278
Views
4
CrossRef citations to date
0
Altmetric
Review

Human mesenchymal stem cell therapy in the management of luminal and perianal fistulizing Crohn’s disease – review of pathomechanism and existing clinical data

ORCID Icon, ORCID Icon, ORCID Icon, ORCID Icon & ORCID Icon
Pages 737-745 | Received 28 Feb 2018, Accepted 20 Jun 2018, Published online: 04 Jul 2018

References

  • Van Assche G, Dignass A, Reinisch W, et al. The second European evidence-based consensus on the diagnosis and management of Crohn’s disease: special situations. J Crohns Colitis. 2010;4(1):63–101.
  • Tang LY, Rawsthorne P, Bernstein CN. Are perineal and luminal fistulas associated in Crohn’s disease? A population-based study. Clin Gastroenterol Hepatol. 2006;4(9):1130–1134.
  • Peyrin-Biroulet L, Loftus EV, Colombel JF, et al. The natural history of adult Crohn’s disease in population-based cohorts. Am J Gastroenterol. 2010;105(2):289–297.
  • Baumgart DC, Sandborn WJ. Crohn’s disease. Lancet. 2012;380(9853):1590–1605.
  • Hanauer SB, Feagan BG, Lichtenstein GR, et al. Maintenance infliximab for Crohn’s disease: the ACCENT I randomised trial. Lancet. 2002;359(9317):1541–1549.
  • Colombel J-F, Sandborn WJ, Rutgeerts P, et al. Adalimumab for maintenance of clinical response and remission in patients with Crohn’s disease: the CHARM trial. Gastroenterology. 2007;132(1):52–65.
  • Molnár T, Farkas K, Nyári T, et al. Frequency and predictors of loss of response to infliximab or adalimumab in Crohn’s disease after one-year treatment period – a single center experience. J Gastrointestin Liver Dis. 2012;21(3):265–269.
  • Bouguen G, Siproudhis L, Gizard E, et al. Long-term outcome of perianal fistulizing Crohn’s disease treated with infliximab. Clin Gastroenterol Hepatol. 2013;11(8):975–981.e1-4.
  • Sands BE, Anderson FH, Bernstein CN, et al. Infliximab maintenance therapy for fistulizing Crohn’s disease. N Engl J Med. 2004;350(9):876–885.
  • Feagan BG, Rutgeerts P, Sands BE, et al. Vedolizumab as induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2013;369(8):699–710.
  • Dothel G, Raschi E, Rimondini R, et al. Mesenchymal stromal cell-based therapy: regulatory and translational aspects in gastroenterology. World J Gastroenterol. 2016;22(41):9057–9068.
  • Friedenstein AJ, Chailakhyan RK, Latsinik NV, et al. Stromal cells responsible for transferring the microenvironment of the hemopoietic tissues. Cloning in vitro and retransplantation in vivo. Transplantation. 1974;17(4):331–340.
  • Friedenstein AJ, Chailakhjan RK, Lalykina KS. The development of fibroblast colonies in monolayer cultures of guinea-pig bone marrow and spleen cells. Cell Tissue Kinet. 1970;3(4):393–403.
  • De Francesco F, Romano M, Zarantonello L, et al. The role of adipose stem cells in inflammatory bowel disease: from biology to novel therapeutic strategies. Cancer Biol Ther. 2016;17(9):889–898.
  • Deans RJ, Moseley AB. Mesenchymal stem cells: biology and potential clinical uses. Exp Hematol. 2000;28(8):875–884.
  • Mao F, Tu Q, Wang L, et al. Mesenchymal stem cells and their therapeutic applications in inflammatory bowel disease. Oncotarget. 2017;8(23):38008–38021.
  • Dominici M, Le Blanc K, Mueller I, et al. Minimal criteria for defining multipotent mesenchymal stromal cells. Int Soc Cell Ther Position Statement. Cytotherapy. 2006;8(4):315–317.
  • Mo M, Wang S, Zhou Y, et al. Mesenchymal stem cell subpopulations: phenotype, property and therapeutic potential. Cell Mol Life Sci. 2016;73(17):3311–3321.
  • García-Gómez I, Elvira G, Zapata AG, et al. Mesenchymal stem cells: biological properties and clinical applications. Expert Opin Biol Ther. 2010;10(10):1453–1468.
  • Tsuchiya A, Kojima Y, Ikarashi S, et al. Clinical trials using mesenchymal stem cells in liver diseases and inflammatory bowel diseases. Inflamm Regen. 2017;37(1):16.
