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Kazutomo Inoue - One of the best experts on this subject based on the ideXlab platform.

  • hyperglycemia and diabetic renal change in a model of polyvinyl alcohol Bioartificial Pancreas transplantation
    Pancreas, 2007
    Co-Authors: Naoaki Sakata, Shoichiro Sumi, Makoto Sunamura, Seiki Matsuno, Chiduru Yamamoto, Shinichi Egawa, Michiaki Unno, Kazutomo Inoue
    Abstract:

    Objectives We have developed a Bioartificial Pancreas transplantation method using polyvinyl alcohol. Using this model, the relationship between hyperglycemia and parameters that represent renal function was investigated. Methods Plasma glucose, 1,5-anhydro-d-glucitol (1,5-AG), and renal factors including plasma urea nitrogen and creatinine levels, urine volume, glucose, and albumin were examined once a week for 9 weeks in diabetic mice with or without transplantation of encapsulated rat islets, and in normal C57BL/6 mice. The mesangial matrix fraction of the glomerulus was measured histologically. The mice were classified into 3 groups according to their mean plasma glucose levels as either severe (n = 17) or mild (n = 23) hyperglycemia or normoglycemia (n = 11). The plasma glucose, renal factors, and mesangial matrix fraction were tested by single and multiple regression analyses. Results Almost all the renal factors correlated significantly with mean plasma glucose and 1,5-AG levels. The level and duration of hyperglycemia estimated by the area under the curve above basal correlated most significantly with mesangial matrix fraction. Conclusions Bioartificial Pancreas transplantation significantly reduced the deterioration of renal factors. The 1,5-AG was useful to predict urine albumin loss. The level and duration of hyperglycemia determined the degree of renal damage, which were reduced by Bioartificial Pancreas transplantation.

  • effect of rat to mouse Bioartificial Pancreas xenotransplantation on diabetic renal damage and survival
    Pancreas, 2006
    Co-Authors: Naoaki Sakata, Shoichiro Sumi, Chidzuru Yamamoto, Akihito Hiura, Makoto Sunamura, Seiki Matsuno, Kazutomo Inoue
    Abstract:

    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.

  • pva hydrogel sheet macroencapsulation for the Bioartificial Pancreas
    Biomaterials, 2004
    Co-Authors: Naoaki Sakata, Shoichiro Sumi, Akihito Hiura, Dohoon Kim, Yasumasa Shirouzu, Chizuru Yamamoto, Kazutomo Inoue
    Abstract:

    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.

  • the efficient prevascularization induced by fibroblast growth factor 2 with a collagen coated device improves the cell survival of a Bioartificial Pancreas
    Pancreas, 2004
    Co-Authors: Tomonori Sakurai, Shoichiro Sumi, Kazutomo Inoue, Akira Satake, Natsuki Nagata, Yasuhiko Tabata, Junji Miyakoshi
    Abstract:

    OBJECTIVES The subcutaneous transplantation of a Bioartificial Pancreas is a very attractive cure for diabetes mellitus. We recently developed a new immunoisolatory device that has the ability to induce neovascularization for subcutaneous transplantation. We applied the newly developed device to subcutaneous transplantation of a Bioartificial Pancreas. METHODS We investigated the prevascularization-inducing activity of the device in diabetic rats by histologic analysis and evaluated the permeability of the device to insulin and BSA. We also evaluated the survival of cells enclosed in a Bioartificial Pancreas, which was composed of the device, from the viewpoint of the effects of prevascularization by semiquantitative RT-PCR. RESULTS The devices induced prevascularization more efficiently than fibroblast growth factor 2 impregnated in gelatin microspheres alone did and had more useful permeability than a noncollagen-coated device. Significantly higher expression of insulin mRNA was detected in the RT-PCR amplicons from cells retrieved from the Bioartificial Pancreas transplanted at the prevascularization-induced site as compared with at a nonprevascularization-induced site. CONCLUSION We demonstrated that our newly developed device has a superior ability to induce prevascularization in diabetic rats, and the prevascularization improves the initial cell survival of the implanted cells following transplantation.

