Skip to main content
Log in

Long-term follow-up of patients undergoing adipose-derived adult stem cell administration to treat complex perianal fistulas

  • Original Article
  • Published:
International Journal of Colorectal Disease Aims and scope Submit manuscript

Abstract

Purpose

In patients with perianal fistulas, administration of adult stem cells (ASCs) derived from liposuction samples has proved a promising technique in a preceding phase II trial. We aimed to extend follow-up of these patients with this retrospective study.

Method

Patients who had received at least one dose of treatment (ASCs plus fibrin glue or fibrin glue alone) were included. Adverse events notified since the end of the phase II study were recorded. Clinical and magnetic resonance imaging (MRI) criteria were used to determine whether recurrence of the healed fistula had occurred.

Results

Data were available for 21 out of 24 patients treated with ASCs plus fibrin glue and 13 out of 25 patients treated with fibrin glue in the phase II study. Follow-up lasted a mean of 38.0 and 42.6 months, respectively. Two adverse events unrelated to the original treatment were reported, one in each group. There were no reports of anal incontinence associated with the procedure. Of the 12 patients treated with ASCs plus fibrin glue who were included in the retrospective follow-up in the complete closure group, only 7 remained free of recurrence. MRI was done in 31 patients. No relationship was detected between MRI results and the clinical fistula status, independent of the treatment received.

Conclusions

Long-term follow-up reaffirmed the very good safety profile of the treatment. Nevertheless, a low proportion of the stem cell-treated patients with closure after the procedure remained free of recurrence after more than 3 years of follow-up.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. García-Olmo D, García-Arranz M, García LG, Cuellar ES, Blanco IF, Prianes LA et al (2003) Autologous stem cell transplantation for treatment of rectovaginal fistula in perianal Crohn’s disease: a new cell-based therapy. Int J Colorectal Dis 18(5):451–454

    Article  PubMed  Google Scholar 

  2. García-Olmo D, García-Arranz M, Herreros D, Pascual I, Peiro C, Rodríguez-Montes JA (2005) A phase I clinical trial of the treatment of Crohn’s fistula by adipose mesenchymal stem cell transplantation. Dis Colon Rectum 48(7):1416–1423

    Article  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  4. Silverberg MS, Satsangi J, Ahmad T, Arnott ID, Bernstein CN, Brant SR et al (2005) Toward an integrated clinical, molecular and serological classification of inflammatory bowel disease: report of a Working Party of the 2005 Montreal World Congress of Gastroenterology. Can J Gastroenterol 19(Suppl A):5–36

    PubMed  Google Scholar 

  5. Gimble J, Guilak F (2003) Adipose-derived adult stem cells: isolation, characterization, and differentiation potential. Cytotherapy 5(5):362–369

    Article  PubMed  Google Scholar 

  6. van Koperen PJ, Wind J, Bemelman WA, Bakx R, Reitsma JB, Slors JFM (2008) Long-term functional outcome and risk factors for recurrence after surgical treatment for low and high perianal fistulas of cryptoglandular origin. Dis Colon Rectum 51(10):1475–1481

    Article  PubMed  Google Scholar 

  7. Present DH, Rutgeerts P, Targan S, Hanauer SB, Mayer L, van Hogezand RA et al (1999) Infliximab for the treatment of fistulas in patients with Crohn’s disease. N Engl J Med 340(18):1398–1405

    Article  PubMed  CAS  Google Scholar 

  8. Parsi MA, Lashner BA (2004) Safety of infliximab: primum non nocere. The safety profile of infliximab in patients with Crohn’s disease: the Mayo Clinic experience in 500 patients. Inflamm Bowel Dis 10(4):486–487

    Article  PubMed  Google Scholar 

  9. Lindsey I, Smilgin-Humphreys MM, Cunningham C, Mortensen NJM, George BD (2002) A randomized, controlled trial of fibrin glue vs. conventional treatment for anal fistula. Dis Colon Rectum 45(12):1608–1615

