Mesenchymal Stem Cells Suppress Chronic Rejection in Heterotopic Small Intestine Transplant Rat Models Via Inhibition of CD68, Transforming Growth Factor- β1, and Platelet-Derived Growth Factor Expression.
OBJECTIVE
Mesenchymal stem cells are easy to obtain and expand, with characteristics of low immunogenicity and strong tissue repair capacity. In this study, our aim was to investigate the role of mesenchymal stem cells in chronic immune rejection of heterotopic small intestine transplant in rats.


METHODS
After successfully constructing a rat chronic immune rejection model of heterotopic small intestine transplant, we infused mesenchymal stem cells into the animal recipients. We observed mesenchymal stem cell location in the recipients, recipient survival, pathology changes, and the expression of CD68, transforming growth factor β1, and platelet-derived growth factor C in the donor intestine.


RESULTS
Mesenchymal stem cells inhibited the lymphocyte proliferation caused by concanavalin A in vitro. After stem cells were infused into recipients, they were mainly located in the donor intestine, as well as in the spleen and thymus. Recovery after transplant and pathology changes of the donor intestine in rats with stem cell infusion were better than in the control group; however, we observed no differences in survival time, accompanied by downregulated expression of CD68, transforming growth factor β1, and platelet-derived growth factor C.


CONCLUSIONS
Mesenchymal stem cells, to a certain extent, could inhibit the process of chronic rejection. The mechanisms may include the inhibited function of these cells on lymphocyte proliferation, reduced infiltration of macrophages, and reduced expression of transforming growth factor β1 and platelet-derived growth factor C.
Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China.
Fuxin
F
Li
Jisen
J
Cao
Zhicheng
Z
Zhao
Chuan
C
Li
Feng
F
Qi
Tong
T
Liu
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism*; D049109:Cell Proliferation; D002478:Cells, Cultured; D002908:Chronic Disease; D018920:Coculture Techniques; D004195:Disease Models, Animal; D015536:Down-Regulation; D006084:Graft Rejection / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D006085:Graft Survival; D007421:Intestine, Small / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000637:transplantation*; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism; D008222:Lymphokines / Q000378:metabolism*; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D015398:Signal Transduction; D013997:Time Factors; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*; D016042:Transplantation, Heterotopic; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D008222:Lymphokines; D010982:Platelet-Derived Growth Factor; D053773:Transforming Growth Factor beta1; C539355:CD68 protein, rat; D000097382:CD68 Molecule; C508962:Tgfb1 protein, rat; C411423:platelet-derived growth factor C