  • Bioartificial Pancreas transplantation at prevascularized intermuscular space effect of angiogenesis induction on islet survival
    Pancreas, 2003
    Co-Authors: A N Balamurugan, Akira Satake, Natsuki Nagata, Yasuhiko Tabata, Wenjing Wang, Masaaki Miyamoto, Hiroshi Hori, Wanxing Cui, Kazutomo Inoue
    Abstract:

    IntroductionBioartificial Pancreas (BAP) transplantation offers a potential treatment of diabetes mellitus. The optimal site for BAP transplantation has not yet been established.AimTo monitor the effect of induction of neovascularization at the intermuscular space on islet survival after allogenic t

Athanassios Sambanis - One of the best experts on this subject based on the ideXlab platform.

  • therapeutic effects of a non β cell Bioartificial Pancreas in diabetic mice
    Transplantation, 2014
    Co-Authors: Aubrey R Tiernan, Peter M Thule, Athanassios Sambanis
    Abstract:

    Background Cell-based insulin therapies can potentially improve glycemic regulation in insulin-dependent diabetic patients. Enteroendocrine cells engineered to secrete recombinant insulin have exhibited glycemic efficacy, but have been primarily studied as uncontrollable growth systems in immune incompetent mice. Furthermore, reports suggest that suboptimal insulin secretion remains a barrier to expanded application. Methods Genetic and tissue engineering strategies were applied to improve recombinant insulin secretion from intestinal L-cells on both a per-cell and per-graft basis. Transduction of insulin-expressing GLUTag L-cells with lentivirus carrying an additional human insulin gene-enhanced secretion twofold. We infected cells with lentivirus expressing a luciferase reporter gene to track cell survival in vivo. To provide a growth-controlled and immune protective environment without affecting secretory capacity, cells were microencapsulated in barium alginate. Approximately 9×10(7) microencapsulated cells were injected intraperitoneally in immune competent streptozotocin-induced diabetic mice for therapeutic efficacy evaluation. Results Graft insulin secretion was increased to 16 to 24 mU insulin per day. Transient normoglycemia was achieved in treated mice two days after transplantation, and endogenous insulin was sufficient to sustain body weights of treated mice receiving minimal supplementation. Conclusion Glycemic efficacy of a Bioartificial Pancreas based on insulin-secreting enteroendocrine cells is insufficient as a standalone therapy, despite enhancement of graft insulin secretion capacity. Supplemental strategies to alleviate secretion limitations should be pursued.

  • non invasive monitoring of a Bioartificial Pancreas in vitro and in vivo
    Annals of the New York Academy of Sciences, 2006
    Co-Authors: Ioannis Constantinidis, J Robert R Long, Colin Weber, Susan A Safley, Athanassios Sambanis
    Abstract:

    Monitoring biochemical processes relevant to the function, survival, and longevity of tissue-engineered pancreatic constructs is important for the development of an optimum construct design as well as patient care management after implantation. In this report we demonstrate the ability of nuclear magnetic resonance (NMR) techniques to monitor aspects of intracellular metabolism, overall morphology, and distribution of a microencapsulation based Bioartificial Pancreas in vitro and in vivo.

  • development of a Bioartificial Pancreas i long term propagation and basal and induced secretion from entrapped βtc3 cell cultures
    Biotechnology and Bioengineering, 1999
    Co-Authors: Klearchos K Papas, Athanassios Sambanis, Robert C Long, Ioannis Constantinidis
    Abstract:

    Bioartificial pancreatic constructs based on immunoisolated, insulin-secreting cells have the potential for providing effective, long-term treatment of type I (insulin-dependent) diabetes. Use of insulinoma cells, which can be amplified in culture, relaxes the tissue availability limitation that exists with normal pancreatic islet transplantations. We have adopted mouse insulinoma βTC3 cells entrapped in calcium alginate/poly-L-lysine/alginate (APA) beads as our model system for a Bioartificial Pancreas, and we have characterized the effects of long-term propagation and of glucose concentration step changes on the bioenergetic status and on the metabolic and secretory activities of the entrapped cells. Cell bioenergetics were evaluated nonivasively by phosphorus-31 nuclear magnetic resonance (31P NMR) spectroscopy, and metabolic and secretory parameters by assaying cell culture medium. Data indicate that net cell growth occurred between days 3 and 10 of the experiment, resulting in an approximate doubling of the overall metabolic and secretory rates and of the intracellular metabolite levels. Concurrently, a reorganization of cell distribution within the beads was observed. Following this growth period, the measured metabolic and secretory parameters remained constant with time. During glucose step changes in the perfusion medium from a high concentration of 12 to 15 mM to 0 mM for 4.5 h to the same high glucose concentration, the oxygen consumption rate was not affected, whereas insulin secretion was always glucose-responsive. Intracellular nucleotide triphosphates did not change during 0 mM glucose episodes performed early in culture history, but they declined by 20% during episodes performed later in the experiment. It is concluded that the system of APA-entrapped βTC3 cells exhibits several of the desirable characteristics of a Bioartificial Pancreas device, and that a correlation between ATP and the rate of insulin secretion from βTC3 cells exists for only a domain of culture conditions. These findings have significant implications in tissue engineering a long-term functional Bioartificial endocrine Pancreas, in developing noninvasive methods for assessing construct function postimplantation, and in the biochemical processes associated with insulin secretion. © 1999 John Wiley & Sons, Inc. Biotechnol Bioeng 66: 219–230, 1999.

