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In utero depletion of fetal hematopoietic stem cells improves engraftment after neonatal transplantation in mice.
- Source :
-
Blood [Blood] 2014 Aug 07; Vol. 124 (6), pp. 973-80. Date of Electronic Publication: 2014 May 30. - Publication Year :
- 2014
-
Abstract
- Although in utero hematopoietic cell transplantation is a promising strategy to treat congenital hematopoietic disorders, levels of engraftment have not been therapeutic for diseases in which donor cells have no survival advantage. We used an antibody against the murine c-Kit receptor (ACK2) to deplete fetal host hematopoietic stem cells (HSCs) and increase space within the hematopoietic niche for donor cell engraftment. Fetal mice were injected with ACK2 on embryonic days 13.5 to 14.5 and surviving pups were transplanted with congenic hematopoietic cells on day of life 1. Low-dose ACK2 treatment effectively depleted HSCs within the bone marrow with minimal toxicity and the antibody was cleared from the serum before the neonatal transplantation. Chimerism levels were significantly higher in treated pups than in controls; both myeloid and lymphoid cell chimerism increased because of higher engraftment of HSCs in the bone marrow. To test the strategy of repeated HSC depletion and transplantation, some mice were treated with ACK2 postnatally, but the increase in engraftment was lower than that seen with prenatal treatment. We demonstrate a successful fetal conditioning strategy associated with minimal toxicity. Such strategies could be used to achieve clinically relevant levels of engraftment to treat congenital stem cell disorders.<br /> (© 2014 by The American Society of Hematology.)
- Subjects :
- Animals
Animals, Newborn
Female
Fetal Stem Cells immunology
Hematopoietic Stem Cells immunology
Mice
Mice, Inbred C57BL
Pregnancy
Proto-Oncogene Proteins c-kit administration & dosage
Proto-Oncogene Proteins c-kit antagonists & inhibitors
Proto-Oncogene Proteins c-kit immunology
Stem Cell Niche immunology
Fetal Stem Cells cytology
Fetal Therapies methods
Hematopoietic Stem Cell Transplantation methods
Hematopoietic Stem Cells cytology
Transplantation Conditioning methods
Subjects
Details
- Language :
- English
- ISSN :
- 1528-0020
- Volume :
- 124
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Blood
- Publication Type :
- Academic Journal
- Accession number :
- 24879814
- Full Text :
- https://doi.org/10.1182/blood-2014-02-550327