ArticleThrombosis and haemostasis2011
Factor VIII delivered by haematopoietic stem cell-derived B cells corrects the phenotype of haemophilia A mice.
Article in Thrombosis and haemostasis, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 22 citations in OpenAlex.
- In Vitro Conditioning of Adipose-Derived Mesenchymal Stem Cells by the Endothelial Microenvironment: Modeling Cell Responsiveness towards Non-Genetic Correction of Haemophilia A.International journal of molecular sciences · 2022Article
- Ex vivo editing of human hematopoietic stem cells for erythroid expression of therapeutic proteins.Nature communications · 2020Article
- Endothelial cells derived from patients' induced pluripotent stem cells for sustained factor VIII delivery and the treatment of hemophilia A.Stem cells translational medicine · 2020Article
- Mechanistic Insights into Factor VIII Immune Tolerance Induction via Prenatal Cell Therapy in Hemophilia A.Current stem cell reports · 2019Article
- Induction of Hematopoietic Microchimerism by Gene-Modified BMT Elicits Antigen-Specific B and T Cell Unresponsiveness toward Gene Therapy Products.Frontiers in immunology · 2016Article
- Stimulation of Liver X Receptor Has Potent Anti-HIV Effects in a Humanized Mouse Model of HIV Infection.The Journal of pharmacology and experimental therapeutics · 2015Article
- Extrahepatic sources of factor VIII potentially contribute to the coagulation cascade correcting the bleeding phenotype of mice with hemophilia A.Haematologica · 2015Article
- Gene therapy for hemophilia.Frontiers in bioscience (Landmark edition) · 2015Review
- Development of Gene Transfer for Induction of Antigen-specific Tolerance.Molecular therapy. Methods & clinical development · 2014Article
- Advanced therapies for the treatment of hemophilia: future perspectives.Orphanet journal of rare diseases · 2012Review
- Engineered Hematopoietic Stem Cells as Therapeutics for Hemophilia A.Journal of genetic syndromes & gene therapy · 2011Article
- Recent Advances in Gene Therapy for Hemophilia.Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/HemostasisReview
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The main impediments to clinical application of haematopoietic stem cell (HSC) gene therapy for treatment of haemophilia A are the bone marrow transplant-related risks and the potential for insertional mutagenesis caused by retroviral vectors. To circumvent these limitations, we have adapted a non-myeloablative conditioning regimen and directed factor VIII (FVIII) protein synthesis to B lineage cells using an insulated lentiviral vector containing an immunoglobulin heavy chain enhancer-promoter. Transplantation of lentiviral vector-modified HSCs resulted in therapeutic levels of FVIII in the circulation of all transplanted mice for the duration of the study (six months). Immunostaining of spleen cells showed that the majority of FVIII was synthesised by B220+ B cells and CD138+ plasma cells. Subsequent challenge with recombinant FVIII elicited at most a minor anti-FVIII antibody response, demonstrating induction of immune hyporesponsiveness. All transplant recipients exhibited clot formation and survived tail clipping, indicating correction of their haemophilic phenotype. Therapeutic levels of FVIII could be transferred to secondary recipients by bone marrow transplantation, confirming gene transfer into long-term repopulating HSCs. Moreover, short-term therapeutic FVIII levels could also be achieved in secondary recipients by adoptive transfer of HSC-derived splenic B cells. Our findings support pursuit of B cell-directed protein delivery as a potential clinical approach to treat haemophilia A and other disorders correctable by systemically distributed proteins.
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