Methods of enhancing stem cell engraftment
OwnerDavid Williams, Gabriel Ghiaurinventors
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Abstract
The present invention provides improved methods and pharmaceutical compositions for enhancing stem cell engraftment, comprising the administration of an effective amount of a modulator of RhoGTPases.
Claims60
A method for enhancing bone marrow engraftment in an subject in need thereof comprising administering to the subject (i) a bone marrow graft and (ii) a Rho modulator, wherein the Rho modulator is administered in an amount effective to promote engraftment of the bone marrow in the subject.
A method for autologous hematopoietic cell transplantation in a subject receiving cytoreductive therapy, comprising:
- (a) removing hematopoietic stem or progenitor cells from the subject prior to cytoreductive therapy;
- (b) expanding the hematopoietic stem or progenitor cells ex vivo with a cell expanding amount of a Rho modulator to provide a cellular preparation comprising an expanded population of hematopoietic stem or progenitor cells;
- (c) administering the cellular preparation to the subject following cytoreductive therapy;
- and (d) administering a Rho modulator, wherein the Rho modulator is administered in an amount and dosage regime effective to promote engraftment of the cells in the subject.
A method of testing for an agent that modulates the binding between a guanine nucleotide exchange factor and a RhoGTPase comprising:
- contacting a polypeptide comprising a GTPase, or a biologically-active fragment thereof, with an agent suspected of modulating the activity of the RhoGTPase;
- and detecting the activity of the GTPase.
Dependencies are inferred from the claim text.