  • Klyushnenkova E, Mosca JD, Zernetkina V, et al. T cell responses to allogeneic human mesenchymal stem cells: immunogenicity, tolerance, and suppression. J Biomed Sci. 2005;12(1):47–57.
  • Le Blanc K, Tammik C, Rosendahl K, et al. HLA expression and immunologic properties of differentiated and undifferentiated mesenchymal stem cells. Exp Hematol. 2003;31(10):890–896.
  • Zangi L, Margalit R, Reich-Zeliger S, et al. Direct imaging of immune rejection and memory induction by allogeneic mesenchymal stromal cells. Stem Cells. 2009;27(11):2865–2874.
  • Zundler S, Neurath MF. Immunopathogenesis of inflammatory bowel diseases: functional role of T cells and T cell homing. Clin Exp Rheumatol. 2015;33(4 Suppl 92):S19–S28.
  • Stefanelli T, Malesci A, Repici A, et al. New insights into inflammatory bowel disease pathophysiology: paving the way for novel therapeutic targets. Curr Drug Targets. 2008;9(5):413–418.
  • Becker F, Yi P, Al-Kofahi M, et al. Lymphatic dysregulation in intestinal inflammation: new insights into inflammatory bowel disease pathomechanisms. Lymphology. 2014;47(1):3–27.
  • He XW, He XS, Lian L, et al. Systemic infusion of bone marrow-derived mesenchymal stem cells for treatment of experimental colitis in mice. Dig Dis Sci. 2012;57(12):3136–3144.
  • González MA, Gonzalez-Rey E, Rico L, et al. Adipose-derived mesenchymal stem cells alleviate experimental colitis by inhibiting inflammatory and autoimmune responses. Gastroenterology. 2009;136(3):978–989.
  • Ren G, Zhang L, Zhao X, et al. Mesenchymal stem cell-mediated immunosuppression occurs via concerted action of chemokines and nitric oxide. Cell Stem Cell. 2008;2(2):141–150.
  • Shi Y, Su J, Roberts AI, et al. How mesenchymal stem cells interact with tissue immune responses. Trends Immunol. 2012;33(3):136–143.
  • Hawkey CJ, Hommes DW. Is stem cell therapy ready for prime time in treatment of inflammatory bowel diseases?. Gastroenterology. 2017;152(2):389–397.e2.
  • Duijvestein M, Vos AC, Roelofs H, et al. Autologous bone marrow-derived mesenchymal stromal cell treatment for refractory luminal Crohn’s disease: results of a phase I study. Gut. 2010;59(12):1662–1669.
  • Forbes GM, Sturm MJ, Leong RW, et al. A phase 2 study of allogeneic mesenchymal stromal cells for luminal Crohn’s disease refractory to biologic therapy. Clin Gastroenterol Hepatol. 2014;12(1):64–71.
  • Dhere T, Copland I, Garcia M, et al. The safety of autologous and metabolically fit bone marrow mesenchymal stromal cells in medically refractory Crohn’s disease – a phase 1 trial with three doses. Aliment Pharmacol Ther. 2016;44(5):471–481.
  • Knyazev O, Kagramanova A, Churikova A, et al. P575 The use of mesenchymal stromal cells in order to achieve deep (biological) remission of ulcerative colitis. J Crohn’s Colitis. 2015;9(suppl 1):S367–S368.
  • Knyazev O, Fadeeva N, Kagramanova A, et al. P485 The combined of mesenchymal stem cells and infliximab reduces the recurrence rate of Crohn’s disease. J Crohn’s Colitis. 2016;10(suppl 1):S346.
  • Zhang J, Lv S, Liu X, et al. Umbilical cord mesenchymal stem cell treatment for Crohn’s disease: a randomized controlled clinical trial. Gut Liver. 2018;12(1):73–78.
  • Bemelman WA, Warusavitarne J, Sampietro GM, et al. ECCO-ESCP consensus on surgery for Crohn’s disease. J Crohn’s Colitis. 2017;12(1):1–16.
  • García-Olmo D, García-Arranz M, García LG, et al. Autologous stem cell transplantation for treatment of rectovaginal fistula in perianal Crohn’s disease: a new cell-based therapy. Int J Colorectal Dis. 2003;18(5):451–454.
  • 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. 2005;48(7):1416–1423.
