Research Report 2010 - MDC

Figure 22a2b2a: Dual liposomes significantly reduced the number of metastases ofhuman MT-3 breast cancer in nude mice by preventing the formationof fibrin clots with proliferating tumor cells in a lung capillary(Micrograph: blue: tumor cells, red: fibrin).2b: Mitoxantrone (MTO) loaded liposomes significantly (*) inhibitedthe intracerebral growth of MT-3 tumor (blue area in micrographs)after intravenous treatment, indicating a better transcellular transportacross the blood-brain barrier.Liposomes were also developed to inhibit metastasis inthe brain. Endothelial and epithelial barriers play animportant role in the drug exchange between bloodand tissues. Such tight cellular linings especially limitthe drug transport across the blood brain barrier.Liposomes were designed to be used as drug transportersinto the brain. They were characterized concerningtheir membrane properties, their uptake by andtheir transcytotic transport across an epithelial barrierin vitro and were tested concerning their therapeuticeffect on breast cancer metastasis in the brain. Electronparamagnetic resonance measurements revealed aclear correlation between membrane fluidity of theliposomal bilayer and transcytosis. Liposomes with thehelper lipids DOPE and Perifosine showed the highesttranscytosis across a tight monolayer resulting in a fivefoldincreased transport of a marker into the basalmedium of a transwell system in comparison to controlliposomes. Liposomes containing both the helper lipidsand Mitoxantrone as cytotoxic drug were shown tosignificantly inhibit tumor growth in the brain of nudemice by 61 % (Figure 2 b). It is expected that transcellulartransport across the blood brain barrier can furtherbe enhanced by fluid liposomes conjugated with a peptidefor an active targeting to a specific receptor at theblood brain barrier. This project is currently ongoing.Stem cell differentiation and transplantation intomouse modelsExperimental and clinical studies showed that thetransplantation of different stem cell types can contributeto the regeneration of injured tissues. The aimof our work was the evaluation and comparison of thespontaneous and directed hepatic differentiation ofadult CD34 + cord blood stem cells and human embryonicstem cells.Human embryonic SA002 stem cells showed spontaneousin vitro differentiation into mesodermal, endodermaland ectodermal cell types. Hepatocyte conditionedmedium and co-culture systems with murinehepatocytes were investigated regarding their potentialto induce stem cell differentiation. Gene expressionpattern of cultivated CD34 + cells in hepatocyte conditionedmedium resulted in an only moderate regulationof genes associated with cell cycle and cytoskeletonorganization. In contrast to the restricted transdifferentiationpotential of CD34 + cells, SA002 cells in co-culture138 Cancer Research