池田 太郎

PURPOSE: Our previous studies demonstrated that mature adipocyte-derived dedifferentiated fat (DFAT) cells possess similar multipotency as mesenchymal stem cells. Here, we examined the immunoregulatory potential of DFAT cells in vitro and the therapeutic effect of DFAT cell transplantation in a mouse inflammatory bowel disease (IBD) model. METHODS: The effect of DFAT cell co-culture on T cell proliferation and expression of immunosuppression-related genes in DFAT cells were evaluated. To create IBD, CD4+CD45RBhigh T cells were intraperitoneally injected into SCID mice. One week later, DFAT cells (1 × 105, DFAT group) or saline (Control group) were intraperitoneally injected. Subsequently bodyweight was measured every week and IBD clinical and histological scores were evaluated at 5 weeks after T cell administration. RESULTS: The T cell proliferation was inhibited by co-cultured DFAT cells in a cell density-dependent manner. Gene expression of TRAIL, IDO1, and NOS2 in DFAT cells was upregulated by TNFα stimulation. DFAT group improved IBD-associated weight loss, IBD clinical and histological scores compared to Control group. CONCLUSION: DFAT cells possess immunoregulatory potential and the cell transplantation promoted recovery from colon damage and improved clinical symptoms in the IBD model. DFAT cells could play an important role in the treatment of IBD.

We describe the physiological examination of anorectal function in children with chronic constipation (CC), including Hirschsprung's (H) disease (aganglionosis) and its allied disorders [hypoganglionosis (Hypo) and intestinal neuronal dysplasia (IND)]. The assessments are summarized as follows: 1) Anorectal manometry: Enteric nervous system, especially non-adrenergic non-cholinergic excitatory and inhibitory nerves, controls the ano-rectal sphincter reflex. Therefore, patients with aganglionosis lack ano-rectal sphincter reflexes. Abnormalities of the enteric nervous system in Hypo and IND show atypical sphincter reflexes. In contrast, CC patients exhibit normal sphincter reflexes. 2) Terminal motor latency in the pudendal and sacral nerves: Patients with aganglionosis, Hypo, IND and CC exhibit conduction delay of these nerves. These findings may suggest damage to the pudendal and sacral motor nerves due to straining during defecation. 3) Anal canal sensation test (anal canal mucosal electrosensitivity and somatosensory evoked potential tests): Anal sensation is decreased in patients with H disease, Hypo, IND and CC. These findings may suggest damage to the pudendal sensory nerves due to straining during defecation. 4) Defecography: This examination easily detects an obstructive type in school-age patients with CC. 5) Gastrointestinal transit time: This examination easily detects the slow transit type in school-age patients with CC. Conclusions: It is easy for pediatric surgeons to evaluate physiological function in patients with CC, H disease and its allied diseases using physiological examinations.