Regeneration of the rat neonatal intestine in transplantation.

Recent interest in the use of cells from a fetus or a newborn as a source of somatic stem cells has increased in the area of regeneration medicine. The fetus and newborns possess active regenerative capability, and their immune function is premature compared with adults. For example, postnatal rodent animals have stem cells in their small intestine, which can generate new small intestinal mucosa.1,2 Application of recent cryopreservation techniques might enhance the viability of the newborn intestine. On the other hand, severe impairment of nutrient absorption results in clinical morbidity and mortality in the majority of patients with small intestinal failure such as short bowel syndrome.3–5 Small intestinal transplantation is an optional treatment of patients with intestinal failure in an effort to sustain their life.4 However, given chronic donor shortages, cadavaric intestinal transplantation remains limited, and the clinical results of intestinal transplantation do not always compare well with other organ transplantations. Since the small intestine is a high immunogenic organ, it is difficult to control acute and chronic rejection. Subsequently, issues concerning the immunologic unresponsiveness of recipients still need to be addressed, despite advances in the immunosuppressive regimen. In our previous study, we demonstrated prolonged survival and subsequent development of the cryopreserved newborn intestine when the grafts were transplanted into the subcutaneous space of adult rats without vascular anastomosis between the graft and the recipient.6,7 Thus, newborn intestine possesses promising potential as a donor graft in the field of intestinal transplantation. To ensure the generation of a fully mature intestine from an avascular newborn intestinal graft, neo-angiogenesis is thought to be essential between the graft and the recipient.8 Given that the maturation ability of a fetal intestinal graft gradually decreases with time, angiogenesis should specifically occur shortly after birth.9 Many uncharacterized factors, however, are implicated in the enhanced survival of a newborn intestinal graft, the precise mechanisms of which remain unclear. In this study, we addressed the regenerative potential of newborn intestine with or without cryopreservation in the transplantation. Interestingly, we found that the newborn intestinal graft was capable of promoting the survival of a 10-day-old intestinal graft that lacked regenerating potential when both grafts were adhered to each other in parallel. Furthermore, we comprehensively analyzed the differential gene expression pattern between the competent and the incompetent 10-day-old intestine using a high-throughput microarray technique. These results may provide new insights into the regenerative role of newborn intestinal grafts.