Allogenic mesenchymal stem cell transplantation has a therapeutic effect in acute myocardial infarction in rats.
The goal of the study was to examine if allogenic mesenchymal stem cell (MSC) transplantation is a useful therapy for acute myocardial infarction (AMI). Buffer (control; group C, n=41), MSCs of male ACI rats (allogenic; group A, n=38, 5 x 10(6)), or MSCs of male LEW rats (syngenic; group S, n=40, 5 x 10(6)) were injected into the scar 15 min after myocardial infarction in female LEW rats. After 28 days, fractional left ventricular shortening significantly increased in groups A (21.3+/-1.7%, P=0.0467) and S (23.2+/-1.9%, P=0.0140), compared to group C (17.1+/-0.9%). Fibrosis in groups A and S was significantly lower. Quantitative PCR of the male-specific sry gene showed disappearance of donor cells within 28 days (5195+/-1975 cells). Secretion of vascular endothelial growth factor (VEGF) by MSCs was enhanced under hypoxic conditions in vitro. In groups A and S, the plasma VEGF concentration, VEGF level, and capillary density in recipient hearts increased after 28 days. Flow cytometry revealed the absence of B7 signal molecules on MSCs. A mixed lymphocyte reaction showed that ACI MSCs failed to stimulate proliferation of LEW lymphocytes. After 1 day after cell transplantation, transient increases in interleukin-1 beta and monocyte chemoattractant protein-1 in recipient hearts were enhanced in group A, with macrophage infiltration at the injection site. T cells remained at the level of normal tissue in all groups. We conclude that allogenic MSC transplantation therapy is useful for AMI. The donor MSCs disappear rapidly, but become a trigger of VEGF paracrine effect, without induction of immune rejection.
Imanishi
Yukiko
Y
Division of Cardiovascular Surgery, Department of Surgery, Graduate School of Medicine, Osaka University, Japan. y-imanishi@tissue.med.osaka-u.ac.jp
Saito
Atsuhiro
A
Komoda
Hiroshi
H
Kitagawa-Sakakida
Satoru
S
Miyagawa
Shigeru
S
Kondoh
Haruhiko
H
Ichikawa
Hajime
H
Sawa
Yoshiki
Y
D000818:Animals; D002452:Cell Count; D002470:Cell Survival; D004195:Disease Models, Animal; D004719:Endomyocardial Fibrosis / Q000000981:diagnostic imaging / Q000473:pathology; D005260:Female; D045164:Mesenchymal Stem Cell Transplantation; D009203:Myocardial Infarction / Q000139:chemically induced / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D009206:Myocardium / Q000473:pathology; D009389:Neovascularization, Pathologic; D019899:Paracrine Communication; D051381:Rats; D011917:Rats, Inbred Lew; D014184:Transplantation, Homologous; D014463:Ultrasonography; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D042461:Vascular Endothelial Growth Factor A