Bioengineering of human ossicles as advanced in vivo hematopoietic model

ongoing

hOssicle aims at developing miniaturized human bone organs in mice to be used as advanced model of healthy and malignant human hematopoiesis. In Europe, 80 million people are estimated to suffer from blood disorders. When at all existing, treatments are poorly effective: 92 % of new drugs successful in preclinical testing (animals and in vitro culture systems) fail in clinical trials. This urgently calls for the development of superior models, to refine our understanding of human hematopoiesis and better predict patient´ therapy efficacy. My laboratory has developed unique human mesenchymal lines capable of forming “human ossicles” by recapitulation of endochondral ossification -the developmental process of bone formation. These ossicles form subcutaneously in mice and display a similar structure and function to native mouse bones, but rely on human mesenchymal cells reconstituting a complex bone marrow environment specifically supporting the development of human hematopoiesis. hOssicle will offer the unprecedented custom engineering of human bones to understand the functional organization of its hematopoietic compartment. By genetic reprogramming of mesenchymal lines, I aim at controlling the molecular and cellular composition of the ossicles and study the corresponding impact on hematopoietic development. Finally, I envision the engineering of patient-specific ossicles with mesenchymal and leukemic blood cells from the same individual towards recapitulation of the disease setting. This will be a significant breakthrough, by offering the study of malignancy progression and drug-testing in a personalized in vivo context for cancer remission. By combining principles of bone development & tissue engineering, hOssicle proposes an “organ engineering” approach applied to hematopoiesis. The implications run from the identification of key factors controlling the production of blood cell types to the personalized modelling of leukemia and test of therapies.