Treatment of diabetes by xenogeneic islets without immunosuppression. Use of a vascularized bioartificial pancreas

Maki, Takashi; Otsu, I.; O’Neil, John J.; Dunleavy, Karen; Mullon, Claudy; Solomon, Barry A.; Monaco, Anthony P.

doi:10.2337/diabetes.45.3.342

Cited by 55 publications

(40 citation statements)

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“…Recent approaches have made progress by placing cells into hollow fiber bioreactors or encapsulating membranes as a means to deliver cell activities to a patient. Extracorporeal liver-assist devices and encapsulated Islet of Langerhans to treat liver failure and diabetes mellitus are the most notable examples (50,51). A reasonable extension of this approach is to add cell therapy to the current renal substitution processes of hemodialysis and hemofiltration in the acute renal failure state.…”

Section: Discussionmentioning

confidence: 99%

Bioartificial Kidney Ameliorates Gram-Negative Bacteria-Induced Septic Shock in Uremic Animals

Fissell

Lou

Abrishami

et al. 2003

Journal of the American Society of Nephrology

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Abstract. The bioartificial kidney (BAK) consists of a conventional hemofiltration cartridge in series with a renal tubule assist device (RAD) containing 10 9 porcine renal proximal tubule cells. BAK replaces filtration, transport, and metabolic and endocrinologic activities of a kidney. Previous work in an acutely uremic dog model demonstrated that BAK ameliorated endotoxin (lipopolysaccharide [LPS])-induced hypotension and altered plasma cytokine levels. To further assess the role of BAK in sepsis in acute renal failure, dogs were nephrectomized and 48 h later administered intraperitoneally with 30 ϫ 10 10 bacteria/kg of E. coli. One hour after bacterial administration, animals were placed in a continuous venovenous hemofiltration circuit with either a sham RAD without cells (n ϭ 6) or a RAD with cells (n ϭ 6). BP, cardiac output, heart rate, pulmonary capillary wedge pressure, and systemic vascular resistance were measured throughout the study. All animals tested were in renal failure, with blood urea nitrogen and serum creatinine concentrations greater than 60 and 6 mg/dl, respectively. RAD treatment maintained significantly better cardiovascular performance, as determined by arterial BP (P Ͻ 0.05) and cardiac output (P Ͻ 0.02), for longer periods than sham RAD therapy. Consistently, all sham RAD-treated animals, except one, expired within 2 to 9 h after bacterial administration, whereas all RAD-treated animals survived more than 10 h. Plasma levels of TNF-␣, IL-10, and C-reactive protein (CRP) were measured during cell RAD and sham RAD treatment. IL-10 levels were significantly higher (P Ͻ 0.01) during the entire treatment interval in the RAD animals compared with sham controls. These data demonstrated in a pilot large animal experiment that the BAK with RAD altered plasma cytokine levels in acutely uremic animals with septic shock. This change was associated with improved cardiovascular performance and increased survival time. These results demonstrate that the addition of cell therapy to hemofiltration in an acutely uremic animal model with septic shock ameliorates cardiovascular dysfunction, alters systemic cytokine balance, and improves survival time.

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Section: Discussionmentioning

confidence: 99%

Bioartificial Kidney Ameliorates Gram-Negative Bacteria-Induced Septic Shock in Uremic Animals

Fissell

Lou

Abrishami

et al. 2003

Journal of the American Society of Nephrology

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“…The encapsulation systems utilize materials that are permeable enough to allow the diffusion of glucose and other nutrients to the islets, and the diffusion of waste and insulin away from the islets, while masking the islets from the host immune response. [3][4][5][6] Alginate is a chemically inert nondegradable polymer, and most importantly it has the capability to immunoisolate encapsulated cells. 7 A simple and commonly used method to ensure whether alginate encapsulation provides sufficient immunoisolation for many cell types is the application of a polycationic coating, followed by an alginate coating.…”

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confidence: 99%

Alginate Encapsulation of Human Embryonic Stem Cells to Enhance Directed Differentiation to Pancreatic Islet-Like Cells

