Format

Send to

Choose Destination
Dev Cell. 2014 Jun 9;29(5):621-628. doi: 10.1016/j.devcel.2014.04.013.

Effect of developmental stage of HSC and recipient on transplant outcomes.

Author information

1
Stem Cell Transplantation Program, Howard Hughes Medical Institute, Division of Pediatric Hematology/Oncology, Children's Hospital Boston and Dana Farber Cancer Institute, Boston, MA 02115, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA; Harvard Stem Cell Institute, Harvard University, Boston, MA 02115, USA.
2
Department of Pediatric Surgery, The University of Texas Medical School at Houston, Houston, TX 77030, USA.
3
Division of Experimental Hematology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
4
Department of Pediatrics, Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
5
Stem Cell Transplantation Program, Howard Hughes Medical Institute, Division of Pediatric Hematology/Oncology, Children's Hospital Boston and Dana Farber Cancer Institute, Boston, MA 02115, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA; Harvard Stem Cell Institute, Harvard University, Boston, MA 02115, USA. Electronic address: george.daley@childrens.harvard.edu.

Abstract

The first hematopoietic stem cells (HSCs) that engraft irradiated adult mice arise in the aorta-gonad-mesonephros (AGM) on embryonic day 11.5 (E11.5). However, at this stage, there is a discrepancy between the apparent frequency of HSCs depicted with imaging and their rarity when measured with limiting dilution transplant. We have attempted to reconcile this difference using neonatal recipients, which are more permissive for embryonic HSC engraftment. We found that embryonic HSCs from E9.5 and E10.5 preferentially engrafted neonates, whereas developmentally mature, definitive HSCs from E14.5 fetal liver or adult bone marrow (BM) more robustly engrafted adults. Neonatal engraftment was enhanced after treating adult BM-derived HSCs with interferon. Adult BM-derived HSCs preferentially homed to the liver in neonatal mice yet showed balanced homing to the liver and spleen in adults. These findings emphasize the functional differences between nascent and mature definitive HSCs.

PMID:
24914562
PMCID:
PMC4172398
DOI:
10.1016/j.devcel.2014.04.013
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center