Stem cell therapeutics: potential in the treatment of inflammatory bowel disease
1Department of Internal Medicine, Section of Digestive Diseases, Yale University School of Medicine, New Haven, CT, USA;
Stem cell therapies may be valuable in treatment of inflammatory bowel disease (IBD). Here we focus on two very different types of stem cells - hematopoietic stem cells and mesenchymal stem cells. Myeloablation and hematopoietic stem cell transplantation alter host immune response by reconstituting the recipient's blood cell lines with donor cells. Autologous hematopoietic reconstitution may "reboot" mucosal immunity to a normal baseline state, but does not alter any underlying genetic predisposition to IBD. In contrast, allogeneic hematopoietic transplantation reconstitutes all blood lineages from a tissue-matched donor who presumably does not have a genetic predisposition to IBD. Compared with autologous hematopoietic transplantation, allogeneic hematopoietic transplantation carries a much greater risk of complications, including graft-versus-host disease. Mesenchymal stem cells can give rise to cartilage, bone and fat in vitro, but do not reconstitute hematopoiesis after transplantation. Systemically infused mesenchymal stem cells appear to favorably downregulate host immune responses through poorly understood mechanisms. In addition, mesenchymal stem cells may be applied topically to help close fistulas associated with Crohn's disease. For all of these stem cell therapy applications for IBD, only cases and small series have been reported. Larger clinical trials are planned or ongoing.
Stem cell therapies may be valuable in treatment of inflammatory bowel disease (IBD). Here we focus on two very different types of stem cells - hematopoietic stem cells and mesenchymal stem cells. Myeloablation and hematopoietic stem cell transplantation alter host immune response by reconstituting the recipient's blood cell lines with donor cells. Autologous hematopoietic reconstitution may "reboot" mucosal immunity to a normal baseline state, but does not alter any underlying genetic predisposition to IBD. In contrast, allogeneic hematopoietic transplantation reconstitutes all blood lineages from a tissue-matched donor who presumably does not have a genetic predisposition to IBD. Compared with autologous hematopoietic transplantation, allogeneic hematopoietic transplantation carries a much greater risk of complications, including graft-versus-host disease. Mesenchymal stem cells can give rise to cartilage, bone and fat in vitro, but do not reconstitute hematopoiesis after transplantation. Systemically infused mesenchymal stem cells appear to favorably downregulate host immune responses through poorly understood mechanisms. In addition, mesenchymal stem cells may be applied topically to help close fistulas associated with Crohn's disease. For all of these stem cell therapy applications for IBD, only cases and small series have been reported. Larger clinical trials are planned or ongoing.
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