  • development of a Bioartificial Pancreas ii effects of oxygen on long term entrapped βtc3 cell cultures
    Biotechnology and Bioengineering, 1999
    Co-Authors: Klearchos K Papas, Athanassios Sambanis, Robert C Long, Ioannis Constantinidis
    Abstract:

    Tissue-engineered pancreatic constructs based on immunoisolated, insulin-secreting cells are promising in providing an effective, relatively inexpensive, long-term treatment for type I (insulin-dependent) diabetes. An in vitro characterization of construct function under conditions mimicking the in vivo environment is essential prior to any extensive animal experimentation. Encapsulated cells may experience hypoxic conditions postimplantation as a result of one or more of the following: the design of the construct; the environment at the implantation site; or the development of fibrosis around the construct. In this work, we studied the effects of 3- and 4-day-long hypoxic episodes on the metabolic and secretory activities and on the levels of intracellular metabolites detectable by phosphorus-31 nuclear magnetic resonance ((31)P NMR) of alginate/poly-L-lysine/alginate entrapped betaTC3 mouse insulinomas continuously perfused with culture medium. Results show that, upon decreasing the oxygen concentration in the surrounding medium, the encapsulated cell system reached a new, lower metabolic and secretory state. Hypoxia drove the cells to a more anaerobic glycolytic metabolism, increased the rates of glucose consumption (GCR) and lactate production (LPR), and reduced the rates of oxygen consumption (OCR) and insulin secretion (ISR). Furthermore, hypoxia reduced the levels of intracellular nucleotide triphosphates (NTP) and phosphorylcholine (PC) and caused a rapid transient increase in inorganic phosphate (P(i)). Upon restoration of the oxygen concentration in the perfusion medium, all parameters returned to their prehypoxic levels within 2 to 3 days following either gradual unidirectional changes (ISR, NTP, PC) or more complicated dynamic patterns (OCR, GCR, LPR). A further increase in oxygen concentration in the perfusion medium drove OCR, ISR, NTP, PC, and P(i) to new, higher levels. It is concluded that (31)P NMR spectroscopy can be used for the prolonged noninvasive monitoring of the bioenergetic changes of encapsulated betaTC3 cells occurring with changes in oxygen tension. The data also indicate that the oxygen-dependent states might be related to the total number of viable, metabolically active cells supported by the particular oxygen level to which the system is exposed. These findings have significant implications in developing and non-invasively monitoring a tissue-engineered Bioartificial Pancreas based on transformed beta cells, as well as in understanding the biochemical events pertaining to insulin secretion from betaTC3 insulinomas.

  • tissue engineering of a Bioartificial Pancreas modeling the cell environment and device function
    Biotechnology Progress, 1995
    Co-Authors: Evangelos Tziampazis, Athanassios Sambanis
    Abstract:

