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Blood, Vol. 95 No. 11 (June 1), 2000:
pp. 3620-3627
Cotransplantation of human stromal cell progenitors into preimmune
fetal sheep results in early appearance of human donor cells in
circulation and boosts cell levels in bone marrow at later time points
after transplantation
Graça Almeida-Porada,
Christopher D. Porada,
Nam Tran, and
Esmail D. Zanjani
Department of Veterans Affairs Medical Center, University of Nevada
Reno, Reno, NV.
Both in utero and postnatal hematopoietic stem cell (HSC)
transplantation would benefit from the development of approaches that
produce increased levels of engraftment or a reduction in the period of
time required for reconstitution. We used the in utero model of
human-sheep HSC transplantation to investigate ways of improving
engraftment and differentiation of donor cells after transplantation.
We hypothesized that providing a more suitable microenvironment in the
form of human stromal cell progenitors simultaneously with the
transplanted human HSC would result in higher rates of engraftment or
differentiation of the human cells in this xenogeneic model. The
results presented here demonstrate that the cotransplantation of both
autologous and allogeneic human bone marrow-derived stromal cell
progenitors resulted in an enhancement of long-term engraftment of
human cells in the bone marrow of the chimeric animals and in earlier
and higher levels of donor cells in circulation both during gestation
and after birth. By using marked stromal cells, we have also
demonstrated that injected stromal cells alone engraft and remain
functional within the sheep hematopoietic microenvironment. Application
of this method to clinical HSC transplantation could potentially lead
to increased levels of long-term engraftment, a reduction in the time
for hematopoietic reconstitution, and a means of delivery of foreign
genes to the hematopoietic system.
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