PubMed Health⌕ Search

Biomedical subjects

Akihito Hiura

Publications and source records attributed to Akihito Hiura.

9 recordsLinked to original sources
PubMed2006

Oral administration of nicorandil enhances the survival of ischemic skin flaps in rats.

Nicorandil has an anti-apoptotic effect on ischemic myocardium through the activation of ATP-sensitive potassium (K(ATP)) channel. We tested the hypothesis that oral administration of nicorandil had a protective effect on ischemic skin flaps. A cranially based skin flap measuring 3x7 cm in full thickness was made on the back of rats. The rats were divided into a control group and 8 nicorandil groups (group 1-8) according to different doses and timings of administration. On day 7 at 5 cm, groups 1 to 6 (10 or 30 mg/kg twice per day for 3 days starting at 24 h before, 0.5 h before or 0.5 h after the operation) showed significantly higher blood perfusion change rate (73.3+/-2.9%-79.1+/-4.1% vs. 25.9+/-8.6%, P<0.01), and significantly higher survival rate (68.8+/-4.8-75.2+/-8.2% vs. 47.0+/-2.8%, P<0.05) than the control group. Many more surviving blood vessels were also observed in these groups. In contrast, no significant effects were found either in group 7 (30 mg/kg twice per day for 3 days starting 24 h after the operation) or group 8 (30 mg/kg once at 0.5 h after the operation). We did not find an angiogenic effect of nicorandil in vitro. Therefore, our results confirmed that the oral administration of nicorandil could protect tissues from necrosis in ischemic skin flaps. In addition, its protective effect depends on the time of first administration and the duration.

Animals↗
PubMed2006

Effect of rat-to-mouse bioartificial pancreas xenotransplantation on diabetic renal damage and survival.

OBJECTIVE: Diabetic nephropathy is a life-threatening complication of diabetes mellitus. Bioartificial pancreas transplantation is becoming a therapeutic option for diabetes mellitus as it protects both allogeneic and xenogeneic islets from the host immune system. This study was undertaken to determine the effectiveness of bioartificial pancreas transplantation to improve or prevent diabetic renal damage. METHODS: Approximately 800 rat islets were macroencapsulated in polyvinyl alcohol gel and then transplanted into the peritoneal cavity of diabetic mice (transplantation group [Tx group]). Diabetic mice transplanted with a capsule without islets served as a sham operation group. After transplantation, the following data were collected: survival, body weight, blood glucose, blood urea nitrogen, serum creatinine levels, urinalysis, water intake, and histological changes in the kidney. RESULTS: There was a significant improvement in survival, blood glucose, blood urea nitrogen, and creatinine in the Tx group compared with the sham operation group. No remarkable changes were seen in urinary parameters between the 2 groups, and there was also no significant difference in water intake. Histological examination revealed that mesangial matrix expansion was decreased in the Tx group. CONCLUSIONS: This study demonstrated that polyvinyl alcohol gel bioartificial pancreas transplantation can protect the kidney from diabetic damage.

Animals↗
PubMed2005

Cold preservation of islets in UW solution--with special reference to apoptosis.

BACKGROUND: Apoptosis progresses in cultured islets. Little is known with regard to apoptosis under cold preservation. We examined viability and function of islets in University of Wisconsin (UW) solution. MATERIALS AND METHODS: Isolated rat islets were cultured overnight (overnight group) and further treated with 7-day culture in RPMI 1640 medium at 37 degrees C (culture group) or 7-day preservation in UW solution at 4 degrees C (preservation group). They were evaluated by glucose-stimulated insulin secretion test. Apoptosis was examined by TdT-mediated dUTP-biotin nick end-labeling (TUNEL) assay. Expression of caspase mRNA and the ratio of Bax to Bcl-2 were evaluated by reverse-transcriptase polymerase chain reaction (RT-PCR). RESULTS: Islet recovery after 7 days was significantly lower in culture group than in preservation group (44.0 +/- 3.7% versus 75.0 +/- 4.9%, P < 0.05). The stimulation index in the culture group was significantly lower than in the overnight group (2.1 +/- 0.2 versus 4.1 +/- 0.4, P < 0.05). The apoptotic index in the culture group was significantly higher than both in the overnight group and in the preservation group (38.0 +/- 3.0% versus 10.8 +/- 2.0 and 27.0 +/- 4.0%, P < 0.05). Caspase 3, 8, and 9 mRNA in the culture group expressed more than in the other groups. Bax/Bcl-2 in the culture group was significantly lower than in the overnight group (3.2 +/- 0.66 versus 8.1 +/- 0.95, P < 0.05), suggesting that apoptosis had been already destined early after isolation. CONCLUSIONS: The preservation group showed better recovery and function than the culture group. Apoptosis contributed to islet loss under culture and it was significantly suppressed under cold preservation.

