ArticleThe Journal of clinical investigation2009
Maternal alloantibodies induce a postnatal immune response that limits engraftment following in utero hematopoietic cell transplantation in mice.
Article in The Journal of clinical investigation, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 87 citations in OpenAlex.
- In utero hematopoietic cell transplantation in fetuses with α-thalassemia major: a phase 1 clinical trial.Blood advances · 2026Article
- Cellular trafficking and fate mapping of cells within the nervous system after in utero hematopoietic cell transplantation.Communications biology · 2024Article
- Immune modulation permits tolerance and engraftment in a murine model of late-gestation transplantation.Blood advances · 2024Article
- Preexisting maternal immunity to AAV but not Cas9 impairs in utero gene editing in mice.The Journal of clinical investigation · 2024Article
- Maternal dendritic cells influence fetal allograft response following murine in-utero hematopoietic stem cell transplantation.Stem cell research & therapy · 2023Article
- Fetal allotransplant recipients are resistant to graft-versus-host disease.Experimental hematology · 2023Article
- Regenerative medicine: prenatal approaches.The Lancet. Child & adolescent health · 2022Review
- Experimental and clinical progress of in utero hematopoietic cell transplantation therapy for congenital disorders.Frontiers in pharmacology · 2022Review
- Maternal microchimerism and cell-mediated immune-modulation enhance engraftment following semi-allogenic intrauterine transplantation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Gene and Stem Cell Therapies for Fetal Care: A Review.JAMA pediatrics · 2020Review
- Regulatory T cells promote alloengraftment in a model of late-gestation in utero hematopoietic cell transplantation.Blood advances · 2020Article
- Prenatal stem cell therapy for inherited diseases: Past, present, and future treatment strategies.Stem cells translational medicine · 2020Review
- Review
- Mechanistic Insights into Factor VIII Immune Tolerance Induction via Prenatal Cell Therapy in Hemophilia A.Current stem cell reports · 2019Article
- In Utero Transplantation of Expanded Autologous Amniotic Fluid Stem Cells Results in Long-Term Hematopoietic Engraftment.Stem cells (Dayton, Ohio) · 2019Article
- Therapeutic expression of human clotting factors IX and X following adeno-associated viral vector-mediated intrauterine gene transfer in early-gestation fetal macaques.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Depletion of murine fetal hematopoietic stem cells with c-Kit receptor and CD47 blockade improves neonatal engraftment.Blood advances · 2018Article
- Pre-Existing Maternal Antibodies Cause Rapid Prenatal Rejection of Allotransplants in the Mouse Model of In Utero Hematopoietic Cell Transplantation.Journal of immunology (Baltimore, Md. : 1950) · 2018Article
- Maternal and Fetal Immune Response to in Utero Stem Cell Transplantation.Current stem cell reports · 2018Article
- A comparison of intrauterine hemopoietic cell transplantation and lentiviral gene transfer for the correction of severe β-thalassemia in a HbbTh3/+ murine model.Experimental hematology · 2018Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
The lack of fetal immune responses to foreign antigens, i.e., fetal immunologic tolerance, is the most compelling rationale for prenatal stem cell and gene therapy. However, the frequency of engraftment following in utero hematopoietic cell transplantation (IUHCT) in the murine model is reduced in allogeneic, compared with congenic, recipients. This observation supports the existence of an immune barrier to fetal transplantation and challenges the classic assumptions of fetal tolerance. Here, we present evidence that supports the presence of an adaptive immune response in murine recipients of IUHCT that failed to maintain engraftment. However, when IUHCT recipients were fostered by surrogate mothers, they all maintained long-term chimerism. Furthermore, we have demonstrated that the cells responsible for rejection of the graft were recipient in origin. Our observations suggest a mechanism by which IUHCT-dependent sensitization of the maternal immune system and the subsequent transmission of maternal alloantibodies to pups through breast milk induces a postnatal adaptive immune response in the recipient, which, in turn, results in the ablation of engraftment after IUHCT. Finally, we showed that non-fostered pups that maintained their chimerism had higher levels of Tregs as well as a more suppressive Treg phenotype than their non-chimeric, non-fostered siblings. This study resolves the apparent contradiction of induction of an adaptive immune response in the pre-immune fetus and confirms the potential of actively acquired tolerance to facilitate prenatal therapeutic applications.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.