RESUMEN
OBJECTIVE: In utero hematopoietic stem cell transplantation (IUHSCT) is a promising therapy for a variety of congenital disorders. Our objective was to determine the optimal time in gestation for IUHSCT in a canine model. METHODS: IUHSCT was performed in day 31-50 (term 63) fetal canines with CD34+ cells isolated from paternal bone marrow at doses of 0.09-3.4 × 109 CD34+ cells/kg and T cells (CD3+/CD5+) from paternal blood at 0.11-1.1 × 109 cells/kg. Engraftment was assayed using PCR-based chimerism analysis (SRY gene detection for female recipients, and unique microsatellite loci for both sexes). RESULTS: Microchimerism and chimerism were present in multiple recipients across most gestational ages at transplant. Maximal engraftment was obtained in hematopoietic tissues in transplants performed at 42 days. At extremes of recipient gestational age, minimal to no engraftment was seen. CONCLUSION: Fetal age at the time of IUHSCT plays an important role in achieving engraftment in our canine model.
Asunto(s)
Desarrollo Fetal , Supervivencia de Injerto , Enfermedad Injerto contra Huésped/prevención & control , Trasplante de Células Madre Hematopoyéticas/métodos , Animales , Antígenos CD34/metabolismo , Trasplante de Médula Ósea/efectos adversos , Trasplante de Médula Ósea/inmunología , Quimera , Perros , Femenino , Genes sry , Edad Gestacional , Enfermedad Injerto contra Huésped/embriología , Enfermedad Injerto contra Huésped/inmunología , Enfermedad Injerto contra Huésped/metabolismo , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Masculino , Repeticiones de Microsatélite , Trasplante de Células Madre de Sangre Periférica/efectos adversos , Embarazo , Linfocitos T/inmunología , Linfocitos T/metabolismo , Linfocitos T/trasplanteRESUMEN
During pregnancy maternal and fetal cells commute back and forth leading to fetal microchimerism in the mother and maternal microchimerism in the child that can persist for years after the birth. Chimeric fetal and maternal cells can be hematopoietic or can differentiate into somatic cells in multiple organs, potentially acting as targets for 'autoimmunity' and so have been implicated in the pathogenesis of autoimmune diseases that resemble graft-versus-host disease after stem cell transplantation. Fetal cells have been found in women with systemic lupus erythematosus, both in the blood and a target organ, the kidney, suggesting that they may be involved in pathogenesis. Future studies will address how the host immune system normally tolerates maternal and fetal cells or how the balance may change during autoimmunity.