Adenosine↗
PubMed2004

PVA hydrogel sheet macroencapsulation for the bioartificial pancreas.

We newly developed a sheet-type macroencapsulation device entrapping rat islets from 3% polyvinyl alcohol (PVA) dissolved in Euro-Collins solution containing 10% fetal bovine serum and 5% dimethyl sulfoxide (PVA + EC) using a freezing/thawing technique. The same encapsulation technique but with 3% PVA dissolved only in double-distilled water (PVA) and a culture of free islets were served as controls. After 14-day culture in the CMRL-1066 medium, the islet recovery rate, morphological changes, insulin content, and insulin secretion were evaluated in vitro to prove the feasibility of this method of encapsulation. We also xenotransplanted the device into the peritoneal cavity of diabetic C57BL/6 mice to check its function in vivo. After 1-day culture, the islet recovery rate and insulin content in the PVA group were significantly lower than that in the PVA + EC and free islet groups. After 14-day culture, only the islets in the PVA+EC group maintained a normal morphology and effective insulin secretory response to high glucose while the response was not observed in the PVA group after 1-day culture and no longer observed in the free islets after 7-day culture. After transplantation of rat islets encapsulated in the PVA + EC device to diabetic C57BL/6 mice, nonfasting blood glucose levels showed a rapid decrease from high glucose levels of pre-transplantation, maintaining significantly lower glucose levels during the whole course of study in comparison with the sham-operated group. Our results indicated that this freezing/thawing macroencapsulation technique using 3% PVA + EC was effective for xenotransplantation of islet cells.

Animals↗
PubMed2004

Stem cells and regenerative medicine for diabetes mellitus.

A profound knowledge of the development and differentiation of pancreatic tissues, especially islets of Langerhans, is necessary for developing regenerative therapy for severe diabetes mellitus. A recent developmental study showed that PTF-1a is expressed in almost all parts of pancreatic tissues, in addition to PDX-1, a well-known transcription factor that is essential for pancreas development. Another study suggested that alpha cells and beta cells individually, but not sequentially, differentiated from neurogenin-3--expressing precursor cells. Under strong induction of pancreas regeneration, it is likely that pancreatic duct cells dedifferentiate to grow, express PDX-1, and re-differentiate toward other cell types including islet cells. Duct epithelium-like cells can be cultivated from crude pancreatic exocrine cells and can be induced to differentiate toward islet-like cell clusters under some culture conditions. These cell clusters made from murine pancreas have been shown to control hyperglycemia when transplanted into diabetic mice. Liver-derived oval cells and their putative precursor H-CFU-C have been shown to differentiate toward pancreatic cells. Furthermore, extrapancreatic cells contained in bone marrow and amniotic membrane are reported to become insulin-producing cells. However, their exact characterization and relationship between these cell types remain to be elucidated. Our recent study has shown that islet-like cell clusters can be differentiated from mouse embryonic stem cells. Transplantation of these clusters could ameliorate hyperglycemia of STZ-induced diabetic mice without forming teratomas. Interestingly, these cells expressed several genes specific to exocrine pancreatic tissue in addition to islet-related genes, suggesting that stable and efficient differentiation toward certain tissues can only be achieved through a process mimicking normal development of the tissue. Perhaps recent developments in these fields may rapidly lead to an established regenerative therapy for diabetes mellitus.

Animals↗
PubMed2003

Subcutaneous transplantation of macroencapsulated porcine pancreatic endocrine cells normalizes hyperglycemia in diabetic mice.

