A silk-based bone marrow model to predict individual response to old and new drugs for increasing platelet count in inherited thrombocytopenias

Inherited thrombocytopenias are rare disorders characterized by reduced production of platelets from the bone marrow due to genetic defects. Patients therefore present a reduced number of platelets in blood resulting in hemorrhages that can occur spontaneously or after small traumas or even minor surgery. Therapeutic options for patients with inherited thrombocytopenias are currently very scarce. In fact, only one drug has been tested in a limited number of patients and only some of them have obtained significant improvements. Difficulties in identifying effective treatments derive also from the fact that the mechanisms of reduced platelet production are still poorly known and different among different patients. This project aims to develop a device, called “bioreactor”, that closely reproduces the whole process of platelet production from the progenitor cells (stem cells) that can be obtained from a small amount of venous blood. The bioreactor exploits an innovative technology based on a silk “scaffold” manipulated in order to reproduce in our laboratories a sort of artificial bone marrow. This device will be used to systematically study the defective platelet production of several patients affected by different forms of inherited thrombocytopenia starting from a small sample of their blood. Moreover, the bioreactor will be applied to study the efficacy of molecules that can be potentially used as drugs to overcome the defects of platelet production. Thus, the project aims to develop an innovative tool for investigation of the mechanisms underlying different forms of inherited thrombocytopenia and identification of novel potential drugs. Moreover, the device will allow us to understand which molecules are most effective in each single patient, thus paving the road to a personalized treatment of inherited thrombocytopenias.