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.