PURPOSE OF REVIEW: Prenatal stem cell and gene therapy approaches are amongst the few therapies that can promise the birth of a healthy infant with specific known genetic diseases. This review describes fetal immune cell signaling and its potential influence on donor cell engraftment, and summarizes mechanisms of central T cell tolerance to peripherally-acquired antigen in the context of prenatal therapies for Hemophilia A. RECENT FINDINGS: During early gestation, different subsets of antigen presenting cells take up peripherally-acquired, non-inherited antigens and induce the deletion of antigen-reactive T-cell precursors in the thymus, demonstrating the potential for using prenatal cell and gene therapies to induce central tolerance to FVIII in the context of prenatal diagnosis/therapy of Hemophilia A. SUMMARY: Prenatal cell and gene therapies are promising approaches to treat several genetic disorders including Hemophilia A and B. Understanding the mechanisms of how FVIII-specific tolerance is achieved during ontogeny could help develop novel therapies for HA and better approaches to overcome FVIII inhibitors.
PURPOSE OF REVIEW: Prenatal stem cell and gene therapy approaches are amongst the few therapies that can promise the birth of a healthy infant with specific known genetic diseases. This review describes fetal immune cell signaling and its potential influence on donor cell engraftment, and summarizes mechanisms of central T cell tolerance to peripherally-acquired antigen in the context of prenatal therapies for Hemophilia A. RECENT FINDINGS: During early gestation, different subsets of antigen presenting cells take up peripherally-acquired, non-inherited antigens and induce the deletion of antigen-reactive T-cell precursors in the thymus, demonstrating the potential for using prenatal cell and gene therapies to induce central tolerance to FVIII in the context of prenatal diagnosis/therapy of Hemophilia A. SUMMARY: Prenatal cell and gene therapies are promising approaches to treat several genetic disorders including Hemophilia A and B. Understanding the mechanisms of how FVIII-specific tolerance is achieved during ontogeny could help develop novel therapies for HA and better approaches to overcome FVIII inhibitors.
Authors: J D Massaro; C E V Wiezel; Y C N Muniz; E M Rego; L C O de Oliveira; C T Mendes-Junior; A L Simões Journal: Haemophilia Date: 2011-06-07 Impact factor: 4.287
Authors: D M W Balak; S C Gouw; I Plug; E P Mauser-Bunschoten; A H J T Vriends; J E M Van Diemen-Homan; F R Rosendaal; J G van der Bom Journal: Haemophilia Date: 2012-01-18 Impact factor: 4.287
Authors: Chadwick Wu; Masa Endo; Byung H Yang; Melissa A Radecki; Patrick F Davis; Philip W Zoltick; Ryan M Spivak; Alan W Flake; Richard E Kirschner; Hyun-Duck Nah Journal: Mol Ther Date: 2012-10-23 Impact factor: 11.454