Pd-l1 expressing hematopoietic stem cells and uses

Abstract

Embodiments disclosed here provide engineered modified hematopoietic stem cells (HSCs), artificially prostaglandin E2 (PGE2)-stimulated HSCs, compositions comprising these HSCs, methods of using these modified HSCs for treating autoimmune diseases and disorders and for suppressing the immune system. In particular, the engineered modified HSCs or PGE2-stimulated HSCs express the surface marker, programmed cell death-1 ligand 1 (PD-L1).

What is claimed: 
     
         1 . A population of modified hematopoietic stem cells (HSCs) where the cells carry an exogenous copy of a nucleic acid encoding a programmed cell death-1 receptor ligand (PD-L1). 
     
     
         2 . The population of modified HSCs of  claim 1 , wherein the cells are expressing PD-L1. 
     
     
         3 . The population of modified HSCs of  claim 1 , wherein the nucleic acid is a copy DNA (cDNA), or a genomic DNA, or is integrated into the genome of the cells. 
     
     
         4 .- 10 . (canceled) 
     
     
         11 . The population of modified HSCs of  claim 1 , wherein prior to the modification, the HSCs are obtained from the bone marrow, umbilical cord, amniotic fluid, chorionic villi, cord blood, placental blood or peripheral blood. 
     
     
         12 . (canceled) 
     
     
         13 . The population of modified HSCs of  claim 1 , wherein the HSCs are derived from a healthy individual or from an individual with a diagnosed disease or disorder. 
     
     
         14 . (canceled) 
     
     
         15 . The population of modified HSCs of  claim 13 , wherein the diagnosed disease or disorder is an autoimmune disease or disorder. 
     
     
         16 . The population of modified HSCs of  claim 15 , wherein the autoimmune disease or disorder is Type 1 diabetes (TID). 
     
     
         17 .- 19 . (canceled) 
     
     
         20 . The population of modified HSCs of  claim 1 , wherein the HSC cells are produced by a method comprising:
 a) contacting a sample of HSCs with a vector carrying an exogenous copy of a nucleic acid encoding a PD-L1 to modify the HSCs;   b) ex vivo culturing the resultant modified cells from the contacting; and   c) establishing the expression of PD-L1 on the modified HSCs, thereby producing a population of modified HSCs cells expressing PD-L1.   
     
     
         21 . The population of modified HSCs of  claim 20 , wherein the method further comprises establishing that there is at least one-fold increase in the number of PD-L1+ expressing cells compared to non-modified cells. 
     
     
         22 . An ex vivo method of producing a population of modified, PD-L1+ expressing hematopoietic stem cells (HSCs), the method comprising:
 a) contacting a sample of HSCs with a vector carrying an exogenous copy of a nucleic acid encoding a PD-L1 to modify the HSCs whereby the exogenous copy of a nucleic acid is introduced into the HSCs;   b) ex vivo culturing the resultant modified cells from the contacting; and   c) establishing the expression of PD-L1 on the modified HSCs, thereby producing a population of modified HSCs cells expressing PD-L1.   
     
     
         23 . The ex vivo method of  claim 22 , wherein the method further comprises establishing that there is at least one-fold increase in the number of PD-L1+ expressing cells compared to non-modified cells. 
     
     
         24 .- 34 . (canceled) 
     
     
         35 . A composition comprising the hematopoietic stem cells of  claim 1 . 
     
     
         36 . A composition comprising the hematopoietic stem cells produced by the method of  claim 22 . 
     
     
         37 . A method of treating an autoimmune disorder in a subject in need thereof, the method comprising administering to a subject a composition comprising the hematopoietic stem cells in  claim 35 . 
     
     
         38 . The method of  claim 37 , wherein the autoimmune disorder is Type 1 diabetes (TID). 
     
     
         39 . The method of  claim 37 , wherein the HSCs are autologous to the recipient subject, or are non-autologous and allogenic non-autologous and xenogeneic to the recipient subject, are non-autologous and xenogeneic to the recipient subject. 
     
     
         40 .- 42 . (canceled) 
     
     
         43 . A method of modulating an immune response in a subject comprising:
 a. providing a population of hematopoietic stem cells (HSCs);   b. contacting sample of HSCs with a vector carrying an exogenous copy of a nucleic acid encoding a PD-L1;   c. ex vivo culturing the resultant modified cells from the contacting;   d. establishing the expression of PD-L1 on the modified HSCs, thereby producing a population of modified HSCs cells expressing PD-L1; and   e. transplanting said population of PD-L1+ expressing HSCs into a recipient subject, thereby modulating the immune response in the recipient subject.   
     
     
         44 . (canceled) 
     
     
         45 . (canceled) 
     
     
         46 . The method of  claim 43 , wherein the population of HSCs is autologous or is allogeneic or is xenogeneic to the recipient subject. 
     
     
         47 .- 50 . (canceled) 
     
     
         51 . The method of  claim 43 , the method further comprising selecting a recipient subject in need of immune response modulation. 
     
     
         52 .- 55 . (canceled)