Induction therapy with autologous mesenchymal stem cells in living-related kidney transplants: A randomized controlled trial

Jianming Tan, Weizhen Wu, Xiumin Xu, Lianming Liao, Feng Zheng, Shari Messinger, Xinhui Sun, Jin Chen, Shunliang Yang, Jinquan Cai, Xia Gao, Antonello Pileggi, Camillo Ricordi

Research output: Contribution to journalArticle

340 Scopus citations

Abstract

Context: 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. Design, Setting, and Patients: 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. Intervention: Patients were inoculated with marrow-derived autologous MSC (1-2 × 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 antibodyplusstandard-dose CNIs. Main OutcomeMeasures: 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) Conclusion 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. Trial Registration clinicaltrials.gov Identifier: NCT00658073

Original languageEnglish (US)
Pages (from-to)1169-1177
Number of pages9
JournalJAMA - Journal of the American Medical Association
Volume307
Issue number11
DOIs
StatePublished - Mar 21 2012

ASJC Scopus subject areas

  • Medicine(all)

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