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https://doi.org/10.1096/fj.202002185RR
Title: | Maternal microchimerism and cell-mediated immune-modulation enhance engraftment following semi-allogenic intrauterine transplantation | Authors: | Kandasamy, Karthikeyan Tan, Lay Geok Johana, Nuryanti B Tan, Yi Wan Foo, Wanling Yeo, Julie SL Ravikumar, Vikashini Ginhoux, Florent Choolani, Mahesh Chan, Jerry KY Mattar, Citra NZ |
Keywords: | Science & Technology Life Sciences & Biomedicine Biochemistry & Molecular Biology Biology Cell Biology Life Sciences & Biomedicine - Other Topics bone marrow cells fetal therapy hematopoietic stem and progenitor cells intrauterine transplantation maternal donor cells paternal donor cells semi‐ allogenic donor cells BONE-MARROW-TRANSPLANTATION HEMATOPOIETIC STEM-CELLS REGULATORY T-CELLS PRENATAL TOLERANCE INDUCTION VERSUS-HOST-DISEASE CANINE MODEL CHIMERISM DELETION ANTIGENS MHC |
Issue Date: | Mar-2021 | Publisher: | WILEY | Citation: | Kandasamy, Karthikeyan, Tan, Lay Geok, Johana, Nuryanti B, Tan, Yi Wan, Foo, Wanling, Yeo, Julie SL, Ravikumar, Vikashini, Ginhoux, Florent, Choolani, Mahesh, Chan, Jerry KY, Mattar, Citra NZ (2021-03). Maternal microchimerism and cell-mediated immune-modulation enhance engraftment following semi-allogenic intrauterine transplantation. FASEB JOURNAL 35 (3). ScholarBank@NUS Repository. https://doi.org/10.1096/fj.202002185RR | Abstract: | Successful intrauterine hematopoietic cell transplantation (IUT) for congenital hemoglobinopathies is hampered by maternal alloresponsiveness. We investigate these interactions in semi-allogenic murine IUT. E14 fetuses (B6 females × BALB/c males) were each treated with 5E+6 maternal (B6) or paternal (BALB/c) bone marrow cells and serially monitored for chimerism (>1% engraftment), trafficked maternal immune cells, and immune responsiveness to donor cells. A total of 41.0% of maternal IUT recipients (mIUT) were chimeras (mean donor chimerism 3.0 ± 1.3%) versus 75.0% of paternal IUT recipients (pIUT, 3.6 ± 1.1%). Chimeras showed higher maternal microchimerism of CD4, CD8, and CD19 than non-chimeras. These maternal cells showed minimal responsiveness to B6 or BALB/c stimulation. To interrogate tolerance, mIUT were injected postnatally with 5E+6 B6 cells/pup; pIUT received BALB/c cells. IUT-treated pups showed no changes in trafficked maternal or fetal immune cell levels compared to controls. Donor-specific IgM and IgG were expressed by 1%-3% of recipients. mIUT splenocytes showed greater proliferation of regulatory T cells (Treg) upon BALB/c stimulation, while B6 stimulation upregulated the pro-inflammatory cytokines more than BALB/c. pIUT splenocytes produced identical Treg and cytokine responses to BALB/c and B6 cells, with higher Treg activity and lower pro-inflammatory cytokine expression upon exposure to BALB/c. In contrast, naïve fetal splenocytes demonstrated greater alloresponsiveness to BALB/c compared to B6 cells. Thus pIUT, associated with increased maternal cell trafficking, modulates fetal Treg, and cytokine responsiveness to donor cells more efficiently than mIUT, resulting in improved engraftment. Paternal donor cells may be considered alternatively to maternal donor cells for intrauterine and postnatal transplantation to induce tolerance and maintain engraftment. | Source Title: | FASEB JOURNAL | URI: | https://scholarbank.nus.edu.sg/handle/10635/245757 | ISSN: | 0892-6638 1530-6860 |
DOI: | 10.1096/fj.202002185RR |
Appears in Collections: | Staff Publications Elements |
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