ATC Abstracts

American Transplant Congress abstracts

  • Home
  • Meetings Archive
    • 2022 American Transplant Congress
    • 2021 American Transplant Congress
    • 2020 American Transplant Congress
    • 2019 American Transplant Congress
    • 2018 American Transplant Congress
    • 2017 American Transplant Congress
    • 2016 American Transplant Congress
    • 2015 American Transplant Congress
    • 2013 American Transplant Congress
  • Keyword Index
  • Resources
    • 2021 Resources
    • 2016 Resources
      • 2016 Welcome Letter
      • ATC 2016 Program Planning Committees
      • ASTS Council 2015-2016
      • AST Board of Directors 2015-2016
    • 2015 Resources
      • 2015 Welcome Letter
      • ATC 2015 Program Planning Committees
      • ASTS Council 2014-2015
      • AST Board of Directors 2014-2015
      • 2015 Conference Schedule
  • Search

Tolerance of Allogeneic Kidneys with Durable (>200 Days) Multilineage Chimerism and Bone Marrow Engraftment in Cynomolgus Macaques

Y. Tomori1, Y. Hisadome1, D. Eisenson1, K. Takeuchi1, K. Okubo1, C. Huang2, D. Sachs1, M. Sykes1, K. Yamada1

1CCTI/Surgery and Medicine, Columbia University, New York, NY, 2University of Colorado Denver, Aurora, CO

Meeting: 2022 American Transplant Congress

Abstract number: 1279

Keywords: Kidney transplantation, Mixed chimerism, Preclinical trails, Tolerance

Topic: Basic Science » Basic Science » 12 - Immunosuppression & Tolerance: Preclinical & Translational Studies

Session Information

Session Name: Immunosuppression & Tolerance: Preclinical & Translational Studies

Session Type: Poster Abstract

Date: Monday, June 6, 2022

Session Time: 7:00pm-8:00pm

 Presentation Time: 7:00pm-8:00pm

Location: Hynes Halls C & D

*Purpose: We have previously reported that a regimen including anti-CD3 immunotoxin, 45 days of cyclosporine, and pre-transplant total body irradiation (TBI) promoted tolerance of kidney allografts with transient chimerism in non-human primates. Donor islets were also tolerated when transplanted in composite islet-kidney (IK) grafts. However, data from a rodent model demonstrated that durable chimerism may be required to reverse the autoimmunity responsible for type-1 diabetes (T1D). As the first step toward our goal of curing T1D and diabetic nephropathy by transplantation of IKs, we aimed to develop a clinically applicable protocol to induce tolerance of allogeneic kidneys with >6 months durable chimerism in NHPs.

*Methods: Cynomolgus macaques received mobilized peripheral blood hematopoietic stem cell transplantation (PBHSCTx) on Day 0 followed by donor kidney Tx (DKTx) on Day 42 from one haplotype-mismatched donors. Recipients in Group 1 (n=5) received PBHSCTx that contained 3.7-20×10^7 cells/kg recipient body weight (bwt) CD34+ cells. Recipients in Group 2 (n=4) received PBHSCTx containing a lower dose of CD34+ cells (2×10^7 cells/bwt). All recipients received Rituximab, rATG, and 100cGy of TBI before PBHSCTx. Tacrolimus was administered daily starting on Day -1 and was stopped at Day 41. Anti-CD40mAb was administered twice weekly until 30 days after DKTx.

*Results: All animals developed and maintained multilineage chimerism with evidence of bone marrow (BM) engraftment throughout the experimental period. However, animals in Group 1 developed severe GVHD or cytokine storm requiring euthanasia at early time points (Days 33, 43, 45, 55, 92). In contrast, recipients in Group 2 had no evidence of GVHD or cytokine storm, and demonstrated prolonged rejection-free survival (p<0.02). Although one animal was euthanized at Day 78 due to ureteral stent complication and another animal was euthanized at Day 118 due to CMV disease, the other two survived >7 months (218 days [euthanized due to CMV disease] and >246 days which is ongoing [Cre 1.1mg/dL]). In these long-term survivors, we observed (1) donor-specific unresponsiveness in vitro, (2) donor cells in the host thymus, and (3) donor-derived recent thymic emigrants along with multilineage peripheral blood chimerism and BM chimerism >200 days after PBHSCTx, with stable renal allograft function.

*Conclusions: This is the first demonstration of reproducible, long-term (>7 months), multilineage durable chimerism with BM engraftment and kidney graft tolerance in our cynomolgus HSCTx with kidney Tx model. Achieving long-term durable chimerism, which may be necessary to overcome autoimmunity of T1DM, allows us to confidently extend this protocol to composite IK Tx, moving us one step closer to a clinical trial.

  • Tweet
  • Click to email a link to a friend (Opens in new window) Email
  • Click to print (Opens in new window) Print

To cite this abstract in AMA style:

Tomori Y, Hisadome Y, Eisenson D, Takeuchi K, Okubo K, Huang C, Sachs D, Sykes M, Yamada K. Tolerance of Allogeneic Kidneys with Durable (>200 Days) Multilineage Chimerism and Bone Marrow Engraftment in Cynomolgus Macaques [abstract]. Am J Transplant. 2022; 22 (suppl 3). https://atcmeetingabstracts.com/abstract/tolerance-of-allogeneic-kidneys-with-durable-200-days-multilineage-chimerism-and-bone-marrow-engraftment-in-cynomolgus-macaques/. Accessed May 28, 2025.

« Back to 2022 American Transplant Congress

Visit Our Partner Sites

American Transplant Congress (ATC)

Visit the official site for the American Transplant Congress »

American Journal of Transplantation

The official publication for the American Society of Transplantation (AST) and the American Society of Transplant Surgeons (ASTS) »

American Society of Transplantation (AST)

An organization of more than 3000 professionals dedicated to advancing the field of transplantation. »

American Society of Transplant Surgeons (ASTS)

The society represents approximately 1,800 professionals dedicated to excellence in transplantation surgery. »

Copyright © 2013-2025 by American Society of Transplantation and the American Society of Transplant Surgeons. All rights reserved.

Privacy Policy | Terms of Use | Cookie Preferences