Adipose tissue-derived stromal stem cells for use in treating refractory complex perianal fistulas in Crohn's disease

1. A method of treating a refractory complex perianal fistula in a subject having Crohn's disease comprising administering a therapeutic amount of a population of expanded allogeneic adipose tissue-derived stromal stem cells to the subject, wherein:

(i) the fistula comprises multiple tracts;

(ii) a fixed dose of about 120 million expanded allogeneic adipose tissue-derived stromal stem cells is administered to the subject in a single procedure, wherein each fistula tract receives at least a proportion of this dose and wherein approximately half of the dose is injected into the tissue surrounding the internal opening or openings and the other half is injected into the fistula walls all along the fistula tracts; and

(iii) the administration of the therapeutic amount of the population of expanded allogeneic adipose tissue-derived stromal stem cells induces combined remission within 24 weeks that is statistically superior to placebo.

2. The method according to claim 1 , wherein the fistula comprises 2 internal openings.

3. The method according to claim 1 , wherein the fistula comprises 2 or 3 external openings.

4. The method according to claim 1 , wherein the administering a therapeutic amount of a population of expanded allogeneic adipose tissue-derived stromal stem cells to the subject induces clinical remission within 6 weeks.

5. The method according to claim 1 , wherein the administering a therapeutic amount of a population of expanded allogeneic adipose tissue-derived stromal stem cells induces combined remission within 18 weeks that is statistically superior to placebo.

6. The method according to claim 1 , wherein an improvement in perianal disease activity index (PDAI) is achieved within 24 weeks.

7. The method according to claim 6 , wherein the improvement in PDAI is an improvement of greater than 1.5 PDAI points.

8. The method according to claim 6 , wherein the improvement in PDAI is an improvement of at least two PDAI points.

9. The method according to claim 1 , wherein the fistula is refractive to (i) antibiotic, (ii) immunosuppressant, (iii) anti-TNF therapy, or (iv) any combination thereof.

10. The method according to claim 1 , wherein the subject receives neither or both of an anti-TNF therapy and immunosuppressant therapy.

11. The method according to claim 1 , wherein the subject has:

(a) non-active or mildly active Crohn's disease;

(b) luminal Crohn's disease; or

(c) both (a) and (b).

12. The method according to claim 1 , wherein the fistula is monitored by magnetic resonance imaging (MRI).

13. The method according to claim 1 , wherein the expanded allogeneic adipose tissue-derived stromal stem cells express four or more of HLAI, CD29, CD44, CD59, CD73, CD90, and CD105; and do not express four or more of HLAII, CD11b, CD11c, CD14, CD45, CD31, CD34, and CD80.

14. The method according to claim 1 , wherein the administering a therapeutic amount of a population of expanded allogeneic adipose tissue-derived stromal stem cells to the subject induces clinical remission within 8 weeks.

15. The method according to claim 14 , wherein the clinical remission is sustained through to 24 weeks from the administering a therapeutic amount of a population of expanded allogeneic adipose tissue-derived stromal stem cells to the subject.

16. The method according to claim 1 , wherein the administering a therapeutic amount of a population of expanded allogeneic adipose tissue-derived stromal stem cells induces combined remission within 12 weeks that is statistically superior to placebo.

17. The method according to claim 1 , wherein the administering a therapeutic amount of a population of expanded allogeneic adipose tissue-derived stromal stem cells induces combined remission within 10 weeks that is statistically superior to placebo.

18. The method according to claim 1 , wherein an improvement in perianal disease activity index (PDAI) is achieved within 18 weeks.

19. The method according to claim 1 , wherein an improvement in perianal disease activity index (PDAI) is achieved within 12 weeks.

20. The method according to claim 1 , wherein an improvement in perianal disease activity index (PDAI) is achieved within 10 weeks.