    Cell-based implantable artificial tissues are most promising for the long-term treatment of endocrine diseases, such as diabetes. One type of a Bioartificial Pancreas device consists of calcium alginate microbeads containing insulin-secreting cells and is surrounded by a poly(L-lysine) (PLL) membrane. The membrane is semipermeable, allowing cellular nutrients and metabolites to diffuse through but excluding the antibodies and cytotoxic cells of the host, thus immunoprotecting the cells. The device can be modeled by writing the equations for diffusion of nutrients and metabolites through the polymer and for consumption of the former and production of the latter by the cells. In this paper, we describe the construction and analysis of such a model for alginate/PLL microbeads with insulin-secreting recombinant mouse pituitary AtT-20 and mouse insulinoma beta TC3 cells. Entrapped AtT-20 cells are a simplified model system, whereas microbeads with beta TC3 cells constitute a realistic artificial pancreatic device. Effective diffusivities of key compounds through the polymer with entrapped, inactivated AtT-20 spheroids were measured first. The kinetics of glucose and oxygen consumption and insulin secretion were modeled next, and the equations for diffusion and reaction were then combined to describe the entire system. The model was used to compute nutrient and metabolite concentration profiles in beads and the bead secretory response for different bead sizes and cell loadings. The size and loading necessary for the cells to be well nourished and for the beads to be rapidly responsive to step-ups and step-downs of secretion stimuli were evaluated. It was shown that if the cells are hypersensitive to glucose, i.e., they do not shut off secretion at the physiological glucose threshold but at a lower one, so are the microbeads. This work demonstrates the usefulness of mechanistic models with representative parameter values in optimizing the design of artificial tissues and in characterizing aspects of their behavior that are of importance for restoring in vivo function.

Shoichiro Sumi - One of the best experts on this subject based on the ideXlab platform.

  • development of polyvinyl alcohol Bioartificial Pancreas with rat islets and mesenchymal stem cells
    Transplantation Proceedings, 2013
    Co-Authors: Gumpei Yoshimatsu, Shoichiro Sumi, Naoaki Sakata, Shinichi Egawa, Haruyuki Tsuchiya, Masaharu Ishida, Fuyuhiko Motoi, Masafumi Goto, Michiaki Unno
    Abstract:

    To improve the function of the polyvinyl alcohol (PVA) Bioartificial Pancreas, we focused on bone marrow-derived mesenchymal stem cells (MSCs). We examined whether the function of PVA-encapsulated rat islets could be improved by coencapsulation with syngeneic MSCs. We macroencapsulated 1,500 rat islet equivalents (IEQ) with or without 1 × 10(6) MSCs with the use of 3% PVA solution before implantation intraperitoneally into diabetic BALB/c mice. We evaluated the function of the device in vitro (the residual rate, viability, and insulin-releasing function of the islets) and in vivo assessments (blood glucose and serum C-peptide changes after transplantation and glucose tolerance test). Although cultured islets also were destroyed, the shapes of the islets cocultured with MSCs were preserved but not different from encapsulated islets without MSCs. At 96 hours after culture the residual rates of islet recovery among those cocultured with versus without MSCs were 66% versus 39.5%, respectively, (P = .03). On the other hand, there was no significant difference between encapsulated islets with versus without MSCs. Furthermore, the stimulation index of the islets was improved by coculture with MSCs (2.6 ± 0.6 vs 1.4 ± 0.1; P = .03), but no beneficial effects were observed between islets encapsulated with versus without MSCs. The viability of islets cocultured with MSCs was significantly better than that without MSCs (84.2 ± 2.5 vs 73.3 ± 0.9; P = .037), but MSCs did not improve the viability of encapsulated islets. There were no significant differences in blood glucose or serum C-peptide between islets encapsulated with versus without MSCs. The histologic findings showed many degenerative islets and MSCs soon after transplantation. In conclusion, further studies are necessary to develop a novel PVA Bioartificial Pancreas that can be used with MSCs.

  • Regenerative medicine for insulin deficiency: creation of pancreatic islets and Bioartificial Pancreas
    Journal of Hepato-Biliary-Pancreatic Sciences, 2011
    Co-Authors: Shoichiro Sumi
    Abstract:

    Recent advances in Pancreas organogenesis have greatly improved the understanding of cell lineage from inner cell mass to fully differentiated β-cells. Based upon such knowledge, insulin-producing cells similar to β-cells to a certain extent have been generated from various cell sources including embryonic stem cells (ESCs) and induced pluripotent stem (iPS) cells, although fully differentiated cells comparable to β-cells are not yet available. The Bioartificial Pancreas is a therapeutic approach to enable allo- and xenotransplantation of islets without immune suppression. Among several types of Bioartificial Pancreases (BAPs), micro-encapsulated porcine islets are already in use in clinical trials and may, perhaps, replace islet transplantation in the near future. Some types of Bioartificial Pancreas such as macro-encapsulation are also useful for keeping transplanted cells enclosed in case retrieval is necessary. Therefore, early clinical applications of artificially generated β-like cells, especially those from ESCs or iPS cells, will be considered in combination with retrievable BAPs.

