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Immune tolerance induction using fetal directed placental injection in rodent models: a murine model.
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- Additional Information
- Source:
Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE
- Publication Information:
Original Publication: San Francisco, CA : Public Library of Science
- Subject Terms:
- Abstract:
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.
- References:
Br Med Bull. 1988 Oct;44(4):1037-51. (PMID: 3076825)
Circulation. 2000 Jan 18;101(2):178-84. (PMID: 10637206)
Nature. 1953 Oct 3;172(4379):603-6. (PMID: 13099277)
Physiology (Bethesda). 2005 Jun;20:180-93. (PMID: 15888575)
Exp Hematol. 2006 Sep;34(9):1278-87. (PMID: 16939821)
Stem Cells. 2006 Oct;24(10):2299-308. (PMID: 16794262)
Blood. 2006 Dec 15;108(13):4268-74. (PMID: 16954501)
Am J Pathol. 2008 Sep;173(3):803-14. (PMID: 18688022)
Blood. 2011 Jan 20;117(3):1053-60. (PMID: 21088133)
Adv Nutr. 2011 Sep;2(5):377-95. (PMID: 22332080)
Clin Perinatol. 2012 Jun;39(2):301-10. (PMID: 22682381)
Nat Rev Genet. 2001 Jul;2(7):538-48. (PMID: 11433360)
Proc Natl Acad Sci U S A. 1979 Nov;76(11):5736-40. (PMID: 42904)
J Immunol. 2003 Sep 15;171(6):3270-7. (PMID: 12960357)
Mol Ther. 2002 May;5(5 Pt 1):501-8. (PMID: 11991740)
Best Pract Res Clin Obstet Gynaecol. 2012 Oct;26(5):683-95. (PMID: 22809469)
Fetal Diagn Ther. 1998 Jul-Aug;13(4):216-22. (PMID: 9784641)
- Accession Number:
147336-22-9 (Green Fluorescent Proteins)
- Publication Date:
Date Created: 20150416 Date Completed: 20160426 Latest Revision: 20190223
- Publication Date:
20221213
- Accession Number:
PMC4395343
- Accession Number:
10.1371/journal.pone.0123712
- Accession Number:
25876079
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