title: Induction therapy with autologous mesenchymal stem cells in living-related kidney transplants: a randomized controlled trial.
abstract: BACKGROUND
  Antibody-based induction therapy plus calcineurin inhibitors (CNIs) reduce acute rejection rates in kidney recipients; however, opportunistic infections and toxic CNI effects remain challenging. Reportedly, mesenchymal stem cells (MSCs) have successfully treated graft-vs-host disease.
  
  
  OBJECTIVE
  To assess autologous MSCs as replacement of antibody induction for patients with end-stage renal disease who undergo ABO-compatible, cross-match-negative kidney transplants from a living-related donor.
  
  
  METHODS
  One hundred fifty-nine patients were enrolled in this single-site, prospective, open-label, randomized study from February 2008-May 2009, when recruitment was completed.
  
  
  METHODS
  Patients were inoculated with marrow-derived autologous MSC (1-2 x 10(6)/kg) at kidney reperfusion and two weeks later. Fifty-three patients received standard-dose and 52 patients received low-dose CNIs (80% of standard); 51 patients in the control group received anti-IL-2 receptor antibody plus standard-dose CNIs.
  
  
  METHODS
  The primary measure was 1-year incidence of acute rejection and renal function (estimated glomerular filtration rate [eGFR]); the secondary measure was patient and graft survival and incidence of adverse events.
  
  
  RESULTS
  Patient and graft survival at 13 to 30 months was similar in all groups. After 6 months, 4 of 53 patients (7.5%) in the autologous MSC plus standard-dose CNI group (95% CI, 0.4%-14.7%; P = .04) and 4 of 52 patients (7.7%) in the low-dose group (95% CI, 0.5%-14.9%; P = .046) compared with 11 of 51 controls (21.6%; 95% CI, 10.5%-32.6%) had biopsy-confirmed acute rejection. None of the patients in either autologous MSC group had glucorticoid-resistant rejection, whereas 4 patients (7.8%) in the control group did (95% CI, 0.6%-15.1%; overall P = .02). Renal function recovered faster among both MSC groups showing increased eGFR levels during the first month after surgery than the control group. Patients receiving standard-dose CNI had a mean difference of 6.2 mL/min per 1.73 m(2) (95% CI, 0.4-11.9; P=.04) and those in the low-dose CNI of 10.0 mL/min per 1.73 m(2) (95% CI, 3.8-16.2; P=.002). Also, during the 1-year follow-up, combined analysis of MSC-treated groups revealed significantly decreased risk of opportunistic infections than the control group (hazard ratio, 0.42; 95% CI, 0.20-0.85, P=.02)
  
  
  CONCLUSIONS
  Among patients undergoing renal transplant, the use of autologous MSCs compared with anti-IL-2 receptor antibody induction therapy resulted in lower incidence of acute rejection, decreased risk of opportunistic infection, and better estimated renal function at 1 year.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00658073.
authors.affiliation: Organ Transplant Institute, Fuzhou General Hospital, Xiamen University and Fujian Key Laboratory of Transplant Biology, Fuzhou, China. tanjm156@yahoo.com.cn
authors.forename: Jianming
authors.initials: J
authors.lastname: Tan
authors.forename: Weizhen
authors.initials: W
authors.lastname: Wu
authors.forename: Xiumin
authors.initials: X
authors.lastname: Xu
authors.forename: Lianming
authors.initials: L
authors.lastname: Liao
authors.forename: Feng
authors.initials: F
authors.lastname: Zheng
authors.forename: Shari
authors.initials: S
authors.lastname: Messinger
authors.forename: Xinhui
authors.initials: X
authors.lastname: Sun
authors.forename: Jin
authors.initials: J
authors.lastname: Chen
authors.forename: Shunliang
authors.initials: S
authors.lastname: Yang
authors.forename: Jinquan
authors.initials: J
authors.lastname: Cai
authors.forename: Xia
authors.initials: X
authors.lastname: Gao
authors.forename: Antonello
authors.initials: A
authors.lastname: Pileggi
authors.forename: Camillo
authors.initials: C
authors.lastname: Ricordi
mesh_terms: D000293:Adolescent; D000328:Adult; D000906:Antibodies / Q000627:therapeutic use; D000917:Antibody Formation; D065095:Calcineurin Inhibitors; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods*; D007668:Kidney / Q000502:physiology; D007676:Kidney Failure, Chronic / Q000601:surgery*; D016030:Kidney Transplantation / Q000276:immunology / Q000379:methods*; D019520:Living Donors; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D008875:Middle Aged; D009894:Opportunistic Infections; D015375:Receptors, Interleukin-2 / Q000037:antagonists & inhibitors; D016019:Survival Analysis; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000906:Antibodies; D065095:Calcineurin Inhibitors; D015375:Receptors, Interleukin-2