  • intramedullary cavity as an implant site for Bioartificial Pancreas an in vivo study on diabetic canine
    Transplantation, 2010
    Co-Authors: Kai Chiang Yang, Shoichiro Sumi, Tzongfu Kuo, Sheng Chuan Lin, Fenghuei Lin
    Abstract:

    Background Fibrous tissue outgrowth and hypoxia are the major restrictions for the application of Bioartificial Pancreas (BAP). Accordingly, the intramedullary cavity is proposed as an implant site, and a BAP constructed of calcium phosphate cement chamber was implanted. Methods Mouse insulinoma cells were encapsulated in agarose gel and then enclosed in a calcium phosphate cement chamber to fabricate a BAP. BAPs were implanted in the femoral intramedullary cavity of diabetic dogs. Pre- and postprandial blood glucose levels were monitored perioperatively. Blood samples were collected for the analysis of C-peptide level, and physiological conditions were observed at predetermined intervals. BAPs were retrieved at 12 weeks postoperatively for histologic examination. Results Preprandial blood glucose level of diabetic dogs decreased from 420 ± 25 to 223 ± 47 mg/dL at 1 day postoperatively and was maintained in the range of 259 ± 36 mg/dL for 12 weeks. As serum C-peptide level increased from 5.3 ± 2.8 to 105.7 ± 19.4 pmol/L, the rate of decrease of postprandial blood glucose was accelerated. Histologic examination revealed that recipient bone tissues were binding to the surfaces of BAPs directly; there was no development of fibrous tissue. Immunohistochemical stain was positive for insulin in the enclosed insulinoma cells. Conclusions This study demonstrated that BAPs implanted into the intramedullary cavity functioned well during the experimental period. Thus, the intramedullary cavity can serve as an implant site for BAPs.

  • calcium phosphate cement chamber as an immunoisolative device for Bioartificial Pancreas in vitro and preliminary in vivo study
    Pancreas, 2010
    Co-Authors: Kai Chiang Yang, Shoichiro Sumi, Ching Li Tseng, Tzongfu Kuo, Fenghuei Lin
    Abstract:

    OBJECTIVES This study examined a calcium phosphate cement (CPC) chamber as an immunoisolative device to facilitate the use of xenogeneic cell sources without immunosuppression for the Bioartificial Pancreas (BAP). METHODS Mouse insulinoma cells were encapsulated in agarose gel and then enclosed in a CPC chamber to create a BAP. Bioartificial Pancreas were evaluated by cell viability, live-dead cell ratio, and cytokine-mediated cytotoxicity assay and implanted into the peritoneal cavity of diabetic rats. Nonfasting blood glucose and serum insulin levels were analyzed perioperatively; BAPs were also retrieved for histological examination. RESULTS Insulinoma cells enclosed in the CPC chamber had normal viability, cell survival, and insulin secretion that was even cultured in media with cytokines. The nonfasting blood glucose level of rats was decreased from 460 +/- 50 to 132 +/- 43 mg/dL and maintained euglycemia for 22 days; serum insulin level was increased from 0.34 +/- 0.11 to 1.43 +/- 0.30 microg/dL after operation. Histological examination revealed the fibrous tissue envelopment, and immune-related cells that competed for oxygen resulting in hypoxia could be attributed to the dysfunction of BAPs. CONCLUSIONS This study proved the feasibility for using a CPC chamber as an immunoisolative device for the BAP. An alternative implanted site should be considered to extend the functional longevity of BAPs in further study.

  • comparison of Bioartificial Pancreas performance in the bone marrow cavity and intramuscular space
    Archives of Medical Research, 2010
    Co-Authors: Shoichiro Sumi, Kai Chiang Yang, Jung Chih Chen, Fenghuei Lin
    Abstract:

    Background and Aims Bone marrow with a widely distributed and well-vascularized microenvironment that is capable of sustaining grafts is a potential site for islet transplantation. The femur bone marrow cavity offers sufficient space that may also receive the implantation of Bioartificial Pancreas (BAP). Methods Mouse insulinoma cells encapsulating in agarose gel were further enclosed in a calcium phosphate cement chamber to create a BAP. BAPs implanted into the femur bone marrow cavity of diabetics were compared with those implanted in the intramuscular space. Blood glucose level and C-peptide were determined perioperatively. Results The blood glucose level of the diabetics receiving BAPs in the intramuscular space decreased from 413 ± 24 to 285 ± 47 mg/dL at 1 day post-surgery. However, the blood glucose level returned to 398 ± 35 mg/dL with undetectable serum C-peptide at 2 weeks postoperatively that reveals implant failure. The blood glucose level of diabetics receiving BAPs into the femur bone marrow cavity decreased from 422 ± 32 to 247 ± 52 mg/dL and maintained in the range of 288 ± 47 mg/dL during the experimental period with an increase in C-peptide level from 6.1 ± 2.8 to 104.7 ± 16.4 pmol/L. Conclusions This preliminary study indicates that the effectiveness of BAPs transplanted into the femur bone marrow cavity is superior to that implanted in the intramuscular space, which reveals the bone marrow may be a potential receptor site for the BAP transplantation.

