Review article: stem cell therapies for inflammatory bowel disease – efficacy and safety

Abstract

Aliment Pharmacol Ther 2010; 32: 939–952 Summary Background Drugs available for the treatment of inflammatory bowel disease fail to induce and maintain remission in a significant number of patients. Aim To assess the value of stem cell therapies for treatment of inflammatory bowel disease based on published studies. Methods Publications were identified through a MEDLINE search using the Medical Subject Heading terms: inflammatory bowel diseases, or Crohn’s disease, or ulcerative colitis, and stem cell, or stromal cell or transplant. Results Haematopoietic stem cell therapy as a primary treatment for inflammatory bowel disease was originally supported by animal experiments, and by remissions in patients undergoing transplant for haematological disorders. Later, transplantation specifically performed for patients with refractory Crohn’s disease showed long‐lasting clinical remission and healing of inflammatory intestinal lesions. Use of autologous nonmyeloablative regimens and concentration of the procedures in centres with large experience are key in reducing treatment‐related mortality. Initial trials of mesenchymal stem cell therapy with local injection in Crohn’s perianal fistulas had positive results. Conclusions Autologous haematopoietic stem cell transplant changes the natural course of Crohn’s disease, and may be a therapeutic option in patients with refractory disease if surgery is not feasible due to disease location or extension.

Remission of refractory Crohn's disease by high‐dose cyclophosphamide and autologous peripheral blood stem cell transplantation

“…22 Long-lasting endoscopic remission occurred in patient #1, in which CDAI was not applicable (Figure 3a). In total, mucosal healing was achieved in 5/9 patients after a mean period of 9.1 months (range [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19], whereas only mild disease activity (aphthous lesions or minor ulcerations) was observed in three patients endoscopically, while patient #12 is awaiting his first endoscopy after autoPBSCT. As exemplified for patient #2 (Fig.…”

“…7,8 The first clinical evidence for the efficacy of auto-PBSCT was based on observations that patients with CD who underwent autoPBSCT for haematological malignancies achieved stable remission of their intestinal disease [reviewed in Ref. (9)]. Almost 10 years ago, the first proof of principle for autoPBSCT as primary therapy for CD was provided by some pioneering case reports, including our own.…”

“…A similar rate of remission was observed in six patients transplanted in Milan 8,16 and in smaller series and independent case reports [reviewed in Refs. (9,17,18)]. In addition, the randomised multicentre ASTIC trial assessing the efficacy of autoPBSCT versus mobilisation therapy alone followed by autoPBSCT at a later time point is ongoing.…”

Stem cell therapy in inflammatory bowel disease: A promising therapeutic strategy?

“…Current studies focus on autologous HSCT, which is intended to "reset" the immune system of the patient. Once reactive T-lymphocytes and memory cells of the patient are eliminated by chemotherapy (lymphoablation), administration of autologous HSCs generates an immunotolerant system [21][22][23] .…”

“…Current studies focus on autologous HSCT, which is intended to "reset" the immune system of the patient. Once reactive T-lymphocytes and memory cells of the patient are eliminated by chemotherapy (lymphoablation), administration of autologous HSCs generates an immunotolerant system [21][22][23] .Unfortunately, this effect will probably be transient until the patient cells start the inflammatory mechanisms again. Clinical experience is limited (Table 1), with the Burt study [25] reporting complete remission in all their 24 patients.…”