Strategies to Combat Hypoxia in Encapsulated Islet Transplantation

Krishnan, Rahul; Ko, David; Tucker, Tori; Opara, Emmanuel C.; Foster, Clarence E.; Imagawa, David K.; Stamos, Michael J.; Lakey, Jonathan R. T.

doi:10.4172/2161-1076.1000259

Cited by 10 publications

(7 citation statements)

References 60 publications

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“…Moreover, both the MIN6 aggregates and composite aggregates (80–100 µm) are smaller than 150 µm, which is the size of the islets recommended for transplantation due to their higher viability, higher functionality, and greater oxygen consumption. 34 In addition, our composite aggregates perform very well in terms of insulin secretion and show higher insulin content than pure MIN6 aggregates, indicating also their viability, although they consist of a higher number of cells (approximately 1750 cells). Ichihara et al 35 showed that pseudo-islets prepared using 4600 cells had less than 2% of apoptotic cells, as expected mainly in the central core.…”

Section: Discussionmentioning

confidence: 69%

Endothelial and beta cell composite aggregates for improved function of a bioartificial pancreas encapsulation device

et al. 2018

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Introduction:Encapsulation of pancreatic islets or beta cells is a promising strategy for treatment of type 1 diabetes by providing an immune isolated environment and allowing for transplantation in a different location than the liver. However, islets used for encapsulation often show lower functionality due to the damaging of islet endothelial cells during the isolation procedure. Factors produced by endothelial cells have great impact on beta cell insulin secretion. Therefore, mutual signaling between endothelial cells and beta cells should be considered for the development of encapsulation systems to achieve high insulin secretion and maintain beta cell viability. Here, we investigate whether co-culture of beta cells with endothelial cells could improve beta cell function within encapsulation devices.Materials and methods:Mouse insulinoma MIN6 cells and human umbilical vein endothelial cells were used for creating composite aggregates on agarose microwell platform. The composite aggregates were encapsulated within flat poly(ether sulfone)/polyvinylpyrrolidone device. Their functionality was assessed by glucose-induced insulin secretion test and compared to non-encapsulated free-floating aggregates.Results:We created composite aggregates of 80–100 µm in diameter, closely mimicking pancreatic islets. Upon glucose stimulation, their insulin secretion is improved in comparison to aggregates consisting of only MIN6 cells. Moreover, the composite aggregates encapsulated within a device secrete more insulin than aggregates consisting of only MIN6 cells.Conclusion:Composite aggregates of MIN6 cells with human umbilical vein endothelial cells have improved insulin secretion in comparison to MIN6 aggregates showing that the interaction of beta cell and endothelial cell is crucial for a functional encapsulation system.

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Section: Discussionmentioning

confidence: 69%

Endothelial and beta cell composite aggregates for improved function of a bioartificial pancreas encapsulation device

et al. 2018

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“…Microcapsules have been studied in our group as well as in other groups, and it is known that encapsulated cells are exposed to hypoxia (Khattak et al, ; Krishnan & Ko, ). Our previous study has shown that encapsulated islet using alginate only can improve diabetes by transplantation in mice without immunosuppressants (Park et al, ).…”

Section: Discussionmentioning

confidence: 97%

“…To minimize the fibrotic reaction around alginate capsules, our group used chitosan for the second layer coating on the alginate microcapsules and demonstrated a remarkable decrease in fibrotic reactions (Yang et al, ). Second, hypoxia develops because there is no blood vessel formation in the early stage of transplantation, and oxygen supply to the transplanted encapsulated islets in the peritoneal cavity of the recipient is supplied only by diffusion (Krishnan & Ko, ). The oxygen tension of the peritoneal cavity is approximately 50 mmHg (Renvall & Niinikoski, ).…”

Section: Introductionmentioning

confidence: 99%

Improvement of islet function and survival by integration of perfluorodecalin into microcapsules in vivo and in vitro

Lee

Park

Yang

et al. 2018

J Tissue Eng Regen Med

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Hypoxic injury of islets is a major obstacle for encapsulated islet transplantation into the peritoneal cavity. To improve oxygen delivery to encapsulated islets, we integrated 20% of the oxygen carrier material, perfluorodecalin (PFD), in alginate capsules mixed with islets (PFD-alginate). Integration of PFD clearly improved islet viability and decreased reactive oxygen species production compared to islets encapsulated with alginate only (alginate) and naked islets exposed to hypoxia in vitro. In PFD-alginate capsules, HIF-1α expression was minimal, and insulin expression was well maintained. Furthermore, the best islet function represented by glucose-stimulated insulin secretion was observed for the PFD-alginate capsules in hypoxic condition. For the in vivo study, the same number of naked islets and encapsulated islets (alginate and PFD-alginate) was transplanted into streptozotocin-induced diabetic mice. Nonfasting blood glucose levels and the area under the curve for glucose based on intraperitoneal glucose tolerance tests in the PFD-alginate group were lower than in the alginate group. The harvested islets stained positive for insulin in all groups, but the ratio of dead cell area was 4 times higher in the alginate group than in the PFD-alginate group. In conclusion, integration of PFD in alginate microcapsules improved islet function and survival by minimizing the hypoxic damage of islets after intraperitoneal transplantation.

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“…As discussed, for a controlled rate of reaction, calcium peroxide can be incorporated into hydrophobic polymers. The controlled and sustained presence of oxygen is imperative for the first few weeks to promote cell differentiation and tissue healing 52,115 . The use of liquid peroxides (e.g., hydrogen peroxide) as oxygen carriers has also shown considerable potential in tissue engineering applications.…”

Section: Discussionmentioning

confidence: 99%

Breathing life into engineered tissues using oxygen-releasing biomaterials

et al. 2019

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Engineering three-dimensional (3D) tissues in clinically relevant sizes have demonstrated to be an effective solution to bridge the gap between organ demand and the dearth of compatible organ donors. A major challenge to the clinical translation of tissue-engineered constructs is the lack of vasculature to support an adequate supply of oxygen and nutrients post-implantation. Previous efforts to improve the vascularization of engineered tissues have not been commensurate to meeting the oxygen demands of implanted constructs during the process of homogeneous integration with the host. Maintaining cell viability and metabolic activity during this period is imperative to the survival and functionality of the engineered tissues. As a corollary, there has been a shift in the scientific impetus beyond improving vascularization. Strategies to engineer biomaterials that encapsulate cells and provide the sustained release of oxygen over time are now being explored. This review summarizes different types of oxygen-releasing biomaterials, strategies for their fabrication, and approaches to meet the oxygen requirements in various tissue engineering applications, including cardiac, skin, bone, cartilage, pancreas, and muscle regeneration.

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Strategies to Combat Hypoxia in Encapsulated Islet Transplantation

Cited by 10 publications

References 60 publications

Endothelial and beta cell composite aggregates for improved function of a bioartificial pancreas encapsulation device

Endothelial and beta cell composite aggregates for improved function of a bioartificial pancreas encapsulation device

Improvement of islet function and survival by integration of perfluorodecalin into microcapsules in vivo and in vitro

Breathing life into engineered tissues using oxygen-releasing biomaterials

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