Takashi Maki - One of the best experts on this subject based on the ideXlab platform.

  • Porcine islet xenotransplantation utilizing a vascularized Bioartificial Pancreas.
    Annals of transplantation, 1997
    Co-Authors: Takashi Maki, Anthony P. Monaco
    Abstract:

    Successful Pancreas/islet transplantation restores normal glucose metabolism in patients with insulin dependent diabetes mellitus (IDDM) but requires chronic immunosuppression which is associated with morbidity and mortality. Immune exclusion devices containing pancreatic islets (Bioartificial Pancreas) are designed to provide glycemic control without immunosuppression. The immune exclusion is achieved by separating islets from the host by semipermeable membranes. Small molecules such as glucose, insulin and nutrients pass through, whereas immune lymphocytes and immunoglobulins are excluded by the membrane and unable to cause destruction of the islets. Use of xenogeneic islets (i.e., porcine islets) in the device also circumvents the shortage of human donor organs. This report provides a brief summary of our experience with vascularized Bioartificial Pancreas (VBAP) containing allogeneic and xenogeneic islets for treatment of experimental diabetes in dogs and describes our plans for a clinical trial of the VBAP in patients with IDDM.

  • islet transplantation in the future use of a Bioartificial Pancreas
    Journal of Hepato-biliary-pancreatic Surgery, 1996
    Co-Authors: Takashi Maki
    Abstract:

    Tight glycemic control effectively delays the onset and slows the progression of diabetic complications in patients with insulin-dependent diabetes mellitus. Successful Pancreas transplantation corrects abnormal glucose metabolism but subjects patients to morbidity and mortality associated with chronic immunosuppression. Immune exclusion devices containing pancreatic islets (Bioartificial Pancreas devices) are designed to provide glycemic control through islet transplantation without immunosuppression. The immune exclussion is achieved by separating allogeneic or xenogeneic islets from the host by semipermeable membranes that allow only small molecules, such as glucose, insulin, and nutrients, to pass through. Immune lymphocytes and immunoglobulins are excluded by the membrane and are unable to cause destruction of the islets. This report provides a brief review of three types of Bioartificial Pancreas devices used for the treatment of diabetes, i.e., perfusion-based vascular devices, diffusion-based chambers and microcapsules, and describes recent progress in each area.

  • treatment of diabetes by xenogeneic islets without immunosuppression use of a vascularized Bioartificial Pancreas
    Diabetes, 1996
    Co-Authors: Takashi Maki, Claudy J.-p. Mullon, Barry A. Solomon, Ichiro Otsu, John J Oneil, Karen E Dunleavy, Anthony P. Monaco
    Abstract:

    Tight glycemic control by intensive insulin therapy effectively delays the onset and slows the progression of diabetic complications but is associated with frequent dose adjustments and a high incidence of hypoglycemia. Successful Pancreas transplantation corrects abnormal glucose metabolism but subjects patients to morbidity and mortality associated with chronic immunosuppression. A vascularized artificial Pancreas device containing pancreatic islets is designed to provide glycemic control without immunosuppression. We report here that devices seeded with porcine islets implanted into pancreatectomized severely diabetic dogs maintained a marked improvement in glycemic control with reduced exogenous insulin requirements for up to 9 months with improved glucose tolerance and a reduction in glycosylated hemoglobin levels. No immunosuppression was used. Thus, use of a vascularized artificial Pancreas containing xenogeneic porcine islets could be an alternative to intensive insulin therapy and pancreatic transplantation in treating diabetic patients before the development of severe diabetic complications.

