Apheresis of Deceased Donors: A New Source of Mobilized Peripheral Blood Hematopoietic Stem Cells for Transplant Tolerance
1Pathology and Lab Medicine, UCLA, Los Angeles, CA, 2One Legacy, Los Angeles, CA, 3Microbiology, Immunology and Molecular Genetics, UCLA, Los Angeles, CA, 4LifeStream Blood Bank, San Bernadino, CA, 5Surgery, UCLA, Los Angeles, CA, 6Medicine, UCLA, Los Angeles, CA, 7Urology, UCLA, Los Angeles, CA
Meeting: 2022 American Transplant Congress
Abstract number: 1291
Keywords: Inflammation, Leukocytes, Stem cells, 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: Solid organ transplantation is the therapy of choice for many patients with end-stage organ failure, but recipients must remain on lifelong immune suppression, leaving them susceptible to infections and cancer. The study of transplant tolerance to prolong graft survival in the absence of immunosuppression has been restricted to recipients of living donor allografts, yet deceased donors significantly outnumber living donors. In this study, we investigated the potential to obtain a reliable source of hematopoietic stem cells (HSCs) via mobilization into the peripheral blood for apheresis collection, towards the goal of enabling clinical trials of tolerance following deceased donor transplantation. Mobilization of HSCs from the bone marrow to the peripheral blood could allow PB-HSCs to be obtained from deceased donors, and be used to induce tolerance in the kidney recipient; however, a major concern is the well-known concomitant mobilization of immune cells into the liver. As 95% of transplanted livers are obtained from an already limited pool of deceased donors, the field cannot afford any further reduction in available organs.
*Methods: We mobilized HSCs to the peripheral blood using a protocol of two doses of GCSF and one dose of Plerixafor followed by collection of mobilized cells via apheresis in three deceased donors. Physiologic, laboratory and radiographic parameters were monitored throughout the procedure. Longitudinal biopsies were obtained to assess the potential for ectopic mobilization into the liver.
*Results: Physiologic, laboratory and radiographic parameters remained stable throughout the procedure. The use of both agents led to successful mobilization of peripheral blood CD34+ cells, sufficient for most transplant tolerance protocols. Increased immune cell trafficking into the liver was not observed, and apheresis of mobilized cells resulted in a uniform decrease in all liver leukocyte subsets.
*Conclusions: HSCs can be mobilized and collected from the peripheral blood of brain-dead donors. This new approach may facilitate dissemination of immune tolerance trials beyond living donor kidney transplantation to deceased donor transplantation, without sacrificing the liver’s transplantability. As most transplant procedures are from deceased donors, recipients of other solid organs as well as vascularized composite allografts would therefore become candidates for immune tolerance trials.
To cite this abstract in AMA style:
Sosa RA, Mone T, Naini BV, Kohn DB, Reed EF, Wheeler K, Campo-Fernandez B, Davila A, Chaffin DJ, DiNorcia J, Kaldas FM, Cohen A, Lum E, Veale JL, Kogut NM. Apheresis of Deceased Donors: A New Source of Mobilized Peripheral Blood Hematopoietic Stem Cells for Transplant Tolerance [abstract]. Am J Transplant. 2022; 22 (suppl 3). https://atcmeetingabstracts.com/abstract/apheresis-of-deceased-donors-a-new-source-of-mobilized-peripheral-blood-hematopoietic-stem-cells-for-transplant-tolerance/. Accessed December 2, 2024.« Back to 2022 American Transplant Congress