Enhanced differentiation of mesenchymal stem cells

Abstract

Isolated populations of mesenchymal stem cells (MSCs) are provided, including mammalian mesenchymal stem cells (MSCs) characterized by the lack of CD54 (CD54 − ) or low cell-surface CD54 (CD54 low ). Methods of in vitro cell differentiation and methods of treatment using said isolated populations are also provided.

1 . A method of cell transplantation into a human recipient, the method comprising:
 (1) isolating a population of mammalian mesenchymal stem cells (MSCs), wherein the isolated population of MSCs has a cell-surface expression profile comprising CD54 (CD54 low ) or no cell-surface expression of CD54 (CD54 − ), CD73 + , CD90 + , CD105 + , CD11a − , CD19 − , CD34 − , and CD45 − ; and   (2) administering said isolated population of MSCs of step (1) to a human recipient, wherein the isolated population of MSCs of step (1) are allogeneic with respect to the human recipient, and wherein said administering results in immunosuppression in said human recipient.   
     
     
         2 . The method of  claim 1 , wherein the isolated population of MSCs isolated in step (1) comprises greater than 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% of CD54 low  or CD54 −  MSCs. 
     
     
         3 . The method of  claim 1 , wherein the isolated population of MSCs in step (1) comprises less than 5%, 4%, 3%, 2%, 1%, 0.5%, or 0.1% of contaminating fibroblasts. 
     
     
         4 . The method of  claim 1 , wherein the isolated population of MSCs in step (1) is adipose-derived MSCs or bone-marrow derived MSCs. 
     
     
         5 . The method of  claim 1 , wherein the isolated population of MSCs in step (1) expresses cell-surface CD73 at a level at least 1.25-fold, 1.5-fold, 1.75-fold, or 2-fold greater than allogeneic CD54 +  MSCs or MSCs that are unsorted or unseparated on the basis of cell-surface CD54 expression. 
     
     
         6 . The method of  claim 1 , wherein the administering in step (2) is done by injecting the isolated population into a human recipient. 
     
     
         7 . The method of  claim 1 , wherein the isolated population of MSCs in step (1) has enhanced MSC differentiation potential in comparison to CD54 +  MSCs or MSCs that are unsorted or unseparated on the basis of cell-surface CD54 expression. 
     
     
         8 . The method of  claim 1 , wherein the isolated population of MSCs in step (1) are rodent, bovine, equine, primate, or human MSCs. 
     
     
         9 . The method of  claim 1 , wherein the isolated population of MSCs in step (1) further express at least one cell-surface marker chosen from the group consisting of HLA-G, HLA-E, indoleamine-pyrrole 2,3, dioxygenase (INDO), and CD200. 
     
     
         10 . An isolated population of MSCs having a cell-surface expression profile comprising CD54 low  or CD54 − , CD73 + , CD90 + , CD105 + , CD11a − , CD19 − , CD34 − , and CD45 − . 
     
     
         11 . The isolated population of MSCs of  claim 10 , wherein the isolated population of MSCs is adipose-derived MSCs or bone-marrow derived MSCs. 
     
     
         12 . The isolated population of MSCs of  claim 10  comprising greater than 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% of CD54low or CD54− MSCs. 
     
     
         13 . The isolated population of MSCs of  claim 10 , wherein the isolated composition comprises less than 5%, 4%, 3%, 2%, 1%, 0.5%, or 0.1% of contaminating fibroblasts. 
     
     
         14 . A pharmaceutical composition comprising the isolated population of MSCs of  claim 10  and a pharmaceutically acceptable carrier. 
     
     
         15 . The isolated population of MSCs of  claim 10  having enhanced MSC differentiation potential in comparison to CD54 +  MSCs or MSCs that are unsorted or unseparated on the basis of cell-surface CD54 expression. 
     
     
         16 . The isolated population of MSCs of  claim 10 , wherein the isolated population of MSCs expresses cell-surface CD73 at a level at least 1.25-fold, 1.5-fold, 1.75-fold, or 2-fold greater than allogeneic CD54 +  MSCs or MSCs that are unsorted or unseparated on the basis of cell-surface CD54 expression. 
     
     
         17 . The isolated population of MSCs of  claim 10 , wherein the MSCs are rodent, bovine, equine, primate, or human MSCs. 
     
     
         18 . The isolated population of MSCs of  claim 10 , wherein the isolated population of MSCs further expresses at least one cell-surface marker chosen from the group consisting of HLA-G, HLA-E, indoleamine-pyrrole 2,3, dioxygenase (INDO), and CD200.