    Article  PubMed  Google Scholar 

  10. Sands BE, Blank MA, Patel K, van Deventer SJ (2004) Long-term treatment of rectovaginal fistulas in Crohn’s disease: response to infliximab in the ACCENT II Study. Clin Gastroenterol Hepatol 2(10):912–920

    Article  PubMed  CAS  Google Scholar 

  11. Gurudu SR, Griffel LH, Gialanella RJ, Das KM (1999) Cyclosporine therapy in inflammatory bowel disease: short-term and long-term results. J Clin Gastroenterol 29(2):151–154

    Article  PubMed  CAS  Google Scholar 

  12. Cintron JR, Park JJ, Orsay CP, Pearl RK, Nelson RL, Sone JH et al (2000) Repair of fistulas-in-ano using fibrin adhesive: long-term follow-up. Dis Colon Rectum 43(7):944–949, discussion 949–950

    Article  PubMed  CAS  Google Scholar 

  13. Levy C, Tremaine WJ (2002) Management of internal fistulas in Crohn’s disease. Inflamm Bowel Dis 8(2):106–111

    Article  PubMed  Google Scholar 

  14. González MA, Gonzalez-Rey E, Rico L, Büscher D, Delgado M (2009) Adipose-derived mesenchymal stem cells alleviate experimental colitis by inhibiting inflammatory and autoimmune responses. Gastroenterol 136(3):978–989

    Article  Google Scholar 

  15. Sahni VA, Ahmad R, Burling D (2008) Which method is best for imaging of perianal fistula? Abdom Imaging 33(1):26–30

    Article  PubMed  Google Scholar 

  16. Tougeron D, Savoye G, Savoye-Collet C, Koning E, Michot F, Lerebours E (2009) Predicting factors of fistula healing and clinical remission after infliximab-based combined therapy for perianal fistulizing Crohn’s disease. Dig Dis Sci 54(8):1746–1752

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors thank the following colleagues for their invaluable help during the course of this study: Dr. José Antonio Pascual, M.D. (Department. of Surgery, Doce de Octubre University Hospital, Madrid, Spain), Dr. Emilio Del-Valle, M.D., and Dr. Jaime Zorrilla, M.D. (Department of Surgery, Gregorio Marañón University Hospital, Madrid, Spain) for their assistance in the patient follow-up; Dr. Jorge Alemany, Dr. Maria Pascual, and Dr. Gemma Fernandez (Cellerix S.A., Madrid) for their contribution to the initial design; and Dr. Gregory Morley for the editorial support.

Financial disclosure and conflicts of interest

This clinical trial has been sponsored by Cellerix S.L. Damian García-Olmo is a holder of the UAM–Cellerix Chair of Cell Therapy and Regenerative Medicine to which Cellerix contributes 40,000€ per year. UAM and Cellerix S.A. share patent rights to Cx401. García-Olmo is a member of the advisory board of Cellerix S.A. M. Garcia-Arranz and D. García-Olmo are inventors in two patents related to Cx401 entitled “Identification and isolation of multipotent cells from non-osteochondral mesenchymal tissue” (10157355957US) and “Use of adipose tissue-derived stromal stem cells in treating fistula” (US11/167061).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Hector Guadalajara.

Additional information

The European Medicines Agency (EMA) granted Cx401 (autologous expanded adipose-derived adult stem cells—eASCs) “orphan drug” status in 2005 for the treatment of anal fistula (Orphan Designation EU Number EU/3/05/303).

This is a randomized clinical trial.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Guadalajara, H., Herreros, D., De-La-Quintana, P. et al. Long-term follow-up of patients undergoing adipose-derived adult stem cell administration to treat complex perianal fistulas. Int J Colorectal Dis 27, 595–600 (2012). https://doi.org/10.1007/s00384-011-1350-1

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00384-011-1350-1

Keywords

Navigation