytometry; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000032:analysis / Q000235:genetics; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D008297:Male; D051379:Mice; D009203:Myocardial Infarction / Q000150:complications* / Q000473:pathology; D018487:Ventricular Dysfunction, Left / Q000209:etiology / Q000517:prevention & control*; D020257:Ventricular Remodeling
D049452:Green Fluorescent Proteins