Hematopoietic Stem Cell Interactions 
with Their Microenvironment 
The survival and proliferation of hematopoietic 
stem cells in vivo and in vitro is dependent on di- 
rect interaction of these cells with cells or extracel- 
lular matrix proteins comprising the hematopoietic 
microenvironment in the bone marrow cavity. 
Various cell types in this complex environment can 
be immortalized, using recombinant retroviral vec- 
tors containing the simian virus 40 large T (SV40 
LT) oncogene. This procedure has allowed the de- 
tailed analysis of interactions between the stem cells 
and their microenvironment. 
Previous work in Dr. Williams's laboratory had 
demonstrated that primitive hematopoietic cells 
that can give rise to all blood lineages adhere to 
specific proteins within the bone marrow cavity. Dr. 
Moritz has continued investigations into the role 
that adhesion of primitive cells to this protein plays 
in blood cell development. He has used gene 
transfer via retroviral vectors to study the effect 
of adhesion on primitive hematopoietic cell 
proliferation. 
In another series of experiments, Dr. Xunxiang 
Du has performed detailed investigations on the ef- 
fects of administering a growth factor, interleukin- 
11 (lL-1 1), produced by cells in the bone marrow 
cavity, on blood cell formation in the mouse after 
radiation- or chemotherapy-induced marrow injury. 
Radiation and chemotherapy are often used to treat 
cancer, and bone marrow injury is a serious side ef- 
fect of these therapies. 
Dr. Du has demonstrated that treatment of mice 
with IL-11 can accelerate the recovery of bone 
marrow from these toxic side effects and signifi- 
cantly reduce mortality in mice treated with very 
high doses of radiation and chemotherapy. These 
beneficial side effects may prove useful in cancer 
therapies. In addition. Dr. Du has demonstrated that 
IL-1 1 regulates the amount of lipid accumulation in 
the bone marrow cavity. 
Dr. Pamela Kooh is taking a similar approach to 
study the normal function of the growth factor IL- 1 1 
in the bone marrow. Using a series of experiments 
done both in vitro and in vivo. Dr. Kooh hopes to 
demonstrate the role of IL- 11 in normal bone 
marrow as well as in fetal blood development. 
Dr. Manas Majumdar is investigating the biology 
of another protein produced by bone marrow cells. 
The protein. Steel factor, is deficient in certain mice 
with a genetic form of bone marrow disease. Dr. 
Majumdar is investigating the importance of the way 
Steel factor is presented to developing blood cells in 
the marrow cavity. The presentation of Steel factor is 
evidently important for human blood cell develop- 
ment in tissue culture systems, as previously shown 
by Dr. Denis Toksoz in Dr. Williams's laboratory. By 
studying the mouse. Dr. Majumdar can better ex- 
plore the role of Steel factor protein in vivo. 
Dr. Williams is also Associate Professor and 
Kipp Investigator of Pediatrics and Associate Pro- 
fessor of Medical and Molecular Genetics at In- 
diana University School of Medicine, Herman B 
Wells Center for Pediatrics Research, and Asso- 
ciate Professor of Pediatrics at the fames Whit- 
comb Riley Hospital for Children, Indianapolis. 
Articles 
Hollander, G.A., Luskey, B.D., Williams, D.A., and 
Burakoff, S.J. 1992. Functional expression of 
human CDS in fully reconstituted mice after 
retroviral-mediated gene transfer of hematopoi- 
etic stem cells, f Immunol 149:438-444. 
Luskey, B.D., Rosenblatt, M., Zsebo, K., and Wil- 
liams, D.A. 1992. Stem cell factor, interleukin-3, 
and interleukin-6 promote retroviral-mediated 
gene transfer into murine hematopoietic stem 
cells. 5/00^/80:396-402. 
Majumdar, M.K., and Williams, D.A. 1992. A 
rapid method of minipreparations of plasmid 
DNA. Biotechniques 13:18. 
Matsui, Y., Toksoz, D., Nishikawa, S., Nishikawa, 
S.-l., Williams, D.A., Zsebo, K., and Hogan, 
B.L.M. 1991. Effect of 5ree/ factor and leukaemia 
inhibitory factor on murine primordial germ cells 
in culture. Nature 353:750-752. 
Paul, S R., Perez-Atayde, A., and Williams, D.A. 
1992. Interstitial pulmonary disease associated 
with dyskeratosis congenita [letter]. Am f Pediatr 
Hematol Oncol 14:89-92. 
Skalnik, D.G., Dorfman, D.M., Williams, D.A., and 
Orkin, S.H. 1991- Restriction of neuroblastoma 
to the prostate gland in transgenic mice. Mol Cell 
Biol 11:4518-4527. 
Toksoz, D., Zsebo, K.M., Smith, K.A., Hu, S., Bran- 
kow, D., Suggs, S.V., Martin, F.H., and Williams, 
D.A. 1992. Support of human hematopoiesis in 
long-term bone marrow cultures by murine stro- 
mal cells selectively expressing the membrane- 
bound and secreted forms of the human homolog 
of the steel gene product, stem cell factor. Proc 
Natl Acad Sci USA 89:7350-7354. 
288 
