Membrane Bioreactors as Hybrid Artificial Pancreas: Experimental Evaluation (original) (raw)
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Biohybrid artificial pancreas. Long-term insulin secretion by devices seeded with canine islets
Diabetes, 1985
Long-term insulin secretion was investigated in seven biohybrid capillary devices seeded with canine islets. Approximately 50,000 islets could be isolated from a single canine pancreas using collagenase digestion in conjunction with the recently described Velcro technique. Devices were perfused with tissue culture medium 199 containing 300 mg/dl glucose. Insulin secretion fell during the first 1-2 days of culture from approximately 18 to 6 U/day. After 3-4 wk of perfusion, however, there was a gradual rise in insulin output that reached >15 U/day after 7 wk. Insulin output eventually stabilized at 18-20 U/day. Two of these devices were studied for 80 and 86 days, respectively, and continued to secrete these same amounts of insulin. Glucose-induced insulin release was studied after 1 and 4 wk of culture and was well preserved. DIABETES 1985; 34:850-54. T he biohybrid artificial pancreas offers a potential solution to several of the major problems involved in transplantation of insulin-producing tissue in diabetic patients. In this device beta cells are separated from the blood stream by a thin, semipermeable membrane that permits passage of small molecules such as glucose and insulin, while excluding lymphocytes and antibodies involved in immune rejection. 12 It is therefore possible to use islets from animals that are more readily available than human islets. Moreover, since type I diabetes may be an autoimmune disease, the semipermeable membrane also protects islets from potential autoimmune attack after transplantation in a diabetic host. Recent results of segmental From the Departments of Biochemistry and Medicine (Y.A
Injectable microencapsulated islet cells as a bioartificial pancreas
Applied Biochemistry and Biotechnology, 1984
Rat islets encapsulated in semipermeable membranes remained viable in culture for 4 months. Multiple allotransplants of islets encapsulated in alginate-polylysine-polyethyleneimine membranes restored normoglycemia in recipient diabetic rats for most of a 90-day experimental period. Each individual transplant restored normal fasting plasma glucose levels for 15-20 d. The failure of the encapsulated islets was caused by an inflammatory response induced by polyethyleneimine. In contrast a single transplant of islets encapsulated in a biocompatible alginate-polylysine-alginate membrane restored normogtycemia in recipient animals for up to 10 months. Capsules with intact membranes and containing viable islets were recovered from the abdominal cavity 5 months post-transplantation. SEM studies on capsule membranes revealed essentially smooth surfaces. Differences between wet and dry wall thicknesses indicated that the membrane is a hydrogel, 4.00 + 0.28 ~m thick in an aqueous environment.
2006
This paper presents the concept and most of the research undertaken all over the world for the development of a bio-artificial pancreas (BAP) device over the last 30 years. The devices studied, meant to mimic the insulin secretion of the natural organ, were diverse and have been reviewed. Allogeneic or xenogeneic cells or cell clusters have been separated from the host's immune system by synthetic biocompatible semipermeable membranes to prevent the need, of the host, for immune-suppressing regimens. The biocompatible polymer used as a barrier and its intrinsic characteristics, the cell immobilization or suspension media, the existence or not of coimmobilized molecules or cells, the number of devices used and the implantation site, were addressed.
Artificial Organs, 2003
Silicone rubber hollow fiber membrane produces an ideal gas exchange for long-term ECMO due to nonporous characteristics. The extracapillary type silicone rubber ECMO oxygenator having an ultrathin hollow fiber membrane was developed for pediatric application. The test modules were compared to conventional silicone coiltype ECMO modules. In vitro experiments demonstrated a higher O 2 and CO 2 transfer rate, lower blood flow resistance, and less hemolysis than the conventional silicone coil-type modules. This oxygenator was combined with the Gyro C1E3 centrifugal pump, and three ex vivo experiments were conducted to simulate pediatric V-A ECMO condition. Four day and 6 day experiments were conducted in cases 1 and 2, respectively. Case 3 was a long-term experiment up to 2 weeks. No plasma leakage and stable gas performances were achieved. The plasma free hemoglobin was maintained within a normal range. This compact pump-oxygenator system in conjunction with the Gyro C1E3 centrifugal pump has potential for a hybrid total ECMO system.
Design of Bioartificial Pancreas with Functional Micro/Nano-Based Encapsulation of Islets
Current Pharmaceutical Biotechnology, 2014
Type I diabetes mellitus (TIDM), a devastating health issue in all over the world, has been treated by successful transplantation of insulin secreting pancreatic islets. However, serious limitations such as the requirement of immunosuppressive drugs for recipient patients, side effects as a result of long-term use of drugs, and reduced functionality of islets at the transplantation site remain. Bioartificial pancreas that includes islets encapsulated within semi-permeable membrane has been considered as a promising approach to address these requirements. Many studies have focused on micro or nanobased islet immunoisolation systems and tested the efficacy of encapsulated islets using in vitro and in vivo platforms. In this review, we address current progress and obstacles for the development of a bioartificial pancreas using micro/nanobased systems for encapsulation of islets.
