Mesenchymal stem cell differentiation
The present invention provides for methods and compositions for treating or preventing arthritis and joint injury.
1. A method of ameliorating or treating arthritis or joint injury in a mammal, the method comprising administering to a joint of the mammal a composition comprising an effective amount of a C-terminal fibrinogen like domain (FLD) ANGPTL3 polypeptide consisting of:
i. an amino acid sequence at least 95% identical to any one of SEQ ID NO: 5, SEQ ID NO: 6, or SEQ ID NO: 7, or
ii. an amino acid sequence at least 95% identical to any one of SEQ ID NO: 5, SEQ ID NO: 6, or SEQ ID NO: 7 fused to a human serum albumin (HSA), an immunoglobulin heavy chain constant region (Fc), a polyhistidine, a glutathione S transferase (GST), a thioredoxin, a protein A, a protein G, or a maltose binding protein (MBP);
thereby ameliorating or treating arthritis or joint injury in the mammal.
2. The method of claim 1 , wherein the polypeptide is PEGylated.
3. The method of claim 1 , wherein the individual has arthritis or joint injury.
4. The method of claim 1 , wherein the arthritis is selected from the group consisting of osteoarthritis, trauma arthritis, and autoimmune arthritis.
5. The method of claim 1 , wherein the mammal is a human, a dog, or a cat.
6. The method of claim 1 , wherein the composition further comprises hyaluronic acid.
7. The method of claim 1 , wherein the amino acid sequence comprises SEQ ID NO: 5, 6 or 7.
8. The method of claim 1 , wherein the amino acid sequence is SEQ ID NO: 5, SEQ ID NO: 6, or SEQ ID NO: 7.
9. A method of inducing differentiation of mesenchymal stem cells into chondrocytes, the method comprising contacting mesenchymal stem cells with a sufficient amount of a C-terminal fibrinogen like domain (FLD) ANGPTL3 polypeptide consisting of:
i. an amino acid sequence at least 95% identical to any one of SEQ ID NO: 5, SEQ ID NO: 6, or SEQ ID NO: 7, or
ii. an amino acid sequence at least 95% identical to any one of SEQ ID NO: 5, SEQ ID NO: 6, or SEQ ID NO: 7 fused to a human serum albumin (HSA), an immunoglobulin heavy chain constant region (Fc), a polyhistidine, a glutathione S transferase (GST), a thioredoxin, a protein A, a protein G, or a maltose binding protein (MBP);
to induce differentiation of the stem cells into chondrocytes.
10. The method of claim 9 , wherein the polypeptide is PEGylated.
11. The method of claim 9 , wherein the method is performed in vitro.
12. The method of claim 9 , wherein the method is performed in vivo and the stem cells are present in a mammal.
13. The method of claim 12 , wherein the mammal is a human, a dog, or a cat.
14. The method of claim 12 , wherein the mammal has arthritis or joint injury.
15. The method of claim 14 , wherein the arthritis is selected from the group consisting of osteoarthritis, trauma arthritis, and autoimmune arthritis.
16. The method of claim 9 wherein the amino acid sequence comprises SEQ ID NO: 5, SEQ ID NO: 6 or SEQ ID NO: 7.
17. The method of claim 9 , wherein the amino acid sequence is SEQ ID NO: 5, SEQ ID NO: 6, or SEQ ID NO: 7.