Project #2

Human ossicles for iPS-HSC development and Leukemia modeling

The emergence of induced pluripotent stem cells (iPS) has offered unprecedented opportunities in developmental biology and regenerative medicine. Generated from patient cells, iPS maintains their genetic features, allowing deciphering healthy or pathological processes in a personalized fashion. Applied to hematopoiesis, this technology holds enormous promises towards generating transplantable hematopoietic stem cells (HSCs), or modeling hematological malignancies. If iPS-derived hematopoietic cells can be obtained in vitro, yet fully functional iPS-HSCs could not be produced. Similarly, iPS blood cells generated from B cell leukemic patients fail at recapitulating the associated disease-specific patterns. This calls for the exploration of new tools capable of improving the formation and maturation of iPS blood populations. 

Inspired from the fetal hematopoietic development in bones, we here propose the exploitation of the human ossicle (hOss) technology. These hOss consist in miniaturized bone organs composed of a human mesenchymal niche shown to support hematopoiesis. We hypothesize that the hOss can support the engraftment and maturation of healthy iPS-HSCs, but also provide a platform for modeling B-cell malignancy using iPS derived blood cells. If successful, this project bears high relevance for the modeling of human healthy and malignant hematopoiesis and will prompt the development of innovative regenerative therapies.