Fetal Hematogenous Routing of a Donor Hematopoietic Stem Cell Line in a Healthy Syngeneic Model of Transamniotic Stem Cell Therapy
Stefanie P Lazow, MD; Ina Kycia, PhD; Daniel F Labuz, MD; David Zurakowski, PhD; Dario O Fauza, MD, PhD
Boston Children's Hospital, Boston, MA
Background: In 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).
Methods: Pregnant 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). HSCs were at least 80% positive for CD34, CD117, SSEA3, SSEA4, Sox2, Oct4, and alkaline phosphatase. Fetuses were euthanized at term for screening of luciferase activity at select anatomical sites (Table). Positive luminescence was defined as relative light unit values exceeding the mean plus 2 standard deviations of blanks. Statistical comparisons were by Fisher’s exact test.
Results: Among survivors (47/90; 52.2%), donor HSCs were identified selectively in the placenta, umbilical cord, bone marrow, and thymus (p=0.003, p<0.001, p<0.001, and p=0.009, respectively) when compared with acellular luciferase controls (Table). Conclusions: Donor hematopoietic stem cells can reach the fetal circulation, including 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.
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