TY - JOUR
T1 - Transplantation of bone marrow-derived very small embryonic-like stem cells attenuates left ventricular dysfunction and remodeling after myocardial infarction
AU - Dawn, Buddhadeb
AU - Tiwari, Sumit
AU - Kucia, Magdalena J.
AU - Zuba-Surma, Ewa K.
AU - Guo, Yiru
AU - Sanganalmath, Santosh K.
AU - Abdel-Latif, Ahmed
AU - Hunt, Greg
AU - Vincent, Robert J.
AU - Taher, Hisham
AU - Reed, Nathan J.
AU - Ratajczak, Mariusz Z.
AU - Bolli, Roberto
PY - 2008/6
Y1 - 2008/6
N2 - 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 × 105 Sca-1+/Lin-/CD45+ enhanced green fluorescent protein (EGFP)-labeled hematopoietic stem cells (n = 13 [cell control group]), or 1 × 104 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.
AB - 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 × 105 Sca-1+/Lin-/CD45+ enhanced green fluorescent protein (EGFP)-labeled hematopoietic stem cells (n = 13 [cell control group]), or 1 × 104 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.
KW - Bone marrow
KW - Left ventricular function
KW - Myocardial infarction
KW - Myocardial regeneration
KW - Stem cell
KW - Very small embryonic-like stem cell
UR - http://www.scopus.com/inward/record.url?scp=48649104373&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=48649104373&partnerID=8YFLogxK
U2 - 10.1634/stemcells.2007-0715
DO - 10.1634/stemcells.2007-0715
M3 - Article
C2 - 18420834
AN - SCOPUS:48649104373
SN - 1066-5099
VL - 26
SP - 1646
EP - 1655
JO - Stem Cells
JF - Stem Cells
IS - 6
ER -