Chimeric Allografts Induced by Short-Term Treatment With Stem Cell–Mobilizing Agents Result in Long-Term Kidney Transplant Survival Without Immunosuppression: A Study in Rats

X. Hu, T. Okabayashi, A. M. Cameron, Y. Wang, M. Hisada, J. Li, L. C. Raccusen, Q. Zheng, R. A. Montgomery, G. M. Williams, Z. Sun

Research output: Contribution to journalArticlepeer-review

Abstract

Transplant tolerance allowing the elimination of lifelong immunosuppression has been the goal of research for 60 years. The induction of mixed chimerism has shown promise and has been extended successfully to large animals and to the clinic; however, it remains cumbersome and requires heavy early immunosuppression. In this study, we reported that four injections of AMD3100, a CXCR4 antagonist, plus eight injections of low-dose FK506 (0.05 mg/kg per day) in the first week after kidney transplantation extended survival, but death from renal failure occurred at 30–90 days. Repeating the same course of AMD3100 and FK506 at 1, 2 and 3 mo after transplant resulted in 92% allograft acceptance (n = 12) at 7 mo, normal kidney function and histology with no further treatment. Transplant acceptance was associated with the influx of host stem cells, resulting in a hybrid kidney and a modulated host immune response. Confirmation of these results could initiate a paradigm shift in posttransplant therapy.

Original languageEnglish (US)
Pages (from-to)2055-2065
Number of pages11
JournalAmerican Journal of Transplantation
Volume16
Issue number7
DOIs
StatePublished - Jul 1 2016

Keywords

  • basic (laboratory) research/science
  • kidney transplantation/nephrology
  • organ acceptance
  • pathology/histopathology
  • regenerative medicine
  • rejection: acute
  • stem cells
  • tissue injury and repair
  • tolerance
  • translational research/science

ASJC Scopus subject areas

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)

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