Compositions and methods for induced tissue regeneration in mammalian species
Aspects of the present invention include methods and compositions related to the modulation of molecules regulating the regenerative potential of cells and tissues in the embryonic state and the loss thereof in later fetal and adult stages of development. Said methods and compositions have uses in research in stem cell biology and in increasing regenerative potential in fetal and adult tissues otherwise incapable of regeneration.
1. A method of enhancing wound healing in a subject comprising administering to a wound an siRNA that targets a COX7A1 mRNA to inhibit expression from the COX7A1 mRNA at or near the site of the wound.
2. The method of claim 1 , wherein the subject is a mammal.
3. The method of claim 2 , wherein the mammal is a human.
4. The method of claim 1 , wherein the site of the wound is connective tissue.
5. The method of claim 1 , wherein the site of the wound is skin.
6. The method of claim 5 , wherein the wound is a trauma wound, a surgical wound, or a wound associated with a disease.
7. The method of claim 5 , wherein the wound is a burn, a scrape injury or other skin loss.
8. The method of claim 5 , wherein the wound is associated with grafted skin.
9. The method of claim 5 , wherein the wound involves a hair follicle or an epithelial cell.
10. The method of claim 1 , further comprising administering a cell to the wound, separately or in the same composition as the siRNA.
11. The method of claim 10 , wherein the cell is an adult stem cell, an induced pluripotent stem cell, a progenitor cell or a differentiated cell.
12. The method of claim 11 , wherein the progenitor cell is a mesenchymal progenitor cell, a neural progenitor cell, an endothelial progenitor cell, a hair follicle progenitor cell, a neural crest progenitor cell, a mammary progenitor cell, a lung progenitor cell, a muscle progenitor cell, an adipose-derived progenitor cell, an epithelial progenitor cell, a hematopoietic progenitor cell, or a combination thereof.
13. The method of claim 11 , wherein the differentiated cell is a chondrocyte, an osteoblast, a keratinocyte, a hepatocyte, a myoblast, or a combination thereof.
14. The method of claim 1 , wherein the siRNA is administered with one or more compounds that form a hydrogel in situ.
15. The method of claim 1 , further comprising administering to the wound one or more siRNAs, each of which targets a COMT, TRIM4, CAT, PSMD, SHMT, LOC205251, ZNF280D, S100A6, MGMT, DYNLT3, NAALADL1, TSPYL5, IAH1, C18orf56, RPS7, FDPS, ELOVL6, INSIG1, ACAT2, or MAOA mRNA to inhibit expression of the mRNA at or near the site of the wound.
16. The method of claim 15 , wherein the subject is a mammal.
17. The method of claim 16 , wherein the mammal is a human.
18. The method of claim 15 , wherein the site of the wound is connective tissue.
19. The method of claim 15 , wherein the site of the wound is skin.
20. A kit for enhancing wound healing according to the method of claim 1 , the kit comprising: (a) an siRNA that targets a COX7A1 mRNA to inhibit expression from the COX7A1 mRNA; and (b) one or more siRNAs, each of which targets a COMT, TRIM4, CAT, PSMD, SHMT, LOC205251, ZNF280D, S100A6, MGMT, DYNLT3, NAALADL1, TSPYL5, IAH1, C18orf56, RPS7, FDPS, ELOVL6, INSIG1, ACAT2, or MAOA mRNA to inhibit expression from the mRNA.
21. The kit of claim 20 , further comprising a cell.
22. The kit of claim 21 , wherein the cell is an adult stem cell, an induced pluripotent stem cell, a progenitor cell or a differentiated cell.
23. The kit of claim 22 , wherein the progenitor cell is a mesenchymal progenitor cell, a neural progenitor cell, an endothelial progenitor cell, a hair follicle progenitor cell, a neural crest progenitor cell, a mammary progenitor cell, a lung progenitor cell, a muscle progenitor cell, an adipose-derived progenitor cell, an epithelial progenitor cell, a hematopoietic progenitor cell, or a combination thereof.
24. The kit of claim 22 , wherein the differentiated cell is a chondrocyte, an osteoblast, a keratinocyte, a hepatocyte, a myoblast, or a combination thereof.
25. The kit of claim 20 , further comprising one or more compounds that form a hydrogel in situ.
26. The kit of claim 25 , wherein the one or more compounds comprises a monomer, polymer, initiating agent, cross-linking agent or any combination thereof.