BACKGROUND: The ultimate goal of islet transplantation is the unlimited availability of insulin-secreting cells to be transplanted in a simple procedure that requires no use of immunosuppressive drugs. Immunoisolation of xenogeneic pig islets for transplantation has great potential therapeutic benefits for treatment of diabetes. METHODS: Approximately 4 x 10(6) porcine pancreatic endocrine cells (PEC) isolated from 6-month-old pigs were macroencapsulated in agarose-poly(styrene sulfonic acid) mixed gel and implanted into a prevascularized subcutaneous site in streptozotocin-induced C57BL/6 diabetic mice. Animals receiving an equal number of free porcine PEC were used as controls. After transplantation, nonfasting blood glucose, body weight, intraperitoneal glucose tolerance test, and immunohistologic evaluations were processed. RESULTS: All 10 animals receiving the subcutaneous xenografts of the macroencapsulated porcine PEC normalized hyperglycemia within 5 days after transplantation, maintained the duration of normoglycemia for 24 to 76 days, and gradually gained weight. The subcutaneous xenografts of free porcine PEC could not reverse hyperglycemia. The recipient became hyperglycemic again when the implanted graft was retrieved at day 45 after transplantation. The glucose clearances were significantly ameliorated at day 21 and day 45 after transplantation when compared with those in diabetic mice. The immunohistochemical results revealed an inherent intact structure of the macroencapsulated porcine PEC and positive double-immunofluorescence staining for insulin and glucagon. CONCLUSIONS: Subcutaneous transplantation of macroencapsulated porcine PEC normalized hyperglycemia in diabetic mice. Our results identified a potential for a favorable development of subcutaneous transplantation of porcine PEC as a cure for diabetes.

Animals↗
PubMed2003

The development of new immunoisolatory devices possessing the ability to induce neovascularization.

The transplantation of a bioartificial pancreas has been regarded as a potential method for successful islet transplantation without any immunosuppressive agents. The subcutaneous site is a very attractive site for transplantation of a bioartificial pancreas because of its advantage of an easy operation site. Our group has been reporting that transplantation of a bioartificial pancreas to the subcutaneous site can reverse hyperglycemia in diabetic recipients. Regarding shapes of a bioartificial pancreas, it is believed that a bag form has an advantage because it is easy to prepare a large quantity. Our group previously reported successful transplantation of a bioartificial pancreas in bag form, a mesh-reinforced polyvinyl alcohol bag (MRPB), implanted in the peritoneal cavity. We also reported that the effect of subcutaneous islet transplantation can be greatly improved with prevascularization treatment. In the present study, we attempted to combine MRPB to our protocol of subcutaneous prevascularization. The main problem of this trial is that the procedure of MRPB implantation injures the prevascularized blood vessel networks. To solve this problem, we made a slight alternation in our protocol, and designed new devices on the basis of MRPB. The new devices, possessing the ability to induce neovascularization, were prepared by collagen coating on the surface of MRPB and were implanted with/without different doses of FGF-2 impregnated in gelatin microspheres. When using 5 microg of FGF-2, more blood vessels were observed on the surface of type I/IV collagen-coated MRPB compared with the original MRPB and type I collagen-coated MRPB. Quite a few blood vessels were observed either around the injection site of 50 microg of FGF-2 impregnated in gelatin microspheres alone or around the implantation site of FGF-2-free gelatin microspheres and type I collagen-coated MRPB or type I/IV collagen-coated MRPB. Here we demonstrated that the combination of both FGF-2 impregnated in gelatin microspheres and collagen-coated MRPB could give an effective system of neovascularization suitable for subcutaneous implantation of a bioartificial pancreas.

Animals↗
PubMed2003

[Introduction: development and prospective of regenerative medicine].

The goal of regenerative medicine is the reconstruction of tissues and organs using various cells, the ideal of which is the ex vivo reconstruction of both form and function. The technique and development are different in each organ. As to details, each subject would be referred. Although basic investigations in Japan compare favorably with those in USA and Europe especially in the field of growth factors, Japan is obviously behind these countries in the research of connecting the basic results to industrialization. Moreover, ethical problems, safety and stability of cells, and obtaining social consensus are essential to be resolved.

Animals↗