Engineering islet for improved performance by optimized reaggregation in alginate gel beads

Li, Na; Sun, Guangwei; Wang, Shujun; Wu, Yu; Xiu, Zhilong; Sun, Dongsheng; Guo, Xin; Zhang, Ying; Ma, Xiaojun

doi:10.1002/bab.1489

Cited by 9 publications

(7 citation statements)

References 23 publications

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“…This is of particular relevance because it has long been thought that size is a critical component to islet function, and pseudoislet dimensions must be comparable to intact islets for proper hormone secretion (14,16–18,22,25,38). Although large pseudoislets have been used in transplantation and β-cell mass replacement studies, this model can also be used to interrogate the function of the other islet cell types.…”

Section: Discussionmentioning

confidence: 99%

Reestablishment of Glucose Inhibition of Glucagon Secretion in Small Pseudoislets

Reissaus

Piston

2017

Diabetes

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Misregulated hormone secretion from the islet of Langerhans is central to the pathophysiology of diabetes. Although insulin plays a key role in glucose regulation, the importance of glucagon is increasingly acknowledged. However, the mechanisms that regulate glucagon secretion from α-cells are still unclear. We used pseudoislets reconstituted from dispersed islet cells to study α-cells with and without various indirect effects from other islet cells. Dispersed islet cells secrete aberrant levels of glucagon and insulin at basal and elevated glucose levels. When cultured, murine islet cells reassociate to form pseudoislets, which recover normal glucose-regulated hormone secretion, and human islet cells follow a similar pattern. We created small (∼40-µm) pseudoislets using all of the islet cells or only some of the cell types, which allowed us to characterize novel aspects of regulated hormone secretion. The recovery of regulated glucagon secretion from α-cells in small pseudoislets depends upon the combined action of paracrine factors, such as insulin and somatostatin, and juxtacrine signals between EphA4/7 on α-cells and ephrins on β-cells. Although these signals modulate different pathways, both appear to be required for proper inhibition of glucagon secretion in response to glucose. This improved understanding of the modulation of glucagon secretion can provide novel therapeutic routes for the treatment of some individuals with diabetes.

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Section: Discussionmentioning

confidence: 99%

Reestablishment of Glucose Inhibition of Glucagon Secretion in Small Pseudoislets

Reissaus

Piston

2017

Diabetes

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“…Alginate as a 3D culture platform was, for instance, used for reaggregation of dispersed single islet cells with the intention of creating similar-sized islets, in order to overcome the problem of oxygen diffusion due to the wide size range in human islets. 36 Collagen is the main structural protein for most tissues and has often been investigated due to its good mechanical properties. 37 Many biological scaffold materials incorporating collagen are biologically active and show therefore good cell adhesion and proliferation properties.…”

Section: Scaffold Materialsmentioning

confidence: 99%

The emerging field of pancreatic tissue engineering: A systematic review and evidence map of scaffold materials and scaffolding techniques for insulin-secreting cells

et al. 2019

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A bioartificial endocrine pancreas is proposed as a future alternative to current treatment options. Patients with insulin-secretion deficiency might benefit. This is the first systematic review that provides an overview of scaffold materials and techniques for insulin-secreting cells or cells to be differentiated into insulin-secreting cells. An electronic literature survey was conducted in PubMed/MEDLINE and Web of Science, limited to the past 10 years. A total of 197 articles investigating 60 different materials met the inclusion criteria. The extracted data on materials, cell types, study design, and transplantation sites were plotted into two evidence gap maps. Integral parts of the tissue engineering network such as fabrication technique, extracellular matrix, vascularization, immunoprotection, suitable transplantation sites, and the use of stem cells are highlighted. This systematic review provides an evidence-based structure for future studies. Accumulating evidence shows that scaffold-based tissue engineering can enhance the viability and function or differentiation of insulin-secreting cells both in vitro and in vivo.

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“…It is possible to artificially organize the islets in alginate gels into clusters mimicking natural islets [47].…”

Section: +mentioning

confidence: 99%

Avoiding Immunosuppression for Islet Transplantation: Use of Protective Biomaterials

Alexander¹,

Nguyen²,

Flores³

et al. 2017

Challenges in Pancreatic Pathology

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Islet transplantation, with the advent of the Edmonton protocol in 2000, has offered a significant alternative for long-lasting treatment of type 1 diabetes. However, the immunosuppression required for transplantation has the cytotoxic effect on pancreatic islets, and thus limiting the long-term efficacy of the transplant. Immediate loss of islets after transplant was also observed because of immediate blood-mediated inflammatory response (IBMIR), which kills islets transplanted in the liver through portal vein. There is also commonly a lack of microvascular blood supply to the transplanted islets. In this chapter, we will review the variety of technologies used to protect transplanted islets against toxicity of immunosuppression, immune rejection, and inflammatory response. We will evaluate the mechanisms of these technologies and their progress in solving the challenges to islet transplantation. The technologies include encapsulation of transplanted islets in various polymers, transplants in sites other than the liver, and creation of new prevascularized transplant site. These technologies offer several mechanisms to prevent immune rejection or immediate contact with cytotoxic inflammatory response, in addition to maintaining islet integrity. New transplant sites are also being developed to support the islets, by allowing establishment of microvasculature and innervation, prior to addition of the islets.

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Engineering islet for improved performance by optimized reaggregation in alginate gel beads

Cited by 9 publications

References 23 publications

Reestablishment of Glucose Inhibition of Glucagon Secretion in Small Pseudoislets

Reestablishment of Glucose Inhibition of Glucagon Secretion in Small Pseudoislets

The emerging field of pancreatic tissue engineering: A systematic review and evidence map of scaffold materials and scaffolding techniques for insulin-secreting cells

Avoiding Immunosuppression for Islet Transplantation: Use of Protective Biomaterials

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