Reappraisal of total body irradiation followed by bone marrow transplantation as a therapy for inflammatory bowel disease

A single administration of human adipose tissue-derived mesenchymal stromal cells (MSC) induces durable and sustained long-term regulation of inflammatory response in experimental colitis

“…In general, our results partially corroborate previous studies which showed that the treatment of experimental IBD with bone marrow transplantation associated with immunosuppression leads to the reduction of CD4 + and CD8 + cells in the colon, which seemingly contributes to the improvement of intestinal inflammation and the regression of the disease [16,17]. However, the reduced accumulation of T lymphocytes in the intraepithelial compartment at day 14 after MSC infusion could be indicative of the presence of a potentially inflammatory or pathogenic population in non-treated colitis.…”

“…Recently, transplantation of hematopoietic stem cells (HSCT) has become a therapeutic alternative for autoimmune or inflammatory diseases [14,15]. Preclinical studies have shown that the infusion of bone marrow cells (BMC) has successfully controlled experimental colitis [16,17], with the pretransplant conditioning of immunosuppressive therapies such as cyclophosphamide or total body irradiation. The success of these therapies seem to be more correlated with immunosuppression than with transplantation per se, although prompt bone marrow reconstitution following immune ablation is essential to avoid receptor mortality [16,17].…”

“…To investigate whether the immune modulatory effects assigned to MSC treatment could persist long-term after transplantation, we evaluated the experimental intestinal inflammation induced by a single TNBS infusion during a chronic period of 60 days, as previous studies of the group showed that immunological changes persisted longterm after breakdown of the mucosal tolerance by this hapten [17]. Indeed, even after 60 days of treatment, the potential immune modulatory effects of MSC could still be observed.…”

“…Accordingly, current available treatments are aimed at reducing inflammation in an attempt to avoid disease recurrence or to prolong clinical Clinical and Experimental Immunology ORIgInal aRTIClE remission periods. Preclinical studies have shown that the infusion of bone marrow cells (BMC) has successfully controlled experimental colitis [16,17], with the pretransplant conditioning of immunosuppressive therapies such as cyclophosphamide or total body irradiation. The partial inefficacy of pharmacological interventions and the unresponsiveness of some subjects has spurred clinical interest in developing other approaches for effectively controlling IBD.…”

“…However, many patients are refractory, so that surgery remains their only alternative [13]. The success of these therapies seem to be more correlated with immunosuppression than with transplantation per se, although prompt bone marrow reconstitution following immune ablation is essential to avoid receptor mortality [16,17]. Recently, transplantation of hematopoietic stem cells (HSCT) has become a therapeutic alternative for autoimmune or inflammatory diseases [14,15].…”