Design of a Bioartificial Pancreas
Pathobiology, 2013
Islet transplantation has been shown to be a viable treatment option for patients afflicted with type 1 diabetes. However, the lack of availablity of human pancreases and the need to use risky immunosuppressive drugs to prevent transplant rejection remain two major obstacles to the routine use of islet transplantation in diabetic patients. Successful development of a bioartificial pancreas using the approach of microencapsulation with perm-selective coating of islets in hydrogels for graft immunoisolation holds tremendous promise for diabetic patients because it has great potential to overcome these two barriers. In this review article, we will discuss the need for a bioartificial pancreas, provide a detailed description of the microencapsulation process, and review the status of the technology in clinical development. We will also critically review the various factors that will need to be taken into consideration in order to achieve the ultimate goal of routine clinical application.
Bioengineering of a functional sheet of islet cells for the treatment of diabetes mellitus
Biomaterials, 2009
The present study was designed to establish a novel tissue engineering approach for diabetes mellitus (DM) by fabricating a tissue sheet composed of pancreatic islet cells for in vivo transplantation. Pancreatic islet cell suspensions were obtained from Lewis rats, and plated onto temperature-responsive culture dishes coated with extracellular matrix (ECM) proteins. After the cells reached confluency, islet cells cultured on laminin-5 coated dishes were successfully harvested as a uniformly spread tissue sheet by lowering the culture temperature to 20 C for 20 min. The functional activity of the islet cell sheets was confirmed by histological examination and Insulin secretion assay prior to in vivo transplantation. Histological examination revealed that the harvested islet cell sheet was comprised of insulin-(76%) and glucagon-(19%) positive cells, respectively. In vivo functionality of the islet cell sheet was maintained even 7 days after transplantation into the subcutaneous space of Lewis rats. The present study describes an approach to generate a functional sheet of pancreatic islet cells on laminin-5 coated temperatureresponsive dishes, which can be subsequently transplanted in vivo. This study serves as the foundation for the creation of a novel cell-based therapy for DM to provide patients an alternative method.
Prolonged survival of transplanted islets of Langerhans encapsulated in a biocompatible membrane
Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, 1984
Prolonged survival of islet ailografts in streptozotocin-induced diabetic rats was achieved by encapsulating individual islets in protective, biocompatible alginate-polylysine-alginate membranes. A single intraperitoneal transplant of encapsulated islets reversed the diabetic state for up to 1 year. In contrast, a single injection of unencapsulated islets was effective for less than 2 weeks. The microencapsulation procedure, by protecting transplanted tissue from the components of the immune system, has great clinical potential in the treatment of diseases requiring organ transplantation, such as diabetes and liver disease.
The Bioartificial Pancreas: Progress and Challenges
Diabetes Technology & Therapeutics, 2005
Diabetes remains a devastating disease, with tremendous cost in terms of human suffering and healthcare expenditures. A bioartificial pancreas has the potential as a promising approach to preventing or reversing complications associated with this disease. Bioartificial pancreatic constructs are based on encapsulation of islet cells with a semipermeable membrane so that cells can be protected from the host's immune system. Encapsulation of islet cells eliminates the requirement of immunosuppressive drugs, and offers a possible solution to the shortage of donors as it may allow the use of animal islets or insulin-producing cells engineered from stem cells. During the past 2 decades, several major approaches for immunoprotection of islets have been studied. The microencapsulation approach is quite promising because of its improved diffusion capacity, and technical ease of transplantation. It has the potential for providing an effective long-term treatment or cure of Type 1 diabetes.
Iranian biomedical journal, 2016
Islet transplantation could be an ideal alternative treatment to insulin therapy for type 1 diabetes Mellitus (T1DM). This clinical and experimental field requires a model that covers problems such as requiring a large number of functional and viable islets, the optimal transplantation site, and the prevention of islet dispersion. Hence, the methods of choice for isolation of functional islets and transplantation are crucial. The present study has introduced an experimental model that overcomes some critical issues in islet transplantation, including in situ pancreas perfusion by digestive enzymes through common bile duct. In comparison with conventional methods, we inflated the pancreas in Petri dishes with only 1 ml collagenase type XI solution, which was followed by hand-picking isolation or Ficoll gradient separation to purify the islets. Then we used a hydrogel composite in which the islets were embedded and transplanted into the peritoneal cavity of the streptozotocin-induced ...