Impacts of Amnion-Derived Multi-Potent Progenitor (AMP) Cells on Mixed Chimerism Induction in Humanized Mouse

Presentation Number: LB MON 82
Date of Presentation: April 3rd, 2017

Andrea Vecchione*1, Megan Sykes2 and Haowei Li2
1City of Hope, Duarte, CA, 2Columbia University Medical Center, New York, NY

Abstract

Impact of Amnion-Derived Multipotent Progenitor (AMP) Cells on Mixed Chimerism Induction in Humanized Mice

Andrea Vecchione, MSc1, 2, Richard A. Banas, MSc3 and Megan Sykes, MD 1, Hao Wei Li, PhD1

1. Department of Medicine, Columbia University Medical Center, New York, United States of America; 2. Department of Diabetes Immunology, City of Hope, Duarte, United States of America; 3. Noveome Biotherapeutics, Inc., Pittsburgh, PA, United States of America

ABSTRACT

Allograft rejection represents one of the major problems for organ transplantation. Long-term administration of immunosuppressive drugs have been extensively used to control rejection, but their use is associated with many negative side effects1. It has been shown that when recipient and donor hematopoietic stem cell populations coexist, a condition known as mixed chimerism, tolerance induction of donor allografts results2. Although transiently established mixed chimerism in non-human primates leads to toleration of transplanted kidneys, durable mixed chimerism is necessary for acceptance of other organ types3. Human Amnion-derived Multipotent Progenitor (AMP) cells have been shown in vitro to possess immunomodulatory properties, such as inhibition of T cell proliferation, suppression of dendritic cell maturation, and induction of regulatory cytokines by immune effector cells4,5. In an in vivo model, AMP cells suppressed mouse allogeneic Mixed Lymphocyte Reactions (MLRs) and induced tolerance of donor BALC/c mouse skin grafts in recipient C5BL/6 mice via mixed chimerism induction6. It is hypothesized that AMP cells may potentially facilitate induction of durable mixed chimerism in humans. The present research focused on: (i) the ability of AMP cells co-injected with allogeneic hematopoietic stem cells to facilitate induction of durable mixed chimerism in a humanized mouse model; (ii) evaluate how many AMP cells are necessary to induce mixed chimerism (dose); and (iii) to understand what AMP cell-related immunomodulatory mechanisms might be involved. The results suggest that AMP cell-mediated suppression involved T regulatory cell differentiation, increased expression of CD3 and CD8 on T cells, and increased expression of CD81 (TAPA-1) on B cells. Interestingly, traditional immunosuppressive molecules HLA-G, PD-L1 and PD-L2, which are expressed on activated AMP cells4, did not have a role in in vitro suppression. Finally, these studies failed to show a significant effect of AMP cell treatment on induction of durable mixed chimerism using the humanized mouse model and did not significantly improve consistent chimerism compared to control animals that did not receive AMP cells. It was observed that mice receiving the low dose of AMP cells (1.25x106) had a better reconstitution of HLA-A2- recipient cells compared to groups receiving higher doses of AMP cells and untreated controls.

 

Nothing to Disclose: AV, MS, HL