title: Allogeneic bone marrow-derived flk-1+Sca-1- mesenchymal stem cells leads to stable mixed chimerism and donor-specific tolerance.
abstract: 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.
authors.affiliation: Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, PR China.
authors.forename: Weimin
authors.initials: W
authors.lastname: Deng
authors.forename: Qin
authors.initials: Q
authors.lastname: Han
authors.forename: Lianming
authors.initials: L
authors.lastname: Liao
authors.forename: Changhong
authors.initials: C
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Ge
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Zhao
authors.forename: Shengguo
authors.initials: S
authors.lastname: You
authors.forename: Hongye
authors.initials: H
authors.lastname: Deng
authors.forename: Robert C H
authors.initials: RC
authors.lastname: Zhao
mesh_terms: 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*
chemical_list: D000950:Antigens, Ly; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; D040301:Vascular Endothelial Growth Factor Receptor-2