Fetal hematogenous routing of a donor hematopoietic stem cell line in a healthy syngeneic model of transamniotic stem cell therapy

Abstract

Background/PurposeIn utero administration of hematopoietic stem cells (HSCs) has a variety of actual or potential clinical applications but is hindered by invasive, morbid administration techniques. We sought to determine whether donor HSCs could reach the fetal circulation after simple intra-amniotic delivery in a syngeneic rat model of transamniotic stem cell therapy (TRASCET). MethodsPregnant Lewis rat dams underwent volume-matched intra-amniotic injections in all fetuses (n = 90) on gestational day 17 (E17; term=E21-22) of a suspension of commercially available syngeneic Lewis rat HSCs labeled with luciferase (n = 37 fetuses) or an acellular suspension of recombinant luciferase (n = 53). HSC phenotype was confirmed by flow cytometry. Fetuses were euthanized at term for screening of luciferase activity at select anatomical sites. Statistical comparisons were by Fisher's exact test. ResultsAmong survivors (47/90; 52.2%), donor HSCs were identified selectively in the placenta (p = 0.003), umbilical cord (p < 0.001), bone marrow (p < 0.001), thymus (p = 0.009), bowel (p = 0.003), kidney (p = 0.022), and skin (p < 0.001) when compared with acellular luciferase controls. ConclusionsDonor hematopoietic stem cells undergo hematogenous routing and can reach the fetal bone marrow after simple intra-amniotic delivery in a syngeneic rat model. Transamniotic stem cell therapy may become a practicable, minimally invasive strategy for the prenatal administration of these cells.