Stem Cell Factor-Like Protein Scfa1 and Uses Thereof
Methods for stimulating epithelial cell proliferation and for treating oral and gastrointestinal disorders are described. The methods use compositions comprising stem cell factor-like protein A1 (SCFA1) polypeptides and polynucleotides.
1 . A method of stimulating epithelial cell proliferation in a subject in need thereof, said method comprising administering to said subject a therapeutically effective amount of a composition comprising a stem cell factor-like protein A1 (SCFA1) polypeptide and a pharmaceutically acceptable carrier.
2 . The method of claim 1 , wherein the SCFA1 polypeptide comprises the contiguous sequence of amino acids of SEQ ID NO:2, 4, 6, 8, or 10, or a sequence of amino acids with at least 90% sequence identity to the contiguous sequence of amino acids of SEQ ID NO:2, 4, 6, 8 or 10.
3 . The method of claim 3 , wherein the SCFA1 polypeptide comprises the contiguous sequence of amino acids of SEQ ID NO:2, 4, 6, 8, or 10.
4 . The method of claim 1 , wherein the method comprises stimulating epithelial cell proliferation in the oral or gastrointestinal tract.
5 . The method of claim 4 , wherein the method comprises stimulating epithelial cell proliferation in the esophagus.
6 . The method of claim 4 , wherein the method comprises stimulating epithelial cell proliferation in the small intestine.
7 . The method of claim 4 , wherein the method comprises stimulating epithelial cell proliferation in the large intestine.
8 . The method of claim 4 , wherein the method comprises stimulating epithelial cell proliferation in the stomach.
9 . The method of claim 4 , wherein the method comprises stimulating epithelial cell proliferation in the oral cavity.
10 . A method of treating a gastrointestinal disorder or oral mucosal disorder in a mammalian subject in need thereof, said method comprising administering to said subject a therapeutically effective amount of a composition comprising a stem cell factor-like protein A1 (SCFA1) polypeptide and a pharmaceutically acceptable carrier.
11 . The method of claim 10 , wherein the SCFA1 polypeptide comprises the contiguous sequence of amino acids of SEQ ID NO:2, 4, 6, 8, or 10, or a sequence of amino acids with at least 90% sequence identity to the contiguous sequence of amino acids of SEQ ID NO:2, 4, 6, 8 or 10.
12 . The method of claim 11 , wherein the SCFA1 polypeptide comprises the contiguous sequence of amino acids of SEQ ID NO:2, 4, 6, 8, or 10.
13 . The method of claim 10 , wherein the disorder is mucositis, inflammatory bowel disease, or short bowel syndrome.
14 . A method for treating a mammalian subject at risk for damage to the epithelial cells lining at least a portion of the oral or gastrointestinal tract, the method comprising administering to said subject a therapeutically effective amount of a composition comprising a stem cell factor-like protein A1 (SCFA1) polypeptide and a pharmaceutically acceptable carrier.
15 . The method of claim 14 , wherein the SCFA1 polypeptide comprises the contiguous sequence of amino acids of SEQ ID NO:2, 4, 6, 8, or 10, or a sequence of amino acids with at least 90% sequence identity to the contiguous sequence of amino acids of SEQ ID NO:2, 4, 6, 8 or 10.
16 . The method of claim 15 , wherein the SCFA1 polypeptide comprises the contiguous sequence of amino acids of SEQ ID NO:2, 4, 6, 8, or 10.
17 . The method of claim 14 wherein the subject has undergone or will undergo radiation therapy.
18 . The method of claim 14 wherein the subject has undergone or will undergo chemotherapy.
19 . An adenoviral vector comprising a polynucleotide encoding a stem cell factor-like protein A1 (SCFA1) polypeptide operably associated with an expression control sequence.
20 . The adenoviral vector of claim 19 , wherein the SCFA1 polypeptide comprises the contiguous sequence of amino acids of SEQ ID NO:2, 4, 6, 8, or 10, or a sequence of amino acids with at least 90% sequence identity to the contiguous sequence of amino acids of SEQ ID NO:2, 4, 6, 8 or 10.
21 . The adenoviral vector of claim 20 , wherein the SCFA1 polypeptide comprises the contiguous sequence of amino acids of SEQ ID NO:2, 4, 6, 8, or 10.
22 . A pharmaceutical composition comprising the adenoviral vector of claim 19 and a pharmaceutically acceptable carrier.
23 . A method of stimulating epithelial cell proliferation in a subject in need thereof, said method comprising administering to said subject a therapeutically effective amount of the pharmaceutical composition of claim 22 .
24 . A method of stimulating epithelial cell proliferation in a subject in need thereof, said method comprising administering to said subject a therapeutically effective amount of a pharmaceutical composition comprising a vector encoding a stem cell factor-like protein A1 (SCFA1) polypeptide operably associated with an expression control sequence and a pharmaceutically acceptable carrier.
25 - 29 . (canceled)
30 . A method of modulating the wnt/β-catenin signaling pathway in a subject in need thereof, said method comprising administering to said subject an amount of a composition comprising a stem cell factor-like protein A1 (SCFA1) polypeptide and a pharmaceutically acceptable carrier effective to activate the pathway.
31 . The method of claim 30 , wherein the SCFA1 polypeptide comprises the contiguous sequence of amino acids of SEQ ID NO:2, 4, 6, 8, or 10, or a sequence of amino acids with at least 90% sequence identity to the contiguous sequence of amino acids of SEQ ID NO:2, 4, 6, 8 or 10.
32 . The method of claim 31 , wherein the SCFA1 polypeptide comprises the contiguous sequence of amino acids of SEQ ID NO:2, 4, 6, 8, or 10.