Placental drug delivery for treatment of congenital hematopoietic disorders

Journal of Pediatric Surgery
S Christopher DerderianTippi C MacKenzie

Abstract

The success of in utero hematopoietic cell transplantation (IUHCTx) hinges on successful conditioning strategies of the host to overcome barriers to engraftment. The "space" barrier is a reflection of a finite number of hematopoietic stem cell (HSC) niches within the host. Independent of the number of donor HSCs transplanted, engraftment is frequently low. By conditioning fetal mice using a monoclonal antibody against the c-kit receptor (ACK2) found on HSCs, we can effectively increase space for donor HSC engraftment. We questioned whether simple placental injection of ACK2 early in gestation could effectively deplete host HSCs within the fetal liver and neonatal bone marrow. In this set of experiments, we injected mice with ACK2 (5μg/fetus) or PBS at E11.5-12.5 and harvested the fetal liver at 2 and 4days and the neonatal bone marrow at 7days following injection. Survival and total number of HSCs within the fetal liver or bone marrow were quantified and compared. Survival between the treated and control group was similar (73% and 71%, respectively). The total number of HSCs within the fetal liver was not significantly lower following ACK2 treatment compared to PBS injected fetuses at 2days but was by 4days. Additionally, ACK2 ...Continue Reading

References

Dec 12, 1996·The New England Journal of Medicine·A W FlakeE D Zanjani
Mar 17, 2004·PLoS Biology·Julie L ChristensenIrving L Weissman
Mar 9, 2006·American Journal of Obstetrics and Gynecology·Kirstin GolombeckMichael R Harrison
Sep 4, 2007·Obstetrics and Gynecology·Faris Mujezinovic, Zarko Alfirevic
Nov 24, 2007·Science·Agnieszka CzechowiczDeepta Bhattacharya
Dec 17, 2008·Developmental Biology·Alicia BárcenaSusan J Fisher
Jan 20, 2011·The Journal of Clinical Investigation·Amar NijagalTippi C MacKenzie

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Citations

Jul 20, 2021·Advanced Drug Delivery Reviews·José das NevesBruno Sarmento

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