Autologous bone marrow derived stem cells in the treatment of complex anal fistula

Mohamed M. Raslan, Mahmoud A. Ayoub


Background: Treatment of anal fistula shows a great conflict between preservation of continence and eradication of sepsis. Stem cells extracted from bone marrow are able to home to inflamed tissues and repair injured ones. The aim of this study is to present the early results of injection of stem cells to tracts of complex recurrent fistulae. The primary outcome of the study is the healing of the complex fistula secondary outcomes include safety profile of the procedure.

Methods: 15 patients having complex anal fistulae. To prepare stem cells, bone marrow aspiration was performed under complete aseptic conditions. After several steps for isolation, viability testing and preparation, stem cells were suspended in sterile saline for injection in the patients. The internal opening was identified and closed then curettage of the tract with injection of cell suspension simultaneous with fibrin glue followed by injection of stem cell suspension around the tract and external opening finally it was closed. The first evaluation was performed after 8 weeks, a final evaluation after one year.

Results: Categorized into three groups (a) complete healing 8 patients (53.3%). (b) Incomplete healing 4 patients (26.7%) (c) Recurrence 3 patients (20%) No incontinence, abnormal tissue growth or major adverse effects were reported.

Conclusions: Use of autologous bone marrow-derived stem cells in anal fistula treatment is a recent modality with variable rates of success. Despite the rate of failure or incomplete healing but it still provides a solution to avoid continence impairment. It needs better evaluation with larger sample size, with long-term follow up. literatures.


Autologous, Bone marrow, Complex anal fistula, Derived stem cells

Full Text:



Blumetti J, Abcarian A, Quinteros F, Chaudhry V, Prasad L, Abcarian H: Evolution of treatment of fistula in ano. World J. Surg. 2012;36:1162-7.

Westerterp M, Volkers NA, Poolman RW, van Tets WF. Anal fistulotomy between Skylla and Charybdis. Colorectal Dis. 2003;5:549-51.

Cintron J.R., Park J.J., Orsay C.P. et al.: Repair of fistulas-in-ano using fibrin ad¬hesive: long-term follow-up. Dis. Colon Rectum. 2000;43:944-9.

De Parades V, Far HS, Etienney I, Zeitoun JD, Atienza P, Bauer P. Seton drainage and fibrin glue injec¬tion for complex anal fistulas. Colorectal Dis. 2010;12:459-63.

O’Connor L, Champagne BJ, Ferguson MA, Orangio GR, Schertzer ME, Armstrong DN. Efficacy of anal fistula plug in closure of Crohn’s anorectal fistulas. Dis. Colon Rectum. 2006;49: 1569-73.

Garg P, Song J, Bhatia A, Kalia H, Menon GR. The efficacy of anal fistula plug in fistula-in¬-ano: a systematic review. Colorectal Dis. 2010;12:965-70.

Nauta AJ, Fibbe WE. Immunomodulatory properties of mesenchymal stromal cells. Blood 2007;110:3499e506.

Satija NK, Singh VK, Verma YK, Gupta P, Sharma S, Afrin F., et al. Mesenchymal stem cell-based therapy: a new paradigm in regenerative medicine. J Cell Mol Med 2009;13:4385-402.

Keyser K.A., Beagles K.E., Kiem H.P. Comparison of mesenchymal stem cells from different tissues to suppress T-cell activation. Cell Transpl. 2007;16: 555-62.

González MA, Gonzalez–Rey E, Rico L, Büscher D, Delgado M. Adipose-derived mesenchy¬mal stem cells alleviate experimental colitis by inhibiting inflammatory and autoimmune responses. Gastroenterology. 2009; 136: 978-89.

Lee EY, Xia Y, Kim WS, Kim MH, Kim TH, Kim KJ, et al. Hypoxia-enhanced wound-healing function of adipose-derived stem cells: Increase in stem cell proliferation and up-regulation of VEGF and bFGF. Wound Repair Regen. 2009;17:540-7.

Kim WS, Park BS, Sung JH, Yang JM, Park SB, Kwak SJ, et al.: Wound healing effect of adipose-derived stem cells: a critical role of secretory factors on human dermal fibroblasts. J. Dermatol. Sci. 2007;48:15-24.

Zuk PA, Zhu M, Mizuno H, Huang J, Futrell JW et al.: Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Eng. 2001;7:211-28.

Parks AG, Gordon PH, Hardcastle JD. A classification of fistula in-ano. Br J Surg 1976; 63: 1-12.

Whiteford MH, Kilkenny J, Hyman N, Buie WD, Cohen J, Orsay C. et al. Practice parameters for the treatment of perianal abscess and fistula-in ano (revised). Dis Colon Rectum 2005;48:1337-42.

Jorge, J. MN,Wexner, SD. Etiology and management of fecal incontinence. Dis Colon Rect./ 1993l;36:77-97.

Patrlj L, Kocman B, Martinac M, Jadrijevic S, Sosa T, Sebecic B, Brkljacic B. Fibrin glue-antibiotic mixture in the treatment of anal fistulae: experience with 69 cases. Dig Surg. 2000;17:77-80.

Buchanan GN, Bartram CI, Phillips RK, Gould SW, Halligan S, Rockall TA, Sibbons P, Cohen RG. Efficacy of fibrin sealant in the management of complex anal fistula: a prospective trial. Dis Colon Rectum 2003;46:1167-74.

Herreros MD, Garcia-Arranz M, Guadalajara H, De-La-Quintana P, Garcia-Olmo D. et al.: Autologous expanded adipose-derived stem cells for the treatment of complex cryptoglandular perianal fistulas: a phase III randomized clinical trial (FATT 1: fistula Advanced Therapy Trial 1) and long-term evaluation. Dis. Colon Rectum. 2012;55:762-72.

Garcia-Olmo D, Guadalajara H, Rubio-Perez I, Herreros MD, de-la-Quintana P, Garcia-Arranz M. Recurrent anal fistulae: limited surgery supported by stem cells. World J. Gastroenterol. 2015;21:3330-6.

Singer NG, Caplan AI. Mesenchymal stem cells: mechanisms of inflammation. Annu Rev Pathol 2011;6:457-78.

Garcia-Olmo D, Herreros D, Pascual I, Pascual JA, Del-Valle E, Zorrilla J. et al., Expanded adipose-derived stem cells for the treatment of complex perianal fistula: a phase II clinical trial. Dis Colon Rectum. 2009 Jan;52(1):79-86.

Zuk PA, Zhu M, Ashjian P, De Ugarte DA, Huang JI, Mizuno H., et al. Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell 2002;13:4279-95.

Gimble J, Guilak F. Adipose-derived adult stem cells: isolation, characterization, and differentiation potential. Cytotherapy. 2003;5:362-9.

Guadalajara H, Herreros D, De-La-Quintana P, Trebol J, Garcia-Arranz M, Garcia-Olmo D Long-term follow-up of patients undergoing adipose-derived adult stem cell administration to treat complex perianal fistulas. Int J Colorectal Dis. 2012;27:595-600.

Garcia-Olmo D, Garcia-Arranz M, Herreros D. Expanded adipose-derived stem cells for the treatment of complex perianal fistula including Crohn‟s disease. Expert Opin Biol Ther. 2008;9: 1417-23.