Allogeneic bone marrow-derived flk-1+Sca-1- mesenchymal stem cells leads to stable mixed chimerism and donor-specific tolerance.
OBJECTIVE
To investigate the possibility of flk-1+Sca-1- bone marrow-derived mesenchymal stem cells (bMSCs) to induce stable mixed chimerism and donor-specific graft tolerance.


METHODS
Allogeneic flk-1+Sca-1- bMSCs and syngeneic bone marrow (BM) cells were cotransplanted into lethally irradiated (8.5 Gy) recipient mice. FACS was used to analyze the chimerism 150 days later. Donor-type skin transplantation was performed to observe donor-specific immunotolerance in recipient mice. Mixed lymphocyte reaction (MLR) and mitogen proliferative assays were performed to evaluate proliferative response of splenocytes from recipient mice.


RESULTS
More than 5% donor-derived CD3+ cells were detected in splenocytes of recipient mice. Long-term survival of donor-type skin grafts was observed. MLR and mitogen proliferative assays showed that recipient mice had low immunoresponse to donor cells but retained normal ConA-induced proliferative response compared with normal mice.


CONCLUSIONS
Our results show for the first time that induction of stable mixed hematopoietic chimerism can be achieved with allogeneic flk-1+Sca-1- bMSC transplantation, which leads to permanent donor-specific immunotolerance in allogeneic host and results in long-term allogeneic skin graft acceptance.
Deng
Weimin
W
Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, PR China.
Han
Qin
Q
Liao
Lianming
L
Li
Changhong
C
Ge
Wei
W
Zhao
Zhigang
Z
You
Shengguo
S
Deng
Hongye
H
Zhao
Robert C H
RC
D000818:Animals; D000950:Antigens, Ly / Q000032:analysis*; D001854:Bone Marrow Cells / Q000166:cytology*; D005260:Female; D007108:Immune Tolerance; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D008565:Membrane Proteins / Q000032:analysis*; D045164:Mesenchymal Stem Cell Transplantation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016038:Skin Transplantation / Q000276:immunology*; D018183:Transplantation Chimera; D014184:Transplantation, Homologous; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000032:analysis*
D000950:Antigens, Ly; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; D040301:Vascular Endothelial Growth Factor Receptor-2