Reliable and Predictive In Vitro Assays for Myelotoxicity and Cardiotoxicity of Kinase Inhibitors
Poster Apr 15, 2009
Kinase inhibitors (KIs) represent a new class of rationally designed drugs. The success of Imatinib has prompted the development of other KIs for the treatment of various cancers and inflammation. Although more successful than conventional therapies, myelotoxicity and cardiotoxicity are often major side effects of KIs. In order to predict if newly developed molecules demonstrated significant myelotoxicity or cardiotoxicity, we assessed a number of TKIs using in vitro models.
We found a distinct subpopulation of Tregs within BMSCs. Tregs and BMSCs in co-culture conferred neuroprotection that varied in a dose-dependent manner. Tregs minimized stem cell production of IL-6, a pro-inflammatory cytokine, and inhibited BMSC secretion of FGF-beta, a cytokine related to BMSC proliferation and differentiation. The ratio of Tregs found natively in BMSCs is optimally adapted to provide the maximum neuroprotective benefit of stem cell treatment after ischemic stroke.READ MORE