  • Early treatment of diabetes with porcine islets in a Bioartificial Pancreas.
    Tissue engineering, 1996
    Co-Authors: Takashi Maki, Anthony P. Monaco, Claudy J.-p. Mullon, Barry A. Solomon
    Abstract:

    Successful Pancreas transplantation is an effective therapy for insulin-dependent diabetes mellitus (IDDM) but subjects patients to morbidity and mortality associated with chronic immunosuppression. Bioartificial Pancreas devices containing pancreatic islets provide glycemic control without immunosuppression by physically separating the islet grafts from immune lymphocytes and immunoglobulins. Because immunosuppression is not required, the Bioartificial Pancreas may offer early treatment of IDDM prior to the development of debilitating diabetic complications. Use of xenogeneic islets (i.e., porcine islets) in the device also provides a solution to the limited availability of human donor organs. This report provides a brief summary of our experience with vascularized Bioartificial Pancreas devices containing xenogeneic porcine islets used for treatment of experimental diabetes in dogs and describes our plans for a clinical phase I/II trial of the vascularized Bioartificial Pancreas in patients with IDDM.

Yoav Evron - One of the best experts on this subject based on the ideXlab platform.

  • enhanced oxygen supply improves islet viability in a new Bioartificial Pancreas
    Cell Transplantation, 2013
    Co-Authors: Uriel Barkai, Clark K Colton, Gordon C Weir, Barbara Ludwig, Stefan R Bornstein, Mathias D Brendel, Tova Neufeld, Chezi Bremer, Assaf Leon, Yoav Evron
    Abstract:

    The current epidemic of diabetes with its overwhelming burden on our healthcare system requires better therapeutic strategies. Here we present a promising novel approach for a curative strategy that may be accessible for all insulin-dependent diabetes patients. We designed a subcutaneous implantable Bioartificial Pancreas (BAP)-the "beta-Air" that is able to overcome critical challenges in current clinical islet transplantation protocols: adequate oxygen supply to the graft and protection of donor islets against the host immune system. The system consists of islets of Langerhans immobilized in an alginate hydrogel, a gas chamber, a gas permeable membrane, an external membrane, and a mechanical support. The minimally invasive implantable device, refueled with oxygen via subdermally implanted access ports, completely normalized diabetic indicators of glycemic control (blood glucose intravenous glucose tolerance test and HbA1c) in streptozotocin-induced diabetic rats for periods up to 6 months. The functionality of the device was dependent on oxygen supply to the device as the grafts failed when oxygen supply was ceased. In addition, we showed that the device is immuno-protective as it allowed for survival of not only isografts but also of allografts. Histological examination of the explanted devices demonstrated morphologically and functionally intact islets; the surrounding tissue was without signs of inflammation and showed visual evidence of vasculature at the site of implantation. Further increase in islets loading density will justify the translation of the system to clinical trials, opening up the potential for a novel approach in diabetes therapy.

  • enhanced oxygen supply improves islet viability in a new Bioartificial Pancreas
    Cell Transplantation, 2013
    Co-Authors: Uriel Barkai, Clark K Colton, Gordon C Weir, Barbara Ludwig, Stefan R Bornstein, Mathias D Brendel, Tova Neufeld, Chezi Bremer, Assaf Leon, Yoav Evron
    Abstract:

    The current epidemic of diabetes with its overwhelming burden on our healthcare system requires better therapeutic strategies. Here we present a promising novel approach for a curative strategy that may be accessible for all insulin-dependent diabetes patients. We designed a subcutaneous implantable Bioartificial Pancreas (BAP)-the "β-Air"-that is able to overcome critical challenges in current clinical islet transplantation protocols: adequate oxygen supply to the graft and protection of donor islets against the host immune system. The system consists of islets of Langerhans immobilized in an alginate hydrogel, a gas chamber, a gas permeable membrane, an external membrane, and a mechanical support. The minimally invasive implantable device, refueled with oxygen via subdermally implanted access ports, completely normalized diabetic indicators of glycemic control (blood glucose intravenous glucose tolerance test and HbA1c) in streptozotocin-induced diabetic rats for periods up to 6 months. The functionality of the device was dependent on oxygen supply to the device as the grafts failed when oxygen supply was ceased. In addition, we showed that the device is immuno-protective as it allowed for survival of not only isografts but also of allografts. Histological examination of the explanted devices demonstrated morphologically and functionally intact islets; the surrounding tissue was without signs of inflammation and showed visual evidence of vasculature at the site of implantation. Further increase in islets loading density will justify the translation of the system to clinical trials, opening up the potential for a novel approach in diabetes therapy.