Method for treating or preventing a pancreatic dysfunction
The present invention provides a method for improving pancreatic function in a subject in need thereof, the method comprising administering to the subject STRO-1 + cells and/or progeny cells thereof and/or soluble factors derived therefrom. The method of the invention is useful for treating and/or preventing and/or delaying the onset or progression of a disorder resulting from or associated with pancreatic dysfunction, e.g., resulting from abnormal endocrine or exocrine function of the pancreas.
1. A method for improving pancreatic function in a subject in need thereof, wherein the subject suffers from a pancreatic dysfunction associated with the endocrine and/or exocrine function of the pancreas, the method comprising administering to the subject STRO-1 + cells and/or progeny cells thereof and/or soluble factors derived therefrom.
2. The method of claim 1 wherein the administration of STRO-1 + cells and/or progeny cells thereof and/or soluble factors derived therefrom promotes regeneration of pancreatic beta cells and/or pancreatic islets.
3. The method of claim 1 wherein the administration of STRO-1 + cells and/or progeny cells thereof and/or soluble factors derived therefrom reduces blood glucose levels and/or increases blood/serum insulin levels in the subject.
4. The method of claim 1 wherein the administration of STRO-1 + cells and/or progeny cells thereof and/or soluble factors derived therefrom increases the number of pancreatic beta cells and/or increases the number of pancreatic beta cells relative to pancreatic alpha cells and/or reduces the number of pancreatic alpha cells and/or increases the number of pancreatic islets in the subject.
5. The method of claim 1 wherein the administration of STRO-1 + cells and/or progeny cells thereof and/or soluble factors derived therefrom increases pancreatic and duodenal homeobox factor-1 (PDX-1) expression and/or increases the number of PDX-1 expressing cells in a pancreas of the subject.
6. The method of claim 1 wherein the administration of STRO-1 + cells and/or progeny cells thereof and/or soluble factors derived therefrom induces or promotes arteriogenesis or angiogenesis in the pancreas of the subject.
7. The method according to claim 1 , wherein the pancreatic dysfunction is associated with or causes aberrant levels of insulin, glucagon, somatostatin, pancreatic polypeptide, trypsinogen, chymotrypsinogen, elastase, carboxypeptidase, pancreatic lipase or amylase.
8. The method according to claim 7 , wherein the aberrant level of glucagon is caused by a glucagon secreting tumor.
9. The method according to claim 1 wherein the pancreatic dysfunction:
(i) is associated with or causes malabsorption of nutrients;
(ii) is associated with pancreatitis, pancreatic insufficiency, acquired autoimmune deficiency syndrome, cancer, cystic fibrosis or Zollinger Ellison syndrome;
(iii) results in hypoglycemia or hyperglycemia, reduced serum amino acid levels, proteinuria, or necrolytic migratory erythema; and/or
(iv) is associated with or causes a carbohydrate metabolism disorder.
10. The method according to claim 9 , wherein the carbohydrate metabolism disorder is caused by reduced insulin production by the pancreas or by reduced amylase production by the pancreas.
11. The method according to claim 9 wherein the carbohydrate metabolism disorder is selected from the group consisting of idiopathic Type 1 diabetes, early-onset Type II diabetes, youth-onset atypical diabetes, maturity onset diabetes of the young, malnutrition-related diabetes, gestational diabetes, conditions of impaired glucose tolerance, conditions of impaired fasting plasma glucose, metabolic acidosis, ketosis, hyperglycemia, hypoinsulinemia, insulin resistance, alpha mannosidosis, beta mannosidosis, fructose intolerance, fucosidosis, galactosemia, Leigh disease, mucolipidosis and mucopolysaccharidoses.
12. The method according to claim 1 , wherein the STRO-1 + cells and/or progeny cells thereof and/or soluble factors derived therefrom are administered directly into the bloodstream of a subject.
13. The method according to claim 12 , wherein the STRO-1 + cells and/or progeny cells thereof and/or soluble factors derived therefrom are administered intra-arterially.
14. The method according to claim 1 , wherein the STRO-1 + cells administered to the subject are STRO-1 bri , and/or express tissue non-specific alkaline phosphatase (TNAP) and/or the progeny cells and/or soluble factors are derived from STRO-1 + cells that are STRO-1 bri and/or express TNAP.
15. The method according to claim 1 for treating or delaying the progression of pancreatic dysfunction, wherein the STRO-1 + cells and/or progeny cells thereof and/or soluble factors derived therefrom are administered following diagnosis of the disorder.
16. The method according to claim 1 additionally comprising monitoring or detecting onset and/or progression of pancreatic dysfunction and/or blood glucose levels and/or blood/serum insulin levels and/or the number of beta cells and/or the number of alpha cells and/or the number of pancreatic islets and/or the number of PDX-1 expressing cells and/or the amount of PDX-1 expression and/or the number of blood vessels.
17. The method according to claim 1 , wherein the STRO-1 + cells and/or progeny cells thereof and/or soluble factors derived therefrom are administered in the form of a composition comprising said STRO-1 + cells and/or progeny cells thereof and/or soluble factors derived therefrom and a carrier and/or excipient.
18. The method according to claim 17 , wherein the composition additionally comprises a factor that induces or enhances differentiation of progenitor cells into vascular cells or the composition comprises a tissue specific committed cell.