ABCB5 POSITIVE MESENCHYMAL STEM CELLS AS IMMUNOMODULATORS
The present invention is directed to purified preparations of dermal mesenchymal stem cells that are characterized by the cell surface expression of the ABCB5 P-glycoprotein. The cells may be used for any purpose that mesenchymal stem cells from other course are used. For instance they may be administered to treat an organ transplant recipient to improve allograft survival or as a treatment to patients with autoimmune diseases such as multiple sclerosis and rheumatoid arthritis.
1 . A method for inducing tissue generation, comprising promoting differentiation of an isolated preparation of ABCB5 positive dermal mesenchymal stem cells, wherein ABCB5 positive dermal cells comprise at least 95% of the isolated preparation of ABCB5 positive dermal mesenchymal stem cells.
2 . The method of claim 1 , wherein the isolated preparation of ABCB5 positive dermal mesenchymal stem cells are first grown in an undifferentiated state through mitotic expansion.
3 . The method of claim 1 , wherein the isolated preparation of ABCB5 positive dermal mesenchymal stem cells are harvested and activated to differentiate into bone, cartilage, ligament, tendon, stroma, muscle and adipose tissue.
4 . The method of claim 1 , wherein the isolated preparation of ABCB5 positive dermal mesenchymal stem cells are seeded onto a matrix or scaffold.
5 . The method of claim 4 , wherein the matrix is a polymeric mesh or sponge.
6 . The method of claim 4 , wherein the matrix is a polymeric hydrogel.
7 . The method of claim 1 , wherein the ABCB5 positive dermal mesenchymal stem cells are injected into a soft or hard tissue defect.
8 . The method of claim 7 , wherein the tissue defect is a trauma or burn.
9 . A matrix seeded with a population of dermal stem cells, wherein at least 95% of the population of dermal stem cells are ABCB5+ dermal mesenchymal stem cells.
10 . The matrix of claim 9 , wherein the matrix is shaped to fill a tissue defect.
11 . The matrix of claim 9 , wherein the matrix is a collagen matrix.
12 .- 20 . (canceled)
21 . A method, comprising administering to a subject having received a transplanted tissue an isolated preparation of ABCB5 positive immunomodulatory dermal mesenchymal stem cells in an effective amount to modulate immune molecule expression in cells of the subject, wherein ABCB5 positive dermal cells comprise at least 95% of the isolated preparation of ABCB5 positive immunomodulatory dermal mesenchymal stem cells.
22 . The method of claim 21 , wherein the subject has graft-versus-host disease.
23 . The method of claim 21 , wherein the isolated preparation of ABCB5 positive immunomodulatory dermal mesenchymal stem cells is administered to the subject in advance of the tissue.
24 . A method, comprising administering to a subject having an organ transplant an effective amount of ABCB5 positive dermal mesenchymal stem cells to promote allograft survival, wherein ABCB5 positive dermal cells comprise at least 95% of the isolated preparation of ABCB5 positive dermal mesenchymal stem cells.
25 . The method of claim 24 , wherein the allograft is selected from the group consisting of: heart; lungs; liver; and kidney.
26 . A method of treating autoimmune disease, comprising administering to a subject having autoimmune disease an effective amount of ABCB5 positive dermal mesenchymal stem cells to treat the autoimmune disease, wherein ABCB5 positive dermal cells comprise at least 95% of the isolated preparation of ABCB5 positive dermal mesenchymal stem cells.
27 . A method of treating liver disease, comprising administering to a subject having a liver disease an effective amount of ABCB5 positive dermal mesenchymal stem cells to treat the liver disease, wherein ABCB5 positive dermal cells comprise at least 95% of the isolated preparation of ABCB5 positive dermal mesenchymal stem cells.
28 . A method of treating a neurodegenerative disease, comprising administering to a subject having a neurodegenerative disease an effective amount of ABCB5 positive dermal mesenchymal stem cells to treat the neurodegenerative disease, wherein ABCB5 positive dermal cells comprise at least 95% of the isolated preparation of ABCB5 positive dermal mesenchymal stem cells and wherein the neurodegenerative disease is associated with an immune response against host cells.
29 . A method of treating cardiovascular disease, comprising administering to a subject having cardiovascular disease an effective amount of ABCB5 positive dermal mesenchymal stem cells to treat the cardiovascular disease, wherein ABCB5 positive dermal cells comprise at least 95% of the isolated preparation of ABCB5 positive dermal mesenchymal stem cells and, wherein the cardiovascular disease is associated with tissue remodeling.
30 . A method of treating kidney disease, comprising administering to a subject having a kidney disease an effective amount of ABCB5 positive dermal mesenchymal stem cells to treat the kidney disease, wherein ABCB5 positive dermal cells comprise at least 95% of the isolated preparation of ABCB5 positive dermal mesenchymal stem cells.