METHODS FOR GENERATING FUNCTIONAL HEMATOPOIETIC STEM CELLS

Abstract: described in the present application are methods for preparing populations of hematopoietic stem cells (hscs), e.g., autologous and/or allogenic hscs, using mechanical stretching or trpv4 agonists, and methods of use of the hscs in transplantation. in some embodiments, the methods include providing a population comprising hemogenic endothelial (he) cells, and (i) contacting the he cells with an amount of an agonist of transient receptor potential cation channel-subfamily vanilloid member 4 (trpv4); and/or (ii) subjecting the cells to cyclic 2-dimensional stretching, for a time and under conditions sufficient to stimulating endothelial-to-hsc transition. also provided herein are methods for treating subjects who have, bone marrow, metabolic, and immune diseases; the methods include administering to the subject a therapeutically effective amount of hematopoietic stem cells (hscs) obtained by a method described herein.

Inventor(s): Dhvanit I. Shah, George Q. Daley

CPC Classification: C12N5/0647 ({Haematopoietic stem cells; Uncommitted or multipotent progenitors})

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