THE USE OF RET AGONIST MOLECULES FOR HAEMATOPOIETIC STEM CELL EXPANSION PROTOCOLS AND TRANSPLANTATION THERAPY AND A RET AGONIST KIT

摘要

The present disclosure relates to the use of RET, a transmembrane tyrosine kinase receptor, agonist molecules for Haematopoietic Stem Cell (HSC) expansion protocols and HSC transplantation therapy. RET signaling molecules are expressed by HSCs and Ret ablation leads to reduced HSC numbers. RET signals provide HSCs with critical Bcl2 and Bcl2l1 surviving cues, downstream of p38/MAP kinase and CREB activation. Accordingly, enforced expression of RET down-stream targets, Bcl2 or Bcl2l1, is sufficient to restore the activity of Ret null progenitors in vivo. Remarkably, activation of RET improves HSC survival or maintenance and in vivo transplantation efficiency, thus opening new horizons to the usage of RET agonist in HSC expansion and transplantation protocols. Additionally, the present disclosure describes a kit comprising RET agonist molecules, to be used in HSC expansion protocols and transplantation therapy.