Richardson

Kumta

Banerjee

2014

Tissue Engineering Part A

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The pluripotent property of human embryonic stem cells (hESCs) makes them attractive for treatment of degenerative diseases such as diabetes. We have developed a stage-wise directed differentiation protocol to produce alginate-encapsulated islet-like cells derived from hESCs, which can be directly implanted for diabetes therapy. The advantage of alginate encapsulation lies in its capability to immunoisolate, along with the added possibility of scalable culture. We have evaluated the possibility of encapsulating hESCs at different stages of differentiation. Encapsulation of predifferentiated cells resulted in insufficient cellular yield and differentiation. On the other hand, encapsulation of undifferentiated hESCs followed by differentiation induction upon encapsulation resulted in the highest viability and differentiation. More striking was that alginate encapsulation resulted in a much stronger differentiation compared to parallel two-dimensional cultures, resulting in 20-fold increase in c-peptide protein synthesis. To elucidate the mechanism contributing to encapsulation-mediated enhancement in hESC maturation, investigation of the signaling pathways revealed interesting insight. While the phospho-protein levels of all the tested signaling molecules were lower under encapsulation, the ratio of pSMAD/pAKT was significantly higher, indicating a more efficient signal transduction under encapsulation. These results clearly demonstrate that alginate encapsulation of hESCs and differentiation to islet-cell types provides a potentially translatable treatment option for type 1 diabetes.

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“…In 1991, Brunetti et al transplanted microcapsulated porcine islets into spontaneous diabetic dogs with IDDM in which only one of five dogs showed complete reversal from hyperglycemia [1]. In 1996, Maki et al transplanted porcine islets into total pancreatectomized dogs [21,22]. Only two of the seventeen dogs maintained good glycemic control for 8 months, but all dogs required a small amount of daily insulin administration to maintain normoglycemia.…”

Section: Discussionmentioning

confidence: 99%

Xenotransplantation of Porcine Pancreatic Endocrine Cells to Total Pancreatectomized Dogs

Edamura

Itakura

Nasu

et al. 2003

The Journal of Veterinary Medical Science

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ABSTRACT. Xenotransplantation of porcine pancreatic endocrine (PE) cells in a diffusion chamber, a bioartificial endocrine pancreas (Bio-AEP), was conducted to total pancreatectomized dogs. Six pancreatectomized dogs were divided into two groups of 3 dogs each. In three dogs of the control group, exogenous insulin was administered twice a day for 30 weeks to maintain fasting blood glucose (FBG) levels within the normal range. The remaining three dogs were implanted with Bio-AEPs (implantation group), in addition to daily insulin administration. In the implantation group, Bio-AEPs containing 1.3 to 1.8 × 10 7 cells per kg of body weight of the recipient were implanted without fixation into the abdominal cavity. In the control group, exogenous insulin requirements did not decrease during the experimental period, whereas it significantly decreased for a certain period (3, 11, 17 weeks) after implantation in all implanted dogs. In the implantation group, laparotomy was performed after FBG and the exogenous insulin requirement increased again and Bio-AEPs were removed. Two Bio-AEPs were completely destroyed, and the remaining one was encapsulated by thin fibrous tissue. In this dog, effusion was present within the capsule, but the Bio-AEP was not destroyed. Histopathologically, the necrosis, presumably caused by hypoxia, of the PE-cells was observed on transmission electron microscopy. In conclusion, Bio-AEP could function for a certain period after implantation in this study. However, more preclinical researches should be needed to apply this technique for the treatme nt of diabetic dogs.

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Treatment of diabetes by xenogeneic islets without immunosuppression. Use of a vascularized bioartificial pancreas

Cited by 55 publications

References 0 publications

Bioartificial Kidney Ameliorates Gram-Negative Bacteria-Induced Septic Shock in Uremic Animals

Bioartificial Kidney Ameliorates Gram-Negative Bacteria-Induced Septic Shock in Uremic Animals

Alginate Encapsulation of Human Embryonic Stem Cells to Enhance Directed Differentiation to Pancreatic Islet-Like Cells

Xenotransplantation of Porcine Pancreatic Endocrine Cells to Total Pancreatectomized Dogs

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