autologous blood and marrow transplantation - Blog Science ...

Henschler et al. 557
an increase of repopulation potential after 4 days in cytokine-supported culture.
The importance of flt-3 ligand for the maintenance of repopulating cells has been
demonstrated previously by Dao et al. 26
They showed that flt-3 ligand was needed
to maintain the repopulation potential for a period longer than 24 hours, up to 72
hours. In agreement with these observations, Larochelle et al. 27
found that the
transplantation potential of CD34 +
CD38" cord blood cells was lost when they
were incubated in the presence of other cytokine combinations.
The main components with an influence on the survival of breast cancer cells
during ex vivo expansion were found to be serum-free medium and the use of
recombinant immunotoxins. To a limited degree, TGF-B1 was also able to decrease
numbers of tumor cells. Whereas some previous studies have shown an influence
of hematopoietic cytokines such as IL-l and -6 on tumor cell growth ex vivo using
established breast cancer cell lines, 28,29
our results with primary breast cancer cells
are in line with the findings of Emerman et al. 30
who, also using primary cells,
found no effect of cytokines on tumor cell growth. The results with this serum-free
medium preparation show that stem/progenitor cells do not have a major impact on
tumor cell survival. The result from the short term (3-day) experiments using PKHlabeled
tumor cells in the presence or absence of CD34 +
cells showed that in
serum-free medium, an efficient tumor cell depletion is observed very early during
the culture time.
Taking together our results, we propose that a relatively short incubation of
CD34 +
blood progenitor cells is required for the maintenance of bone
marrow-repopulating stem cells, offering the possibility to efficiently eliminate
tumor cells from autologous transplants. This possibility is underscored by kinetic
analyses of tumor cell elimination by immunotoxins, which also showed that these
molecules may act within hours, up to a 3- to 4-day short time period. 9
Given the
(already) low incidences of solid tumor cells within autologous transplants in
patients with breast carcinoma, a combination of the purging mechanisms that may
be achieved during ex vivo expansion could, in addition to immunoselection of
transplants, lead to practically tumor-free transplants for clinical application.
ACKNOWLEDGMENTS
We would like to thank Elisete de Lima-Hahn and Jutta Aumann for excellent
technical assistance.
REFERENCES
1. To LB, Haylock DN, Simmons PJ, Juttner CA: The biology and clinical uses of blood
stem cells. Stood 89:2233-2258, 1997.
2. Berenson RJ, Andrews RG, Bensinger WI, Kalamasz D, Knitter G, Buckner CD, Bernstein