An in vivo competitive repopulation assay for various sources of human hematopoietic stem cells

Citation
Es. Rosler et al., An in vivo competitive repopulation assay for various sources of human hematopoietic stem cells, BLOOD, 96(10), 2000, pp. 3414-3421
Citations number
52
Categorie Soggetti
Hematology,"Cardiovascular & Hematology Research
Journal title
BLOOD
ISSN journal
00064971 → ACNP
Volume
96
Issue
10
Year of publication
2000
Pages
3414 - 3421
Database
ISI
SICI code
0006-4971(20001115)96:10<3414:AIVCRA>2.0.ZU;2-Y
Abstract
The marrow repopulating potential (MRP) of different sources of human hemat opoietic stem cells (HSCs) was directly compared using an in vivo assay in which severe combined immunodeficient disease (SCID) mice were implanted wi th human fetal bones. HSCs from 2 human lymphocyte antigen (HLA)-mismatched donors were injected individually or simultaneously into the fetal bones o f a 3rd distinct HLA type and donor and recipient myeloid and lymphoid cell s were identified after 8 to 10 weeks. The study compared the MRP of umbili cal cord blood (CB) and adult bone marrow (ABM) CD34(+) cells as well as gr afts of each type expanded ex vivo. Equal numbers of CB and ABM CD34(+) cel ls injected individually demonstrated similar abilities to establish multil ineage hematopoiesis. However, when CB and ABM cells were transplanted simu ltaneously, the engraftment of CB cells was markedly superior to ABM. CB an d ABM CD34(+) cells were expanded ex vivo using either a porcine microvascu lar endothelial cell (PMVEC)based coculture system or a stroma-free expansi on system. Primary CB CD34(+) cells or CD34(+) cells expanded in either cul ture system demonstrated a similar ability to engraft. However, the MRP of expanded grafts simultaneously injected with primary CB cells was uniformly inferior to primary CB cells. CD34(+) cell grafts expanded in the stroma-f ree system, furthermore, outcompeted CD34(+) cells expanded using the PMVEC coculture system. The triple HLA-mismatched SCID-hu model represents a nov el in vivo stem cell assay system that permits the direct demonstration of the functional consequences of ex vivo HSC expansion and ontogeny-related d ifferences in HSCs. (C) 2000 by The American Society of Hematology.