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Maintenance of islet function after in vitro culture is crucial for both transplantation and research. Here we evaluated the effects of encapsulation in alginate fiber on the function of human islets which were distributed by the Alberta Islet Distribution Program. Encapsulated human islets from 15 deceased donors were cultured under 5.5 or 25 mM glucose conditions in vitro. The amounts of C-peptide and glucagon secreted from encapsulated islets into the culture media were measured periodically, and immunohistochemical studies were performed. Encapsulated islets maintained C-peptide and glucagon secretion for more than 75 days in 5 cases; in two cases, their secretion was also successfully detected even on day 180. α- and β-cell composition and β-cell survival in islets were unaltered in the fiber after 75 or 180 days of culture. The encapsulated islets cultured with 5.5 mM glucose, but not those with 25 mM glucose, exhibited glucose responsiveness of C-peptide secretion until day 180. We demonstrate that alginate encapsulation enabled human islets to maintain their viability and glucose responsiveness of C-peptide secretion after long-term in vitro culture, potentially for more than for 180 days.

In this paper, we consider a three-machine permutation flow-shop scheduling problem where the criterion is to minimize the total completion time without idle times subject to the minimum makespan on the second machine. This problem is NP-hard while each of the objective functions alone can be optimized in polynomial time. We develop a branch-and-bound algorithm with effective branching rules and dominance properties which help to reduce the search space. By our computational experiments, the branch-and-bound algorithm is comparable to a recent mixed integer programming solver and, for some kinds of problem instances, the branch-and-bound algorithm outperforms the solver. On the other hand, the computational result would indicate that the hierarchical scheduling problems are essentially hard in both theoretical and computational points of view. doi: 10.1057/palgrave.jots.2602014 Keywords: multicriteria scheduling; hierarchical criteria; flow-shop scheduling; branch-and-bound algorithm

Human pluripotent stem cell (hPSCs) derived-pancreatic islets (hSC-islets) are good candidates for cell replacement therapy for patients with diabetes as substitutes for deceased donor-derived islets, because they are pluripotent and have infinite proliferation potential. Grafted hSC-islets ameliorate hyperglycemia in diabetic mice; however, several weeks are needed to normalize the hyperglycemia. These data suggest hSC-islets require maturation, but their maturation process in vivo is not yet fully understood. In this study, we utilized two kinds of streptozotocin (STZ)-induced diabetes model mice by changing the administration timing in order to examine the time course of maturation of hSC-islets and the effects of hyperglycemia on their maturation. We found no hyperglycemia in immune-compromised mice when hSC-islets had been transplanted under their kidney capsules in advance, and STZ was administered 4 weeks after transplantation. Of note, the blood glucose levels of those mice were stably maintained under 100 mg/dl 10 weeks after transplantation; this is lower than the mouse glycemic set point (120–150 mg/dl), suggesting that hSC-islets control blood glucose levels to the human glycemic set point. We confirmed that gene expression of maturation markers of pancreatic beta cells tended to upregulate during 4 weeks after transplantation. Periodical histological analysis revealed that revascularization was observed as early as 1 week after transplantation, but reinnervation in the grafted hSC-islets was not detected at all, even 15 weeks after transplantation. In conclusion, our hSC-islets need at least 4 weeks to mature, and the human glycemic set point is a good index for evaluating ultimate maturity for hSC-islets in vivo.

Since proper break between office work is helpful in decreasing work-related stress and fatigue, a break space in office is also an important place to create healthy and productive workplace environment. However, there are relatively few studies focused on the break space compared to ones focused on work space. In this study, experiments were carried out to investigate the influence of the break space’s indoor environment on occupants’ psychological and physiological responses. To examine whether change in indoor environment during break positively affect occupants’ responses and productivity, lighting, odor and air movement conditions were intentionally changed before the end of the break. As for the psychological response, there was a possibility that it would be affected when the lighting and air movement were changed. As for brain waves, effects were also observed when lighting and air movement were changed. In terms of productivity, performance was better when the environment was changed than when the environment was left unchanged during breaks. The need for breaks was indicated because the worst results were obtained when the work was done continuously without a break in the first place. The best results were obtained when the environment was changed to generate an odor.