  • Garcia-Olmo D, Herreros D, Pascual I, et al. Expanded adipose-derived stem cells for the treatment of complex perianal fistula. Dis Colon Rectum. 2009;52(1):79–86.
  • Ciccocioppo R, Bernardo ME, Sgarella A, et al. Autologous bone marrow-derived mesenchymal stromal cells in the treatment of fistulising Crohn’s disease. Gut. 2011;60(6):788–798.
  • de la Portilla F, Alba F, García-Olmo D, et al. Expanded allogeneic adipose-derived stem cells (eASCs) for the treatment of complex perianal fistula in Crohn’s disease: results from a multicenter phase I/IIa clinical trial. Int J Colorectal Dis. 2013;28(3):313–323.
  • 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(11):2575–2581.
  • Dietz AB, Dozois EJ, Fletcher JG, et al. Autologous mesenchymal stem cells, applied in a bioabsorbable matrix, for treatment of perianal fistulas in patients with Crohn’s disease. Gastroenterology. 2017;153(1):59–62.e2.
  • 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 Transplant. 2013;22(2):279–285.
  • Park KJ, Ryoo SB, Kim JS, et al. Allogeneic adipose-derived stem cells for the treatment of perianal fistula in Crohn’s disease: a pilot clinical trial. Colorectal Dis. 2016;18(5):468–476.
  • Molendijk I, Bonsing BA, Roelofs H, et al. Allogeneic bone marrow-derived mesenchymal stromal cells promote healing of refractory perianal fistulas in patients with Crohn’s disease. Gastroenterology. 2015;149(4):918–927.e6.
  • Cao Y, Ding Z, Han C, et al. Efficacy of mesenchymal stromal cells for fistula treatment of Crohn’s disease: a systematic review and meta-analysis. Dig Dis Sci. 2017;62(4):851–860.
  • 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(5):595–600.
  • 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 Transl Med. 2015;4(5):532–537.
  • Ciccocioppo R, Gallia A, Sgarella A, et al. Long-term follow-up of Crohn disease fistulas after local injections of bone marrow-derived mesenchymal stem cells. Mayo Clin Proc. 2015;90(6):747–755.
  • Panés J, García-Olmo D, Van Assche G, et al. Expanded allogeneic adipose-derived mesenchymal stem cells (Cx601) for complex perianal fistulas in Crohn’s disease: a phase 3 randomised, double-blind controlled trial. Lancet (London, England). 2016;388(10051):1281–1290.
  • Lalu MM, McIntyre L, Pugliese C, et al. Safety of cell therapy with mesenchymal stromal cells (SafeCell): a systematic review and meta-analysis of clinical trials. PLoS One. 2012;7(10):e47559.
  • Prockop DJ, Brenner M, Fibbe WE, et al. Defining the risks of mesenchymal stromal cell therapy. Cytotherapy. 2010;12(5):576–578.
  • Forbes GM, Sturm MJ, Leong RW, et al. A phase 2 study of allogeneic mesenchymal stromal cells for luminal Crohn’s disease refractory to biologic therapy. Clin Gastroenterol Hepatol. 2014;12(1):64–71.
  • Chen Z, He X, He X, et al. Bone marrow mesenchymal stem cells ameliorate colitis-associated tumorigenesis in mice. Biochem Biophys Res Commun. 2014;450(4):1402–1408.
  • Prakash MD, Miller S, Randall-Demllo S, et al. Mesenchymal stem cell treatment of inflammation-induced cancer. Inflamm Bowel Dis. 2016;11:2694–2703.
  • Huang WH, Chang MC, Tsai KS, et al. Mesenchymal stem cells promote growth and angiogenesis of tumors in mice. Oncogene. 2013;32(37):4343–4354.
  • De Boeck A, Pauwels P, Hensen K, et al. Bone marrow-derived mesenchymal stem cells promote colorectal cancer progression through paracrine neuregulin 1/HER3 signalling. Gut. 2013;62(4):550–560.
  • Mele V, Muraro MG, Calabrese D, et al. Mesenchymal stromal cells induce epithelial-to-mesenchymal transition in human colorectal cancer cells through the expression of surface-bound TGF-β. Int J Cancer. 2014;134(11):2583–2594.
  • Widder M, Lützkendorf J, Caysa H, et al. Multipotent mesenchymal stromal cells promote tumor growth in distinct colorectal cancer cells by a β1-integrin-dependent mechanism. Int J Cancer. 2016;138(4):964–975.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.