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Biological properties of mesenchymal stem cells in the multiple myeloma tumor microenvironment

donderdag, 13 september, 2012 - 17:00
Campus: Brussels Health Campus
Faculteit: Medicine and Pharmacy
auditorium 1
Song Xu
doctoraatsverdediging

Multiple Myeloma (MM) is a hematological malignancy characterized by a
clonal proliferation of plasma cells in the bone marrow (BM). The crosstalk
between BM stromal cells and MM cells supports the proliferation, survival,
migration and drug resistance of MM cells, as well as osteoclastogenesis
and angiogenesis. Mesenchymal stem cells (MSCs) are multipotent
progenitors that can differentiate into a variety of cell types and are the
main precursor cells of the BM stroma. However, the direct involvement of
MSCs in the pathophysiology of MM has not been well addressed.

With this research work we determined that MSCs can be attracted by MM
cell produced CCL25 and favor MM cell growth in vitro and in vivo.
Moreover, we demonstrated that dysregulated Notch signaling and miR-
135b expression are two possible mechanisms involved in the impaired
osteogenic differentiation of MSCs from MM patients. In addition, we
developed an optimal protocol to culture murine MSCs in vitro, and
discovered that HDAC inhibitor Vorinostat does not induce bone loss in
contrast to previous findings.

Collectively, our data suggest that MSC-based cytotherapy has a potential
risk for MM disease progression or relapse. Targeting endogeneous MSCs
osteogenesis by inhibiting Notch signaling or miR-135b expression might
be a promising strategy to control bone disease in MM patients.

Bijlage: 
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