Migration of mesenchymal stem cells to heart allografts during chronic rejection.
BACKGROUND
Mesenchymal stem cells (MSC) are pluripotent progenitors for a variety of cell types, including fibroblasts and muscle cells. Their involvement in the tissue repair of allografts during the development of chronic rejection has been hypothesized, but not yet substantiated, by experimental evidence.


METHODS
Rat MSC were isolated from circulation using an aortic pouch allograft as a trapping device. The plasticity of these cells was examined in differentiation cultures. One of the resulting MSC lines was immortalized and transduced to express a marker gene. The -labeled cells were then transferred to F344 rats bearing Lewis (LEW) cardiac allografts to measure their localization and contribution to graft tissue repair.


RESULTS
The MSC isolated from circulation exhibited multipotential for differentiation in culture, developing into various lineages including osteoblasts, lipocytes, chondrocytes, myotubes, and fibroblasts. Intravenous engraftment of the -labeled cells into recipients of heart transplant resulted in migration of the beta-gal+ cells into the lesions of chronic rejection in the cardiac grafts and homing of the cells to the bone marrow. The majority of beta-gal+ cells present in the allografts exhibited fibroblast phenotypes, and a small number of the cells expressed desmin, indicative of myocyte differentiation.


CONCLUSIONS
MSC vigorously migrated into the site of allograft rejection. This data suggests that they may be attracted to this site to actively participate in tissue repair during chronic rejection. In addition, given the robust migration, the inhibition of MSC differentiation toward fibroblast progeny and induction toward the myocyte lineage may serve as a new strategy for treatment of chronic rejection and allograft tissue repair.
Wu
Gordon D
GD
Department of Cardiothoracic Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. gdw@.usc.edu.
Nolta
Jan A
JA
Jin
Yang-Sun
YS
Barr
Mark L
ML
Yu
Hong
H
Starnes
Vaughn A
VA
Cramer
Donald V
DV
D000818:Animals; D001773:Blood Cells / Q000473:pathology; D001853:Bone Marrow / Q000473:pathology; D002454:Cell Differentiation; D002460:Cell Line; D002465:Cell Movement; D017690:Cell Transplantation; D002908:Chronic Disease; D003094:Collagen; D004338:Drug Combinations; D005821:Genetic Techniques; D006084:Graft Rejection / Q000473:pathology / Q000503:physiopathology*; D006085:Graft Survival; D016027:Heart Transplantation; D007763:Lac Operon; D007797:Laminin; D008648:Mesoderm / Q000166:cytology*; D009206:Myocardium / Q000473:pathology; D016133:Polymerase Chain Reaction; D011509:Proteoglycans; D051381:Rats; D011917:Rats, Inbred Lew; D013234:Stem Cells / Q000473:pathology / Q000502:physiology*; D017154:Stromal Cells / Q000473:pathology / Q000502:physiology; D013997:Time Factors; D014184:Transplantation, Homologous; D014945:Wound Healing / Q000502:physiology
D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; C059485:matrigel; D003094:Collagen