A Gelatin Hydrogel Nonwoven Fabric Combined With Adipose Tissue-Derived Stem Cells Enhances Subcutaneous Islet Engraftment.

Subcutaneous islet transplantation is a promising treatment for severe diabetes; however, poor engraftment hinders its prevalence. We previously revealed that a gelatin hydrogel nonwoven fabric (GHNF) markedly improved subcutaneous islet engraftment. We herein investigated whether the addition of adipose tissue-derived stem cells (ADSCs) to GHNF affected the outcome. A silicone spacer sandwiched between two GHNFs with (AG group) or without (GHNF group) ADSCs, or a silicone spacer alone (Silicone group) was implanted into the subcutaneous space of healthy mice at 6 weeks before transplantation, then diabetes was induced 7 days before transplantation. Syngeneic islets were transplanted into the pretreated space. Intraportal transplantation (IPO group) was also performed to compare the transplant efficiency. Blood glucose, intraperitoneal glucose tolerance, immunohistochemistry, and inflammatory mediators were evaluated. The results in the subcutaneous transplantation were compared using the Silicone group as a control. The results of the IPO group were also compared with those of the AG group. The AG group showed significantly better blood glucose changes than the Silicone and the IPO groups. The cure rate of AG group (72.7%) was the highest among the groups (GHNF; 40.0%, IPO; 40.0%, Silicone; 0%). The number of vWF-positive vessels in the subcutaneous space of the AG group was significantly higher than that in other groups before transplantation (P < 0.01). Lectin angiography also showed that the same results (P < 0.05). According to the results of the ADSCs tracing, ADSCs did not exist at the transplant site (6 weeks after implantation). The positive rates for laminin and collagen III constructed around the transplanted islets did not differ among groups. Inflammatory mediators were higher in the Silicone group, followed by the AG and GHNF groups. Pretreatment using bioabsorbable scaffolds combined with ADSCs enhanced neovascularization in subcutaneous space, and subcutaneous islet transplantation using GHNF with ADSCs was superior to intraportal islet transplantation.

A Gelatin Hydrogel Nonwoven Fabric Enhances Subcutaneous Islet Engraftment in Rats.

Although subcutaneous islet transplantation has many advantages, the subcutaneous space is poor in vessels and transplant efficiency is still low in animal models, except in mice. Subcutaneous islet transplantation using a two-step approach has been proposed, in which a favorable cavity is first prepared using various materials, followed by islet transplantation into the preformed cavity. We previously reported the efficacy of pretreatment using gelatin hydrogel nonwoven fabric (GHNF), and the length of the pretreatment period influenced the results in a mouse model. We investigated whether the preimplantation of GHNF could improve the subcutaneous islet transplantation outcomes in a rat model. GHNF sheets sandwiching a silicone spacer (GHNF group) and silicone spacers without GHNF sheets (control group) were implanted into the subcutaneous space of recipients three weeks before islet transplantation, and diabetes was induced seven days before islet transplantation. Syngeneic islets were transplanted into the space where the silicone spacer was removed. Blood glucose levels, glucose tolerance, immunohistochemistry, and neovascularization were evaluated. The GHNF group showed significantly better blood glucose changes than the control group (p < 0.01). The cure rate was significantly higher in the GHNF group (p < 0.05). The number of vWF-positive vessels was significantly higher in the GHNF group (p < 0.01), and lectin angiography showed the same tendency (p < 0.05). The expression of laminin and collagen III around the transplanted islets was also higher in the GHNF group (p < 0.01). GHNF pretreatment was effective in a rat model, and the main mechanisms might be neovascularization and compensation of the extracellular matrices.

Ghrelin stimulates corticotropin-releasing factor and vasopressin gene expression in rat hypothalamic 4B cells.

Corticotropin-releasing factor (CRF) and arginine vasopressin (AVP) play a central role in regulating the stress response. In response to stress, CRF and AVP neurons in the hypothalamic paraventricular nucleus secrete the peptides to stimulate the release of adrenocorticotropic hormone from the anterior pituitary. Ghrelin, an endogenous ligand of the growth hormone-releasing peptide receptors (GHSR), has been shown to stimulate the release of CRF and AVP by rat hypothalamic explants. However, little is known about the ability of the ghrelin signaling pathways to activate the CRF and AVP genes in the hypothalamus. In the present study, we examined the direct effect of ghrelin on CRF and AVP gene expression in hypothalamic 4B cells, which show the characteristics of the hypothalamic parvocellular paraventricular nucleus neurons. Cells were transfected with CRF or AVP promoter to examine the activity of each promoter. Ghrelin stimulated the promoter activities and mRNA levels for both CRF and AVP. The involvement of a protein kinase pathway was examined using inhibitors. Protein kinase A and phospholipase C pathways were shown to be involved in ghrelin-induced increases in both CRF and AVP promoter activities. GHSR type 1a (GHSR1a) mRNA levels were also increased by ghrelin, and these ghrelin-induced levels were suppressed by a GHSR1a antagonist. Thus, ghrelin-dependent pathways are involved in the regulation of CRF and AVP gene expression in the hypothalamus: ghrelin, an orexigenic hormone, stimulates CRF, an anorexigenic/anxiogenic factor in the hypothalamus, resulting in hypothalamic-pituitary-adrenal axis activation to stimulate the release of glucocorticoids.

Usefulness of laparoscopic posterior rectopexy for complete rectal prolapse: A cohort study.

BACKGROUND: Transabdominal rectopexy for complete rectal prolapse reportedly yields more definitive results than transperineal surgery. Recently, minimally invasive laparoscopic rectopexy has become a popular treatment option for patients with rectal prolapse. Herein, we describe our surgical procedure for correction of rectal prolapse. We further aimed to perform a comparative assessment between perioperative outcomes achieved with open and laparoscopic applications of this technique. MATERIALS AND METHODS: In this cohort study, 65 patients underwent posterior rectopexy (laparoscopic, 50; open, 15) between April 2008 and December 2015. The basic procedure consisted of posterior rectopexy using mesh fixation (modified Wells' method). We assessed and compared perioperative outcomes (duration of surgery and hospitalization, complication rates, blood-loss, degree of fecal incontinence) of laparoscopic and open rectopexy. Furthermore, pre- and post-operative urinary incontinence was measured (using pad test, questionnaire) and compared to determine the effects of the procedure on pelvic organ function. A p-value <0.05 indicated statistical significance. RESULTS: The mean operative time of the laparoscopic and open procedures was 127 and 83.6 min, respectively. The amount of blood-loss was negligible and 77 (range, 18-200) g with the laparoscopic and open approaches, respectively. The mean duration of hospitalization was 4.2 and 7.2 days for the former and latter procedures, respectively (p < 0.05). Rectal prolapse and fecal incontinence (evaluated using Wexner's score) diminished in all patients. Urinary incontinence also decreased postoperatively. There were no recurrences of rectal prolapse. CONCLUSION: Laparoscopic rectopexy can be safely performed in older patients to achieve early postoperative ambulation and significantly shorten the hospital-stay. It may therefore be considered an effective treatment for complete rectal prolapse and urinary dysfunction.