Immune tolerance induction using fetal directed placental injection in rodent models: a murine model.
OBJECTIVES:Induction of the immune response is a major problem in replacement therapies for inherited protein deficiencies. Tolerance created in utero can facilitate postnatal treatment. In this study, we aimed to induce immune tolerance towards a foreign protein with early gestational cell transpla...
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doaj-05ac6715862c454fac258723a5fdb5642020-11-25T01:56:28ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01104e012371210.1371/journal.pone.0123712Immune tolerance induction using fetal directed placental injection in rodent models: a murine model.Kei TakahashiMasayuki EndoTakekazu MiyoshiMitsuhiro TsuritaniYukiko ShimazuHiroshi HosodaKotaro SagaKatsuto TamaiAlan W FlakeJun YoshimatsuTadashi KimuraOBJECTIVES:Induction of the immune response is a major problem in replacement therapies for inherited protein deficiencies. Tolerance created in utero can facilitate postnatal treatment. In this study, we aimed to induce immune tolerance towards a foreign protein with early gestational cell transplantation into the chorionic villi under ultrasound guidance in the murine model. METHODS:Pregnant C57BL/6 (B6) mice on day 10 of gestation were anesthetized and imaged by high resolution ultrasound. Murine embryos and their placenta were positioned to get a clear view in B-mode with power mode of the labyrinth, which is the equivalent of chorionic villi in the human. Bone marrow cells (BMCs) from B6-Green Fluorescence Protein (B6GFP) transgenic mice were injected into the fetal side of the placenta which includes the labyrinth with glass microcapillary pipettes. Each fetal mouse received 2 x 105 viable GFP-BMCs. After birth, we evaluated the humoral and cell-mediated immune response against GFP. RESULTS:Bone marrow transfer into fetal side of placenta efficiently distributed donor cells to the fetal mice. The survival rate of this procedure was 13.5%(5 out of 37). Successful engraftment of the B6-GFP donor skin grafts was observed in all recipient (5 out of 5) mice 6 weeks after birth. Induction of anti-GFP antibodies was completely inhibited. Cytotoxic immune reactivity of thymic cells against cells harboring GFP was suppressed by ELISPOT assay. CONCLUSIONS:In this study, we utilized early gestational placental injection targeting the murine fetus, to transfer donor cells carrying a foreign protein into the fetal circulation. This approach is sufficient to induce both humoral and cell-mediated immune tolerance against the foreign protein.http://europepmc.org/articles/PMC4395343?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Kei Takahashi Masayuki Endo Takekazu Miyoshi Mitsuhiro Tsuritani Yukiko Shimazu Hiroshi Hosoda Kotaro Saga Katsuto Tamai Alan W Flake Jun Yoshimatsu Tadashi Kimura |
spellingShingle |
Kei Takahashi Masayuki Endo Takekazu Miyoshi Mitsuhiro Tsuritani Yukiko Shimazu Hiroshi Hosoda Kotaro Saga Katsuto Tamai Alan W Flake Jun Yoshimatsu Tadashi Kimura Immune tolerance induction using fetal directed placental injection in rodent models: a murine model. PLoS ONE |
author_facet |
Kei Takahashi Masayuki Endo Takekazu Miyoshi Mitsuhiro Tsuritani Yukiko Shimazu Hiroshi Hosoda Kotaro Saga Katsuto Tamai Alan W Flake Jun Yoshimatsu Tadashi Kimura |
author_sort |
Kei Takahashi |
title |
Immune tolerance induction using fetal directed placental injection in rodent models: a murine model. |
title_short |
Immune tolerance induction using fetal directed placental injection in rodent models: a murine model. |
title_full |
Immune tolerance induction using fetal directed placental injection in rodent models: a murine model. |
title_fullStr |
Immune tolerance induction using fetal directed placental injection in rodent models: a murine model. |
title_full_unstemmed |
Immune tolerance induction using fetal directed placental injection in rodent models: a murine model. |
title_sort |
immune tolerance induction using fetal directed placental injection in rodent models: a murine model. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2015-01-01 |
description |
OBJECTIVES:Induction of the immune response is a major problem in replacement therapies for inherited protein deficiencies. Tolerance created in utero can facilitate postnatal treatment. In this study, we aimed to induce immune tolerance towards a foreign protein with early gestational cell transplantation into the chorionic villi under ultrasound guidance in the murine model. METHODS:Pregnant C57BL/6 (B6) mice on day 10 of gestation were anesthetized and imaged by high resolution ultrasound. Murine embryos and their placenta were positioned to get a clear view in B-mode with power mode of the labyrinth, which is the equivalent of chorionic villi in the human. Bone marrow cells (BMCs) from B6-Green Fluorescence Protein (B6GFP) transgenic mice were injected into the fetal side of the placenta which includes the labyrinth with glass microcapillary pipettes. Each fetal mouse received 2 x 105 viable GFP-BMCs. After birth, we evaluated the humoral and cell-mediated immune response against GFP. RESULTS:Bone marrow transfer into fetal side of placenta efficiently distributed donor cells to the fetal mice. The survival rate of this procedure was 13.5%(5 out of 37). Successful engraftment of the B6-GFP donor skin grafts was observed in all recipient (5 out of 5) mice 6 weeks after birth. Induction of anti-GFP antibodies was completely inhibited. Cytotoxic immune reactivity of thymic cells against cells harboring GFP was suppressed by ELISPOT assay. CONCLUSIONS:In this study, we utilized early gestational placental injection targeting the murine fetus, to transfer donor cells carrying a foreign protein into the fetal circulation. This approach is sufficient to induce both humoral and cell-mediated immune tolerance against the foreign protein. |
url |
http://europepmc.org/articles/PMC4395343?pdf=render |
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