Cellular therapy is a promising new approach to address unmet medical needs in patients with IBD, mainly Crohn’s disease (CD). Two series have reported autologous hematopoietic stem cell transplantation (HSCT) for CD. The largest one is a phase I study from Chicago including 24 patients with active CD refractory to conventional therapies. All patients went into remission with a CD Activity Index (CDAI) <150. The percentage of clinical relapse-free survival was 91% at 1 year, 63% at 2 years, 57% at 3 years, 39% at 4 years and 19% at 5 years. The percentage of patients in remission (CDAI <150), steroid-free or medication-free at any post-transplantation evaluation interval remained ≥70, ≥80 and ≥60%, respectively. In Europe and Canada, a currently ongoing randomized trial hopes to answer the question of whether autologous HSCT adds any benefit to the effect of immunosuppression used during mobilization. Although promising, HSCT for CD is still experimental and its toxicity leaves this option for a considerably reduced number of refractory patients in whom the disease is not amenable to surgical resection. A more recently developed, less aggressive approach involves the use of mesenchymal stem cells (MSCs). Successful pre-clinical studies using MSCs in models of autoimmunity, inflammation or tissue damage have paved the way for clinical trials. Two phase I studies on autologous bone marrow-derived MSCs for the treatment of active refractory CD have been published recently; one using systemic administration in patients with luminal CD and the other assessing the effects of local injection of MSCs for the treatment of fistulizing CD, showing that application of autologous MSCs is feasible, well tolerated and might produce clinical benefits.

1.
Peyrin-Biroulet L, Loftus EV Jr, Colombel JF, Sandborn WJ: The natural history of adult Crohn’s disease in population-based cohorts. Am J Gastroenterol 2010;105:289–297.
2.
Chamberlain G, Fox J, Ashton B, Middleton J: Concise review: mesenchymal stem cells: their phenotype, differentiation capacity, immunological features, and potential for homing. Stem Cells 2007;25:2739–2749.
3.
Burt RK, Marmont A, Oyama Y, Slavin S, Arnold R, Hiepe F, et al: Randomized controlled trials of autologous hematopoietic stem cell transplantation for autoimmune diseases: the evolution from myeloablative to lymphoablative transplant regimens. Arthritis Rheum 2006;54:3750–3760.
4.
Gratwohl A, Passweg J, Bocelli-Tyndall C, Fassas A, van Laar JM, Farge D, et al: Autologous hematopoietic stem cell transplantation for autoimmune diseases. Bone Marrow Transplant 2005;35:869–879.
5.
Nash RA, McSweeney PA, Crofford LJ, Abidi M, Chen CS, Godwin JD, et al: High-dose immunosuppressive therapy and autologous hematopoietic cell transplantation for severe systemic sclerosis: long-term follow-up of the US multicenter pilot study. Blood 2007;110:1388–1396.
6.
Burt RK, Traynor A, Statkute L, Barr WG, Rosa R, Schroeder J, et al: Nonmyeloablative hematopoietic stem cell transplantation for systemic lupus erythematosus. JAMA 2006;295:527–535.
7.
Oyama Y, Craig RM, Traynor AE, Quigley K, Statkute L, Halverson A, et al: Autologous hematopoietic stem cell transplantation in patients with refractory Crohn’s disease. Gastroenterology 2005;128:552–563.
8.
Burt RK, Craig RM, Milanetti F, Quigley K, Gozdziak P, Bucha J, et al: Autologous nonmyeloablative hematopoietic stem cell transplantation in patients with severe anti-TNF refractory Crohn disease: long-term follow-up. Blood 2010;116:6123–6132.
9.
Cassinotti A, Annaloro C, Ardizzone S, Onida F, Della Volpe A, Clerici M, et al: Autologous haematopoietic stem cell transplantation without CD34+ cell selection in refractory Crohn’s disease. Gut 2008;57:211–217.
10.
Scime R, Cavallaro AM, Tringali S, Santoro A, Rizzo A, Montalbano L, et al: Complete clinical remission after high-dose immune suppression and autologous hematopoietic stem cell transplantation in severe Crohn’s disease refractory to immunosuppressive and immunomodulator therapy. Inflamm Bowel Dis 2004;10:892–894.
11.
Kreisel W, Potthoff K, Bertz H, Schmitt-Graeff A, Ruf G, Rasenack J, et al: Complete remission of Crohn’s disease after high-dose cyclophosphamide and autologous stem cell transplantation. Bone Marrow Transplant 2003;32:337–340.
12.
Glocker EO, Kotlarz D, Boztug K, Gertz EM, Schäffer AA, Noyan F, et al: Inflammatory bowel disease and mutations affecting the interleukin-10 receptor, N Engl J Med 2009;361:2033–2045.
13.
Aggarwal S, Pittenger MF: Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood 2005;105:1815–1822.
14.
Di Nicola M, Carlo-Stella C, Magni M, Milanesi M, Longoni PD, Matteucci P, et al: Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Blood 2002;99:3838–3843.
15.
Krampera M, Glennie S, Dyson J, Scott D, Laylor R, Simpson E, et al: Bone marrow mesenchymal stem cells inhibit the response of naive and memory antigen-specific T cells to their cognate peptide. Blood 2003;101:3722–3729.
16.
Young HE, Steele TA, Bray RA, Hudson J, Floyd JA, Hawkins K, et al: Human reserve pluripotent mesenchymal stem cells are present in the connective tissues of selecta muscle and dermis derived from fetal, adult and geriatric donors. Anat Rec 2001;264:51–62.
17.
Campagnoli C, Roberts IA, Kumar S, Bennett PR, Bellantuono I, Fisk NM: Identification of mesenchymal stem/progenitor cells in human first-trimester fetal blood, liver, and bone marrow. Blood 2001;98:2396–2402.
18.
Bruder SP, Jaiswal N, Haynesworth SE: Growth kinetics, self-renewal, and the osteogenic potential of purified human mesenchymal stem cells during extensive subcultivation and following cryopreservation. J Cell Biochem 1997;64:278–294.
19.
Le Blanc K, Frassoni F, Ball L, Locatelli F, Roelofs H, Lewis I, et al: Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: a phase II study. Lancet 2008;371:1579–1586.
20.
Duijvestein M, Vos ACW, Roelofs H, Wildenberg ME, Wendrich BB, Verspaget HW, et al: Autologous bone marrow-derived mesenchymal stromal cell treatment for refractory luminal Crohn’s disease: results of a phase I study. Gut 2010;59:1662–1669.
21.
Ciccocioppo R, Bernardo ME, Sgarella A, Maccario R, Avanzini MA, Ubezio C, et al: Autologous bone marrow-derived mesenchymal stromal cells in the treatment of fistulizing Crohn’s disease patients. Gut 2011;60:788–798.
22.
Okamoto R, Matsumoto T, Watanabe M: Regeneration of the intestinal epithelia: regulation of bone marrow-derived epithelial cell differentiation towards secretory lineage cells. Human Cell 2006;19:71–75.
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