TY - JOUR
T1 - Soluble factor(s) produced by adult bone marrow stroma inhibit in vitro proliferation and differentiation of fetal liver BFU-E by inducing apoptosis
AU - Roy, Vivek
AU - Verfaillie, Catherine M.
PY - 1997/8/15
Y1 - 1997/8/15
N2 - Hematopoiesis occurs in different organs during fetal development. Several studies suggest that the growth of hematopoietic progenitors at one stage of ontogenic maturation may not be supported by a microenvironment from a different ontogenic stage. To determine if human fetal liver (FL) clonogenic progenitors can develop in an adult bone marrow (ABM) microenvironment, we compared growth of BFU-E and CFU-GM from 7-14-wk-old FL, 11-20-wk-old fetal bone marrow (FBM), umbilical cord blood (UCB), or ABM in clonogenic medium with or without ABM stroma. In contrast to BFU-E from FBM, UCB, or ABM, soluble factor(s) produced by ABM stroma severely suppressed growth of 98% of FL BFU-E by inducing apoptosis of cells beyond early erythroblast stage. The nature of the soluble factor remains unknown, although we have evidence that it is heat labile with molecular mass < 10 kD. Antibody neutralization studies indicate that TGF-β1, IL-1, TNF-α, macrophage inflammatory protein (MIP)-Iα, or IFN-γ are not responsible. The observation that FL progenitors may not be capable of differentiating when transferred to an ABM microenvironment may have important implications for FL transplantation into postnatal recipients. Further, this demonstrates that ontogenic stage-specific interactions between hematopoietic progenitors and their microenvironment are important for the normal development of hematopoiesis.
AB - Hematopoiesis occurs in different organs during fetal development. Several studies suggest that the growth of hematopoietic progenitors at one stage of ontogenic maturation may not be supported by a microenvironment from a different ontogenic stage. To determine if human fetal liver (FL) clonogenic progenitors can develop in an adult bone marrow (ABM) microenvironment, we compared growth of BFU-E and CFU-GM from 7-14-wk-old FL, 11-20-wk-old fetal bone marrow (FBM), umbilical cord blood (UCB), or ABM in clonogenic medium with or without ABM stroma. In contrast to BFU-E from FBM, UCB, or ABM, soluble factor(s) produced by ABM stroma severely suppressed growth of 98% of FL BFU-E by inducing apoptosis of cells beyond early erythroblast stage. The nature of the soluble factor remains unknown, although we have evidence that it is heat labile with molecular mass < 10 kD. Antibody neutralization studies indicate that TGF-β1, IL-1, TNF-α, macrophage inflammatory protein (MIP)-Iα, or IFN-γ are not responsible. The observation that FL progenitors may not be capable of differentiating when transferred to an ABM microenvironment may have important implications for FL transplantation into postnatal recipients. Further, this demonstrates that ontogenic stage-specific interactions between hematopoietic progenitors and their microenvironment are important for the normal development of hematopoiesis.
KW - Apoptosis
KW - BFU-E
KW - Bone marrow stroma
KW - Cell differentiation
KW - Hematopoiesis
UR - http://www.scopus.com/inward/record.url?scp=0030817083&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0030817083&partnerID=8YFLogxK
U2 - 10.1172/JCI119607
DO - 10.1172/JCI119607
M3 - Article
C2 - 9259591
AN - SCOPUS:0030817083
SN - 0021-9738
VL - 100
SP - 912
EP - 920
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
IS - 4
ER -