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Long Term Stem Cell Triumph in the Treatment of Crohn’s Side Effect

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Review of “Long-Term Results of Adipose-Derived Stem Cell Therapy for the Treatment of Crohn’s Fistula” from Stem Cells TM by Stuart P. Atkinson

Crohn’s disease is associated with chronic inflammation of the gastrointestinal tract which can extend through the intestinal wall to create an abnormal connection known as a fistula. Fistula appearance can lead to a decrease in quality of life, frequently recurs [1], and often requires invasive surgery to remove the affected region [2]. However, surgical intervention carries problems of short term efficacy and high recurrence rates and so other more effective treatments are sought after. Researchers have suggested stem cell treatment as a potentially effective alternative, and previous phase I and II clinical trials have found that autologous mesenchymal stem cells derived from adipose tissue (ASCs) demonstrated favorable efficacy and complete healing in 82% of the patients [3, 4]. Now, the laboratory of Chang Sik Yu (University of Ulsan College of Medicine and Asan Medical Center, Korea) report on the long-term outcomes of ASC treatment for Crohn’s fistula [5].

The initial phase II study included 43 patients of both sexes, who had a mixture of trans-sphincteric, extrasphincteric, and suprasphincteric fistula types, with 41 patients included in the intention-to-treat (ITT) analysis. Each patient received an average number of 16.4 x 107 ASCs, and 33 patients had reached the completion of the primary endpoint at 8 weeks (modified Per Protocol - mPP). The ASCs utilized derived from lipoaspirates of each patient’s subcutaneous fat tissue which had been subculture to passage 3-4 in the presence of FGF in order to generate sufficient cell numbers for transplantation. Furthermore, the ASC numbers received by each patient was set according to the size of their specific fistula. The adjoining figure gives an overview of the patient’s analyses. Studying the effects of ASC treatment at 1 year and two years found that 9.3% and 80.8% of the patients in the mPP analysis showed complete fistula healing respectively, while 80.0% and 75.0% of the patients in the modified TT analysis showed complete fistula healing respectively. Overall, 9% of patients only presented with an incomplete response at 24 months. At 8 weeks, 27 patients already had complete closure of the fistula, and of the 24 patients, only 4 presented with a recurrence, 3 of which within a year. Additionally, the analyses found no adverse side-effects associated with ASC administration, which together with the previous data, suggests that strategy represents a safe and effective therapeutic option for Crohn’s fistulae.

These promising findings are an improvement on that observed in previous assessments of ASCs [6, 7] which the authors suggest are due to a number of differences. The two previous studies concentrated mainly on complex cryptoglandular fistulae, used a fixed ASC dosage, and did not use FGF in the cell amplification step. The high levels of closure and the low recurrence rate reported here now suggest that ASC injection is an excellent novel alternative to surgery, and may be the treatment breakthrough that Crohn’s fistulae sufferers have been waiting for.

References

  1. Sangwan YP, Schoetz DJ, Jr., Murray JJ, et al. Perianal Crohn's disease. Results of local surgical treatment. Dis Colon Rectum 1996;39:529-535.
  2. Sandborn WJ, Fazio VW, Feagan BG, et al. AGA technical review on perianal Crohn's disease. Gastroenterology 2003;125:1508-1530.
  3. Lee WY, Park KJ, Cho YB, et al. Autologous adipose tissue-derived stem cells treatment demonstrated favorable and sustainable therapeutic effect for Crohn's fistula. Stem Cells 2013;31:2575-2581.
  4. Cho YB, Lee WY, Park KJ, et al. Autologous adipose tissue-derived stem cells for the treatment of Crohn's fistula: a phase I clinical study. Cell transplantation 2013;22:279-285.
  5. Cho YB, Park KJ, Yoon SN, et al. Long-term results of adipose-derived stem cell therapy for the treatment of Crohn's fistula. Stem Cells Translational Medicine 2015;4:532-537.
  6. Garcia-Olmo D, Herreros D, Pascual I, et al. Expanded adipose-derived stem cells for the treatment of complex perianal fistula: a phase II clinical trial. Dis Colon Rectum 2009;52:79-86.
  7. 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 2012;27:595-600.