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Placental drug delivery for treatment of congenital hematopoietic disorders.
- Source :
-
Journal of pediatric surgery [J Pediatr Surg] 2015 Sep; Vol. 50 (9), pp. 1517-20. Date of Electronic Publication: 2014 Dec 31. - Publication Year :
- 2015
-
Abstract
- Objective: 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.<br />Methods: In this set of experiments, we injected mice with ACK2 (5 μg/fetus) or PBS at E11.5-12.5 and harvested the fetal liver at 2 and 4 days and the neonatal bone marrow at 7 days following injection. Survival and total number of HSCs within the fetal liver or bone marrow were quantified and compared.<br />Results: 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 2 days but was by 4 days. Additionally, ACK2 resulted in a significant reduction in the number of HSCs within neonatal mice 7 days after treatment.<br />Conclusion: Survival following placental ACK2 injection is comparable to control animals and provides a simple non-invasive strategy to deliver ACK2 into the fetal circulation which successfully depletes the host HSCs.<br /> (Copyright © 2015 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Antibodies, Monoclonal pharmacology
Antibodies, Monoclonal therapeutic use
Bone Marrow drug effects
Female
Fetus cytology
Hematopoietic Stem Cells drug effects
Injections
Liver cytology
Mice
Mice, Inbred C57BL
Pregnancy
Proto-Oncogene Proteins c-kit immunology
Antibodies, Monoclonal administration & dosage
Fetal Therapies methods
Hematopoietic Stem Cell Transplantation methods
Placenta
Transplantation Conditioning methods
Subjects
Details
- Language :
- English
- ISSN :
- 1531-5037
- Volume :
- 50
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Journal of pediatric surgery
- Publication Type :
- Academic Journal
- Accession number :
- 25783323
- Full Text :
- https://doi.org/10.1016/j.jpedsurg.2014.12.021