Potential of Membranes Surrounding the Fetus as Immunoprotective Cell-Carriers for Allogeneic Transplantations
Background. Membranes surrounding the fetus play a crucial role in providing a physical and immunological barrier between a semiallogeneic fetus and mother during pregnancy. In this study, we tested whether cotransplantation of fetal membranes (FMs) and allogeneic donor cells would improve the reten...
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2019-06-01
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doaj-65b0246cd6dd453c85c76e86f753eff82020-11-25T03:55:16ZengWolters KluwerTransplantation Direct2373-87312019-06-0156e46010.1097/TXD.0000000000000901201906000-00008Potential of Membranes Surrounding the Fetus as Immunoprotective Cell-Carriers for Allogeneic TransplantationsPadma Priya Togarrati, PhD0Nuntana Dinglasan, BS1Elizabeth Yee, BS2John W. Heitman, BS3Rachael P. Jackman, PhD4Mark Geisberg, PhD5Philip J. Norris, MD6Alicia Bárcena, PhD7Marcus O. Muench, PhD81Vitalant Research Institute, San Francisco, CA.1Vitalant Research Institute, San Francisco, CA.1Vitalant Research Institute, San Francisco, CA.1Vitalant Research Institute, San Francisco, CA.1Vitalant Research Institute, San Francisco, CA.3Silver Lake Research Corporation, Azusa, CA.1Vitalant Research Institute, San Francisco, CA.4The Ely and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, CA.1Vitalant Research Institute, San Francisco, CA.Background. Membranes surrounding the fetus play a crucial role in providing a physical and immunological barrier between a semiallogeneic fetus and mother during pregnancy. In this study, we tested whether cotransplantation of fetal membranes (FMs) and allogeneic donor cells would improve the retention and function of allografts in mice. Methods. Intact and enzyme-digested membranes obtained from E18-E19 pregnant mice were subcutaneously cotransplanted with 10F7MN hybridoma cells that are of BALB/cByJ (Balb) origin and secrete anti-human CD235a antibody. Cells were transplanted into C57BL/6J (B6, allogeneic), Balb (syngeneic), and FVB/NJ (third-party) mice. Serum was collected after 1 and 3 weeks of cell transplantation and tested using flow cytometry for the presence of anti-human CD235a antibody. Immunosuppressive functions of membranes were further investigated by analyzing the cytokine profile of supernatants collected from allo-reactive mixed lymphocyte reactions (MLRs) using a multiplex cytokine assay. Results. B6 mice transplanted with 10F7MN cells along with membranes syngeneic to the host had significantly higher levels of CD235a antibody when compared to B6 mice that received cells without membranes, allogenic membranes, or third-party membranes. Syngeneic membranes significantly inhibited T-cell proliferation in the presence of allogeneic stimuli and suppressed the release of Th1-cytokines such as IFNγ, TNFα, and IL-2 in MLRs. Additionally, increases in the levels of Th2-cytokines were found in MLRs containing membrane-derived cells. Conclusions. Our study highlights the potential use of syngeneic FMs to act as potent cell-carriers that could improve graft retention as well as graft-specific immunoprotection during allograft transplantation.http://journals.lww.com/transplantationdirect/fulltext/10.1097/TXD.0000000000000901 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Padma Priya Togarrati, PhD Nuntana Dinglasan, BS Elizabeth Yee, BS John W. Heitman, BS Rachael P. Jackman, PhD Mark Geisberg, PhD Philip J. Norris, MD Alicia Bárcena, PhD Marcus O. Muench, PhD |
spellingShingle |
Padma Priya Togarrati, PhD Nuntana Dinglasan, BS Elizabeth Yee, BS John W. Heitman, BS Rachael P. Jackman, PhD Mark Geisberg, PhD Philip J. Norris, MD Alicia Bárcena, PhD Marcus O. Muench, PhD Potential of Membranes Surrounding the Fetus as Immunoprotective Cell-Carriers for Allogeneic Transplantations Transplantation Direct |
author_facet |
Padma Priya Togarrati, PhD Nuntana Dinglasan, BS Elizabeth Yee, BS John W. Heitman, BS Rachael P. Jackman, PhD Mark Geisberg, PhD Philip J. Norris, MD Alicia Bárcena, PhD Marcus O. Muench, PhD |
author_sort |
Padma Priya Togarrati, PhD |
title |
Potential of Membranes Surrounding the Fetus as Immunoprotective Cell-Carriers for Allogeneic Transplantations |
title_short |
Potential of Membranes Surrounding the Fetus as Immunoprotective Cell-Carriers for Allogeneic Transplantations |
title_full |
Potential of Membranes Surrounding the Fetus as Immunoprotective Cell-Carriers for Allogeneic Transplantations |
title_fullStr |
Potential of Membranes Surrounding the Fetus as Immunoprotective Cell-Carriers for Allogeneic Transplantations |
title_full_unstemmed |
Potential of Membranes Surrounding the Fetus as Immunoprotective Cell-Carriers for Allogeneic Transplantations |
title_sort |
potential of membranes surrounding the fetus as immunoprotective cell-carriers for allogeneic transplantations |
publisher |
Wolters Kluwer |
series |
Transplantation Direct |
issn |
2373-8731 |
publishDate |
2019-06-01 |
description |
Background. Membranes surrounding the fetus play a crucial role in providing a physical and immunological barrier between a semiallogeneic fetus and mother during pregnancy. In this study, we tested whether cotransplantation of fetal membranes (FMs) and allogeneic donor cells would improve the retention and function of allografts in mice.
Methods. Intact and enzyme-digested membranes obtained from E18-E19 pregnant mice were subcutaneously cotransplanted with 10F7MN hybridoma cells that are of BALB/cByJ (Balb) origin and secrete anti-human CD235a antibody. Cells were transplanted into C57BL/6J (B6, allogeneic), Balb (syngeneic), and FVB/NJ (third-party) mice. Serum was collected after 1 and 3 weeks of cell transplantation and tested using flow cytometry for the presence of anti-human CD235a antibody. Immunosuppressive functions of membranes were further investigated by analyzing the cytokine profile of supernatants collected from allo-reactive mixed lymphocyte reactions (MLRs) using a multiplex cytokine assay.
Results. B6 mice transplanted with 10F7MN cells along with membranes syngeneic to the host had significantly higher levels of CD235a antibody when compared to B6 mice that received cells without membranes, allogenic membranes, or third-party membranes. Syngeneic membranes significantly inhibited T-cell proliferation in the presence of allogeneic stimuli and suppressed the release of Th1-cytokines such as IFNγ, TNFα, and IL-2 in MLRs. Additionally, increases in the levels of Th2-cytokines were found in MLRs containing membrane-derived cells.
Conclusions. Our study highlights the potential use of syngeneic FMs to act as potent cell-carriers that could improve graft retention as well as graft-specific immunoprotection during allograft transplantation. |
url |
http://journals.lww.com/transplantationdirect/fulltext/10.1097/TXD.0000000000000901 |
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