In vitro 2-dimensional co-culture systems of LT-HSCs and osteoblastic niche cells and methods of establishing them are provided. For example, in certain aspects methods of screening people suffering from a disorder caused by dysfunction of osteoblastic niche cells, using said co-culture systems are described. In further aspects, methods for screening a candidate substance for treatment of a disorder caused by dysfunction of osteoblastic niche cells are provided. The present invention also concerns methods and therapeutic compositions of treating a patient suffering from a disorder caused by dysfunction of osteoblastic niche cells.