Bioadhesive directed somatic cell therapy
The subject invention is related to a cell-mediated gene therapy treatment using a cell composition that includes bioadhesive material. The bioadhesive material allows targeted and localized delivery of therapeutic somatic cells to the site of interest.
1. A composition comprising a treatment effective amount of a population of somatic fibroblast or chondrocyte cells transfected or transduced with a therapeutic gene, and an adhesive effective amount of buffy coat for administration into a joint space in a mammal in need thereof, wherein said cells and buffy coat material are autologous, syngeneic, or are allogeneic with respect to each other.
2. The composition according to claim 1 , wherein said gene encodes a cytokine.
3. The composition according to claim 2 , wherein said cytokine belongs to TGF-βsuperfamily.
4. The composition according to claim 3 , wherein said cytokine is TGF-β1, TGF-β2, TGF-β3, BMP-2, BMP-3, BMP-4, BMP-5, BMP-6, BMP-7, or BMP-9.
5. The composition according to claim 4 , wherein said gene is TGF-β1 or BMP-2.
6. The composition according to claim 1 , wherein said cells are irradiated.
7. The composition according to claim 1 , wherein said cells are mixed with cells that are not transfected or transduced with any DNA.
8. A storage container for storing cells at a temperature of about −70° C. to about −196° C., comprising the composition according to claim 1 .
9. A method of localizing gene expression at a joint space in a mammal, comprising mixing an adhesive effective amount of buffy coat with therapeutic somatic fibroblast or chondrocyte cells to form a composition, wherein said cells are autologous, syngeneic, or allogeneic with respect to said mammal, and administering the composition to the site in need thereof.
10. The method according to claim 9 , wherein said somatic cells are transfected or transduced with a recombinant vector comprising a therapeutic gene.
11. The method according to claim 10 , wherein said therapeutic gene is transforming growth factor β (TGF-β) or bone morphogenetic protein (BMP).
12. The method according to claim 11 , wherein said gene is TGF-β1, TGF-β2,TGF-β3, BMP-2, BMP-3, BMP-4, BMP-5, BMP-6, or BMP-7.
13. The method according to claim 12 , wherein said gene is TGF-β1 or BMP -2.
14. The method according to claim 9 , wherein said cells are irradiated.
15. The method according to claim 9 , wherein the cells are syngeneic with respect to the host recipient.
16. The method according to claim 9 , wherein said somatic cells comprise a mixture of a first type of cells that are transfected or transduced with DNA encoding a therapeutic gene, and a second type of cells that are not transfected or transduced with DNA encoding a therapeutic gene.
17. The method of claim 9 , wherein said cells are stored prior to transplantation.
18. The method of claim 17 , wherein said cells are stored in a cryopreservative prior to transplantation.
19. The method of claim 10 , wherein said transfection or transduction is accomplished by liposome encapsulation, calcium phosphate coprecipitation, electroporation, DEAE—dextran mediation or viral mediation.
20. A method of generating hyaline cartilage in a mammal comprising:
injecting a composition according to claim 3
into a joint space of a mammal such that expression of the cytokine within the joint space generates hyaline cartilage in the joint space.
21. The method according to claim 20 , wherein said cytokine is TGF-β1, TGF-β2, TGF-β3, BMP-2, BMP-3, BMP-4, BMP-5, BMP-6, BMP-7, or BMP-9.
22. The method according to claim 20 , further comprising:
injecting, with said composition,a population of fibroblast or chondrocyte cells that have not been transfected or transduced with a gene encoding TGF-β or BMP.
23. The method according to claim 22 , wherein said composition expresses a cytokine selected from TGF-β1, TGF-β2, TGF-β3, BMP-2, BMP-3, BMP-4, BMP-5, BMP-6, BMP-7, or BMP-9.
24. A method of treating osteoarthritis comprising:
injecting a composition according to claim 3
into a joint space of a mammal such that expression of the cytokine within the joint space generates bone and cartilage in the joint space.
25. The method according to claim 24 , wherein said cytokine is TGF-β1, TGF-β2, TGF-β3, BMP-2, BMP-3, BMP-4, BMP-5, BMP-6, BMP-7, or BMP-9.
26. The method according to claim 24 , further comprising:
injecting, with said composition, a population of fibroblast or chondrocyte cells that have not been transfected or transduced with a gene encoding TGF-β or BMP.
27. The method according to claim 26 , wherein said composition expresses a cytokine selected from TGF-β1, TGF-β2, TGF-β3, BMP-2, BMP-3,BMP-4, BMP-5, BMP-6, BMP-7, or BMP-9.