title: Donor-derived mesenchymal stem cells combined with low-dose tacrolimus prevent acute rejection after renal transplantation:  a clinical pilot study.
abstract: BACKGROUND
  The deleterious side effects of calcineurin inhibitors have impaired long-term survival after renal allograft. New immunotherapy regimens that minimize or even eliminate calcineurin inhibitors are required to improve transplantation outcome. Mesenchymal stem cells (MSCs) represent a unique cell population with immunosuppressive function and prolong allograft survival in experimental organ transplant models.
  
  
  METHODS
  In this pilot study, donor-derived bone marrow MSCs combined with a sparing dose of tacrolimus (50% of standard dose) were administered to six de novo living-related kidney transplant recipients. Six other patients who received a standard dose of tacrolimus were enrolled as a control. The safety of MSC infusion, acute rejection, graft function, and patient and graft survival within 12 months after kidney transplantation were observed. The immune profiles were analyzed at different time points after transplantation.
  
  
  RESULTS
  None of the MSC recipients experienced immediate or long-term toxic side effects associated with MSC infusion. The tacrolimus dose (0.045±0.002 mg/kg) in the MSC group was significantly reduced compared with the control group (0.077±0.005 mg/kg). One acute rejection occurred only in the control group. All patients survived with stable renal function at month 12 and no chimerism was detectable at month 3. Patients in the MSC group showed significantly higher B-cell levels than the control group at month 3.
  
  
  CONCLUSIONS
  These preliminary data suggest that the use of MSCs could provide potential benefits in renal transplantation by reducing the dosage of conventional immunosuppressive drug that is required to maintain long-term graft survival and function.
authors.affiliation: Center for Stem Cell Biology and Tissue Engineering, SunYat-sen University, 74#, Zhongshan 2 Road, Guangzhou, Guangdong, China, 510080.
authors.forename: Yanwen
authors.initials: Y
authors.lastname: Peng
authors.forename: Ming
authors.initials: M
authors.lastname: Ke
authors.forename: Lu
authors.initials: L
authors.lastname: Xu
authors.forename: Longshan
authors.initials: L
authors.lastname: Liu
authors.forename: Xiaoyong
authors.initials: X
authors.lastname: Chen
authors.forename: Wenjie
authors.initials: W
authors.lastname: Xia
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Li
authors.forename: Zhen
authors.initials: Z
authors.lastname: Chen
authors.forename: Junjie
authors.initials: J
authors.lastname: Ma
authors.forename: Dehuai
authors.initials: D
authors.lastname: Liao
authors.forename: Guanghui
authors.initials: G
authors.lastname: Li
authors.forename: Jiali
authors.initials: J
authors.lastname: Fang
authors.forename: Guanghui
authors.initials: G
authors.lastname: Pan
authors.forename: Andy Peng
authors.initials: AP
authors.lastname: Xiang
mesh_terms: D000208:Acute Disease; D000328:Adult; D016207:Cytokines / Q000032:analysis; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D016030:Kidney Transplantation / Q000009:adverse effects*; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D008875:Middle Aged; D010865:Pilot Projects; D016559:Tacrolimus / Q000008:administration & dosage*; D014019:Tissue Donors; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000032:analysis
chemical_list: D016207:Cytokines; D007166:Immunosuppressive Agents; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D016559:Tacrolimus