A Phase I Clinical Trial of the Treatment of Crohn’s Fistula by Adipose Mesenchymal Stem Cell Transplantation (original) (raw)

PURPOSE

The effective management of fistulas in patients with Crohn’s disease presents an extremely challenging problem. Mesenchymal adult stem cells extracted from certain tissues, such as adipose tissue, can differentiate into various cell types. Therefore, we have tried to use such cells to stimulate healing of Crohn’s fistulas.

METHODS

We designed a prospective Phase I clinical trial, involving five patients with Crohn’s disease, to test the feasibility and safety of autologous stem cells transplantation in the treatment of fistulas. We also studied the expression of various cell markers and the growth rates of the lipoaspirate-derived cells that were used for transplantation.

RESULTS

One patient was excluded because of bacterial contamination of cultured cells. We inoculated nine fistulas in four patients with autologous adipose tissue-derived stem cells at Passage 3 or earlier. Eight inoculated fistulas were followed weekly for at least eight weeks. In six fistulas, the external opening was covered with epithelium at the end of Week 8, and, thus, these fistulas were considered healed (75 percent). In the other two fistulas, there was only incomplete closure of the external opening, with a decrease in output flow (not healed; 25 percent). No adverse effects were observed in any patient at the end of the follow-up period (minimum follow-up,12 months; maximum follow-up, 30 months; follow-up average, 22 months).

CONCLUSIONS

To our knowledge, this is the first report of a clinical trial of cell therapy using autologous stem cells obtained from a lipoaspirate. Our results indicate that our protocol is feasible and safe for the treatment of fistulas in Crohn’s disease. The number of patients included and the uncontrolled nature of Phase I clinical trials do not allow demonstration of the effectiveness of the treatment. However, the results of the present study encourage to perform further studies in Phase II.

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ACKNOWLEDGMENTS

The authors thank Dolores Garcia-Olmo, Ph.D., Chief of the Research Unit, (Albacete General Hospital-Spain) and Paloma De-La-Quintana, stomatherapist nurse (La Paz University Hospital-Madrid-Spain), for their useful collaboration during the development of this study, and C. F. Sánchez-Ferrer, Department of Pharmacology (U.A.M.), for providing us with the room and part of the material to perform some of the indirect immunofluorescence assays.

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Authors and Affiliations

  1. Department of General Surgery, “La Paz” University Hospital, Madrid, Spain
    Damián García-Olmo M.D., Dolores Herreros M.D., Isabel Pascual M.D. & José Antonio Rodríguez-Montes M.D.
  2. Cell Therapy Laboratory, “La Paz” University Hospital, Madrid, Spain
    Damián García-Olmo M.D., Mariano García-Arranz Ph.D., Dolores Herreros M.D. & Isabel Pascual M.D.
  3. Department of Surgery, Universidad Autónoma de Madrid, Madrid, Spain
    Damián García-Olmo M.D. & José Antonio Rodríguez-Montes M.D.
  4. Department of Pharmacology and Therapeutics, “La Paz” University Hospital, Madrid, Spain
    Concepción Peiro Ph.D.

Authors

  1. Damián García-Olmo M.D.
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  2. Mariano García-Arranz Ph.D.
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  3. Dolores Herreros M.D.
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  4. Isabel Pascual M.D.
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  5. Concepción Peiro Ph.D.
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  6. José Antonio Rodríguez-Montes M.D.
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Corresponding author

Correspondence toDamián García-Olmo M.D..

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García-Olmo, D., García-Arranz, M., Herreros, D. et al. A Phase I Clinical Trial of the Treatment of Crohn’s Fistula by Adipose Mesenchymal Stem Cell Transplantation.Dis Colon Rectum 48, 1416–1423 (2005). https://doi.org/10.1007/s10350-005-0052-6

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