Use of adipose tissue-derived stromal stem cells in treating fistula

Abstract

Provided herein are novel methods and compositions utilizing adipose tissue-derived stromal stem cells for treating fistulae.

1 . A adipose tissue-derived stromal stem cell-containing composition, wherein at least about 50% of the adipose tissue-derived stromal stem cells comprising the composition express the CD9, CD10, CD13, CD29, CD44, CD49A, CD51, CD54, CD55, CD58, CD59 CD90 and CD105 markers.  
     
     
         2 . The adipose tissue-derived stromal stem cell-containing composition of  claim 1 , wherein at least about 85% of the adipose tissue-derived stromal stem cells comprising the composition express the CD9, CD10, CD13, CD29, CD44, CD49A, CD51, CD54, CD55, CD58, CD59 CD90 and CD105 markers.  
     
     
         3 . The adipose tissue-derived stromal stem cell-containing composition of  claim 2 , wherein at least about 95% of the adipose tissue-derived stromal stem cells comprising the composition express the CD9, CD10, CD13, CD29, CD44, CD49A, CD51, CD54, CD55, CD58, CD59 CD90 and CD105 markers.  
     
     
         4 . The adipose tissue-derived stromal stem cell-containing composition of  claim 3 , wherein at least about 99% of the adipose tissue-derived stromal stem cells comprising the composition express the CD9, CD10, CD13, CD29, CD44, CD49A, CD51, CD54, CD55, CD58, CD59 CD90 and CD105 markers.  
     
     
         5 . The adipose tissue-derived stromal stem cell-containing composition of  claim 4 , wherein fewer than about 5% of the adipose tissue-derived stromal stem cells comprising the composition express the CD34 CD11b, CD14, CD15, CD16, CD31, CD34, CD45, CD49f, CD102, CD104, CD106 and/or CD133 markers.  
     
     
         6 . The adipose tissue-derived stromal stem cell-containing composition of  claim 1 , further comprising Ringer's solution and HSA.  
     
     
         7 . The adipose tissue-derived stromal stem cell-containing composition of  claim 6 , wherein the concentration of the adipose tissue-derived stromal stem cells comprising the composition is at least about 10×10 6  cells/mL.  
     
     
         8 . The adipose tissue-derived stromal stem cell-containing composition of  claim 7 , wherein the concentration of the adipose tissue-derived stromal stem cells comprising the composition is at least about 20×10 6  cells/mL.  
     
     
         9 . The adipose tissue-derived stromal stem cell-containing composition of  claim 1 , further comprising an adhesive.  
     
     
         10 . The adipose tissue-derived stromal stem cell-containing composition of  claim 9 , wherein said adhesive is a fibrin glue or gel.  
     
     
         11 . A support comprising an adipose tissue-derived stromal stem cell-containing composition of  claim 1 .  
     
     
         12 . The support of  claim 11 , wherein said support is a suture.  
     
     
         13 . The support of  claim 11 , wherein said support is a patch.  
     
     
         14 . A method of preparing an adipose tissue-derived stromal stem cell-containing composition of  claim 1 , comprising: (a) collecting adipose tissue from a subject; (b) obtaining a cell suspension by enzymatic digestion; (c) sedimenting the cell suspension and resuspending the adipose tissue-derived stromal stem cells in a culture medium; (d) culturing of the adipose tissue-derived stromal stem cells for at least about 10 days; and (g) passaging the adipose tissue-derived stromal stem cells at least two times.  
     
     
         15 . The method of  claim 14 , wherein the adipose tissue-derived stromal stem cells are cultured for at least 20 days.  
     
     
         16 . The method of  claim 14 , comprising passaging the adipose tissue-derived stromal stem cells at least three times.  
     
     
         17 . A method of preparing an adhesive for fistula repair, comprising suspending an adipose tissue-derived stromal stem cell-containing composition of  claim 1  with a fibrin-based polymer.  
     
     
         18 . A method of treating a fistula in a subject, comprising: (a) closing the internal hole with a suture and (b) delivering at least about 10×10 6  adipose tissue-derived stromal stem cells to the closed sutured internal hole.  
     
     
         19 . The method of  claim 18 , wherein the adipose tissue-derived stromal stem cells comprise an adipose tissue-derived stromal stem cell-containing composition of  claim 1 .  
     
     
         20 . The method of  claim 18 , further comprising: (d) deep scraping of at least one fistula track; (e) filling said fistula track with an adhesive.  
     
     
         21 . The method of  claim 20 , further comprising: (f) delivering a at least about 10×10 6  adipose tissue-derived stromal stem cells to the adhesive.  
     
     
         22 . The method of  claim 20 , wherein said adhesive is a fibrin glue or gel.  
     
     
         23 . The method of  claim 21 , wherein said adhesive further comprises an adipose tissue-derived stromal stem cell-containing composition of  claim 1 .  
     
     
         24 . The method of  claim 18 , wherein said method further comprises: (c) delivering a second dose of at least about 20×10 6  adipose tissue-derived stromal stem cells.  
     
     
         25 . The method of  claim 18 , wherein said method comprises delivering at least about 20×10 6  adipose tissue-derived stromal stem cells.  
     
     
         26 . The method of  claim 25 , wherein said method further comprises: (c) delivering a second dose of at least about 40×10 6  adipose tissue-derived stromal stem cells.  
     
     
         27 . The method of  claim 18 , wherein the adipose tissue-derived stromal stem cells are derived from the adipose tissue of the subject.  
     
     
         28 . The method of  claim 18 , wherein the fistula is an anorectal, enteroenteral, enterocutaneous, rectovaginal or vesicovaginal fistula.  
     
     
         29 . The method of  claim 18 , further comprising administering a therapeutic agent to said subject.  
     
     
         30 . The method of  claim 29 , wherein said therapeutic agent is administered locally to the closed sutured internal hole.  
     
     
         31 . The method of  claim 30 , wherein said therapeutic agent is administered systemically to said subject.  
     
     
         32 . A method of treating a wound in a subject, comprising: (a) closing the wound with a suture and (b) delivering at least about 10×10 6  adipose tissue-derived stromal stem cells to the closed sutured wound.  
     
     
         33 . The method of  claim 23 , wherein the adipose tissue-derived stromal stem cells comprise a cellular composition of  claim 1 .  
     
     
         34 . An adipose tissue-derived stromal stem cell that expresses the c-Kit, vimentin and CD90 markers and does not express the CD34, Factor VIII, alpha-actin, desmin, S-100 and keratin markers.  
     
     
         35 . An adipose tissue-derived stromal stem cell that expresses the CD9, CD10, CD13, CD29, CD44, CD49A, CD51, CD54, CD55, CD58, CD59 CD90 and CD105 markers and does not express the CD34 CD11b, CD14, CD15, CD16, CD31, CD34, CD45, CD49f, CD102, CD104, CD106 and/or CD133 markers.