Use of adipose tissue-derived stromal stem cells in treating fistula
Provided herein are novel methods and compositions utilizing adipose tissue-derived stromal stem cells for treating fistulae.
1. A method of treating a fistula in a subject, comprising delivering a population of cells comprising adipose tissue-derived stromal cells to the subject, wherein less than 5% of the cells in the population express the CD34 marker.
2. The method of claim 1 , wherein the population comprises at least 10×10 6 adipose tissue-derived stromal cells.
3. The method of claim 1 , wherein the adipose tissue-derived stromal cells are allogeneic to the subject.
4. The method of claim 1 , wherein at least 50% of the cells in the population express the CD44 marker.
5. The method of claim 1 further comprising deep scraping of the fistula prior to delivering the adipose derived tissue-derived stromal cells and filling said fistula with an adhesive before, during or after delivering the population of cells.
6. The method of claim 5 , wherein the population comprises at least 10×10 6 adipose tissue-derived stromal cells that are mixed with the adhesive before delivering the population of cells.
7. The method of claim 5 , wherein said adhesive is a fibrin glue or gel.
8. The method of claim 5 , wherein at least 50% of the cells in the composition express the CD44 marker.
9. The method of claim 1 , wherein said method further comprises: delivering a second dose of at least 20×10 6 adipose tissue-derived stromal cells.
10. The method of claim 1 , wherein the population comprises at least 20×10 6 adipose tissue-derived stromal cells.
11. The method of claim 10 , wherein said method further comprises: delivering a second dose of at least 40×10 6 adipose tissue-derived stromal cells.
12. The method of claim 1 , wherein the fistula is selected from the group consisting of an anorectal fistula, enteroenteral fistula, enterocutaneous fistula, rectovaginal fistula, vesicovaginal fistula, fistula-in-ano, fecal fistula, arteriovenous fistula, biliary fistula, cervical fistula, craniosinus fistula, enterovaginal, gastric fistula, metroperitoneal fistula perilymph, pulmonary arteriovenous fistula, umbilical fistula, and tracheoesophageal fistula.
13. The method of claim 1 , further comprising administering a therapeutic agent to said subject.
14. The method of claim 13 , wherein said therapeutic agent is administered locally to the fistula.
15. The method of claim 13 , wherein said therapeutic agent is administered systemically to said subject.
16. The method of claim 13 , wherein said therapeutic agent is selected from the group consisting of an anti-inflammatory agent, an immunosuppressive agent, a biological agent, an antibiotic and an antidiarrheal agent.
17. A method of treating a wound in a subject, comprising: (a) closing the wound with a suture and (b) delivering a composition comprising at least 10×10 6 adipose tissue-derived stromal cells to the closed sutured wound, wherein the adipose tissue-derived stromal cells have been passaged at least six times, and wherein less than 5% of the cells in the composition express the CD34 marker.
18. The method of claim 17 , wherein at least 50% of the cells in the composition express the CD44 marker.
19. The method according to claim 17 , wherein the wound is a fistula selected from the group consisting of anorectal fistula, enterorectal fistula, enterocutaneous fistula, rectovaginal fistula and vesicovaginal fistula.
20. A method of treating a fistula in a subject comprising the steps of:
(i) deep scraping of at least one fistula track
(ii) closing the internal hole of the scraped track with a suture
(iii) delivering a composition comprising at least 10×10 6 adipose tissue-derived stromal cells to the closed sutured internal hole, wherein less than 5% of the cells in the composition express the CD34 marker.
21. A method of treating a fistula in a subject, comprising delivering a population of cells comprising adipose tissue-derived stromal cells to the subject, wherein the adipose tissue-derived stromal cells are allogeneic to the subject, and wherein less than 5% of the cells in the population express the CD34 marker.
22. The method of claim 21 , wherein the population comprises at least 10×10 6 adipose tissue-derived stromal cells.
23. The method of claim 21 , wherein the adipose tissue-derived stromal cells have been passaged at least six times.
24. The method of claim 21 , wherein less than 5% of the cells in the population express the CD34 marker.
25. The method of claim 24 , wherein at least 50% of the cells in the population express the CD44 marker.
26. The method of claim 21 further comprising deep scraping of the fistula prior to delivering the adipose derived tissue-derived stromal cells and filling said fistula with an adhesive before, during or after delivering the population of cells.
27. The method of claim 26 , wherein the population comprises at least 10×10 6 adipose tissue-derived stromal cells that are mixed with the adhesive before delivering the population of cells.
28. The method of claim 26 , wherein said adhesive is a fibrin glue or gel.
29. The method of claim 26 , wherein said adhesive further comprises a composition comprising adipose tissue-derived stromal cells, wherein less than 5% of the cells in the composition express the CD34 marker.
30. The method of claim 29 , wherein at least 50% of the cells in the composition express the CD44 marker.
31. The method of claim 21 , wherein said method further comprises: delivering a second dose of at least 20×10 6 adipose tissue-derived stromal cells.
32. The method of claim 21 , wherein the population comprises at least 20×10 6 adipose tissue-derived stromal cells.
33. The method of claim 32 , wherein said method further comprises: delivering a second dose of at least 40×10 6 adipose tissue-derived stromal cells.
34. The method of claim 21 , wherein the fistula is selected from the group consisting of an anorectal fistula, enteroenteral fistula, enterocutaneous fistula, rectovaginal fistula, vesicovaginal fistula, fistula-in-ano, fecal fistula, arteriovenous fistula, biliary fistula, cervical fistula, craniosinus fistula, enterovaginal, gastric fistula, metroperitoneal fistula perilymph, pulmonary arteriovenous fistula, umbilical fistula, and tracheoesophageal fistula.
35. The method of claim 21 , further comprising administering a therapeutic agent to said subject.
36. The method of claim 35 , wherein said therapeutic agent is administered locally to the fistula.
37. The method of claim 35 , wherein said therapeutic agent is administered systemically to said subject.
38. The method of claim 35 , wherein said therapeutic agent is selected from the group consisting of an anti-inflammatory agent, an immunosuppressive agent, a biological agent, an antibiotic and an antidiarrheal agent.
39. A method of treating a wound in a subject, comprising: (a) closing the wound with a suture and (b) delivering a composition comprising at least 10×10 6 adipose tissue-derived stromal cells to the closed sutured wound, wherein the adipose tissue-derived stromal cells are allogeneic to the subject, and wherein less than 5% of the cells in the population express the CD34 marker.
40. The method of claim 39 , wherein less than 5% of the cells in the composition express the CD34 marker.
41. The method of claim 40 , wherein at least 50% of the cells in the composition express the CD44 marker.
42. The method according to claim 39 , wherein the wound is a fistula selected from the group consisting of anorectal fistula, enterorectal fistula, enterocutaneous fistula, rectovaginal fistula and vesicovaginal fistula.
43. A method of treating a fistula in a subject comprising the steps of:
(i) deep scraping of at least one fistula track
(ii) closing the internal hole of the scraped track with a suture
(iii) delivering composition comprising at least 10×10 6 adipose tissue-derived stromal cells to the closed sutured internal hole, wherein the adipose tissue-derived stromal cells are allogeneic to the subject, and wherein less than 5% of the cells in the population express the CD34 marker.