Enhanced differentiation of mesenchymal stem cells
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 for enhancing MSC differentiation potential comprising:
(1) isolating a population of MSCs on the basis of CD54 cell-surface expression, wherein the population of MSCs is isolated from MSCs that are adipose-derived MSCs or bone-marrow derived MSCs, and, wherein the isolated population of MSCs has a cell-surface expression profile comprising CD54 low or CD54 − , CD73 + , CD90 + , CD105 + , CD11a − , CD19 − , CD34 − , and CD45 − , and wherein the population of MSCs is isolated by a method comprising the use of anti-CD54 antibodies; and
(2) differentiating said isolated population of MSCs such that the percentage of cells differentiated is greater than CD54+ MSCs or a population of MSCs that are unsorted or unseparated on the basis of CD54 cell-surface expression, wherein the differentiation occurs in vitro, and wherein the differentiation is adipogenic or osteogenic.
2. The method of claim 1 , wherein the population of MSCs isolated in step (1) comprise greater than 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% of MSCs with a cell-surface expression profile comprising CD54 low or CD54 − .
3. The method of claim 2 , wherein the population of MSCs isolated in step (1) comprise less than 5%, 4%, 3%, 2%, 1%, 0.5%, or 0.1% of contaminating fibroblasts.
4. The method of claim 3 , wherein the population of MSCs isolated in step (1) is substantially free of fibroblasts.
5. The method of claim 1 , wherein the population of MSCs isolated in step (1) further express cell-surface HLA-G and/or HLA-E.
6. The method of claim 1 , wherein the population of MSCs isolated in step (1) further express cell-surface indoleamine-pyrrole 2,3, dioxygenase (INDO).
7. The method of claim 1 , wherein the population of MSCs isolated in step (1) further express cell surface CD200.
8. The method of claim 1 , wherein the population of MSCs isolated in step (1) express cell-surface CD73 at a level at least 1.3-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.
9. The method of claim 1 , wherein in step (2) the percentage of cells differentiated is about 1.5-fold, 2-fold, 3-fold, 4-fold, or 5-fold greater than CD54 + MSCs or a population of MSCs that are unsorted or unseparated on the basis of CD54 cell-surface expression.
10. The method of claim 1 , wherein the MSCs are rodent, bovine, equine, or primate MSCs.
11. The method of claim 1 , wherein the MSCs are human MSCs.