Introduction: Although immunosuppressants are required for current islet transplantation for type 1 diabetic patients, many papers have already reported encapsulation devices for islets to avoid immunological attack. The aim of this study is to determine the optimal number of cells and optimal transplantation site for human iPS-derived islet-like cells encapsulated in alginate fiber using diabetic model mice. Methods: We used a suspension culture system for inducing islet-like cells from human iPS cells throughout the islet differentiation process. Islet-like spheroids were encapsulated in the alginate fiber, and cell transplantation experiments were performed with STZ-induced diabetic NOD/SCID mice. We compared the efficacy of transplanted cells between intraperitoneal and subcutaneous administration of alginate fibers by measuring blood glucose and human C-peptide levels serially in mice. Grafts were analyzed histologically, and gene expression in pancreatic β cells was also compared. Results: We demonstrated the reversal of hyperglycemia in diabetic model mice after intraperitoneal administration of these fibers, but not with subcutaneous ones. Intraperitoneal fibers were easily retrieved without any adhesion. Although we detected human c-peptide in mice plasma after subcutaneous administration of these fibers, these fibers became encased by fibrous tissue. Conclusions: These results suggest that the intraperitoneal space is favorable for islet-like cells derived from human iPS cells when encapsulated in alginate fiber. Keywords: iPS cells, islet, Pancreatic β cell, Alginate

Introduction: To complement islet transplantation for type1 diabetic patients, cell-based therapy using pluripotent stem cells such as ES cells and iPS cells is promising. Many papers have already reported the induction of pancreatic β cells from these cell types, but a suspension culture system has not usually been employed. The aim of this study is to establish a suspension culture method for inducing functional islet-like cells from human iPS cells. Methods: We used 30 ml spinner type culture vessels for human iPS cells throughout the differentiation process. Differentiated cells were analyzed by immunostaining and C-peptide secretion. Cell transplantation experiments were performed with STZ-induced diabetic NOD/SCID mice. Blood human C-peptide and glucagon levels were measured serially in mice, and grafts were analyzed histologically. Results: We obtained spherical pancreatic beta-like cells from human iPS cells and detected verifiable amounts of C-peptide secretion in vitro. We demonstrated reversal of hyperglycemia in diabetic model mice after transplantation of these cells, maintaining non-fasting blood glucose levels along with the human glycemic set point. We confirmed the secretion of human insulin and glucagon dependent on the blood glucose level in vivo. Immunohistological analysis revealed that grafted cells became α, β and δ cells in vivo. Conclusions: These results suggest that differentiated cells derived from human iPS cells grown in suspension culture mature and function like pancreatic islets in vivo. Keywords: iPS cells, Islet, Pancreatic β cell

Thin and compliant conductive materials and electronic devices that are able to stand as free-standing membranes or to conform to surfaces are relevant for the development of human-device interfaces and unperceivable skin-contact personal health monitoring systems. In this work, a roll-to-roll (R2R) process for the preparation of conductive polymer nanosheets on large areas has been developed in view to move such technology towards real-world applications. R2R conductive nanosheets are obtained as free-standing structures through release from a temporary substrate and then transferred in conformal contact with any target surface with arbitrary shape, curvature and surface topography (including biological tissue such as skin). A specific high-conductivity formulation of PEDOT:PSS has been optimized for skin-contact applications, by making use of butylene glycol (BG) as a dopant: a dermatologically approved ingredient. The R2R nanosheets were tested as unperceivable surface electromyography electrodes able to record muscle-electrical activity. The present R2R process has advantageous properties such as continuous, high throughput printing on large area rolls, cost-effectiveness, speed of execution and use of industry-ready/mass-scale manufacturing technology. [ABSTRACT FROM AUTHOR]

Diabetes mellitus is caused by breakdown of blood glucose homeostasis, which is maintained by an exquisite balance between insulin and glucagon produced respectively by pancreatic beta cells and alpha cells. However, little is known about the mechanism of inducing glucagon secretion from human alpha cells. Many methods for generating pancreatic beta cells from human pluripotent stem cells (hPSCs) have been reported, but only two papers have reported generation of pancreatic alpha cells from hPSCs. Because NKX6.1 has been suggested as a very important gene for determining cell fate between pancreatic beta and alpha cells, we searched for the factors affecting expression of NKX6.1 in our beta cell differentiation protocols. We found that BMP antagonism and activation of retinoic acid signaling at stage 2 (from definitive endoderm to primitive gut tube) effectively suppressed NKX6.1 expression at later stages. Using two different hPSCs lines, treatment with BMP signaling inhibitor (LDN193189) and retinoic acid agonist (EC23) at Stage 2 reduced NKX6.1 expression and allowed differentiation of almost all cells into pancreatic alpha cells in vivo after transplantation under a kidney capsule. Our study demonstrated that the cell fate of pancreatic cells can be controlled by adjusting the expression level of NKX6.1 with proper timing of BMP antagonism and activation of retinoic acid signaling during the pancreatic differentiation process. Our method is useful for efficient induction of pancreatic alpha cells from hPSCs.