Proliferation of Pancreatic Endocrine Cells Using Disaggregation–Expansion–Reaggregation Technology in Isolated Rat Islets

Jeong, Jin Ho; Lee, Jeong Ki; Ju, Man Ki; Joo, Dong Jin; Huh, Kyu Ha; Kim, M.S.; Kim, J.Y.; Cho, Y.; Kim, Y.S.

doi:10.1016/j.transproceed.2010.02.044

Cited by 9 publications

(1 citation statement)

References 8 publications

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“…47 Future strategies for increasing the infection efficiency could include dissociation of islets, infection and expansion, then re-aggregation before transplantation, or the use of an alternative, non-viral DNA delivery system, such as gold nanoparticles, that infect the whole islets rather than merely the mantle. 48,49 One concern with this approach is the uncontrolled expression of cell cycle genes, leading to the formation of tumors. While this is a consideration for long-term culture of permanently mutated cells, the use of a transient non-incorporating adenovirus lessens these concerns in the experiments shown here.…”

Section: Discussionmentioning

confidence: 99%

Overexpression ofE2F3promotes proliferation of functional human β cells without induction of apoptosis

et al. 2013

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The mechanisms that control proliferation, or lack thereof, in adult human β cells are poorly understood. Controlled induction of proliferation could dramatically expand the clinical application of islet cell transplantation and represents an important component of regenerative approaches to a functional cure of diabetes. Adult human β cells are particularly resistant to common proliferative targets and often dedifferentiate during proliferation. Here we show that expression of the transcription factor E2F3 has a role in regulating β-cell quiescence and proliferation. We found human islets have virtually no expression of the pro-proliferative G 1/S transcription factors E2F1-3, but an abundance of inhibitory E2Fs 4-6. In proliferative human insulinomas, inhibitory E2Fs were absent, while E2F3 is expressed. Using this pattern as a "roadmap" for proliferation, we demonstrated that ectopic expression of nuclear E2F3 induced significant expansion of insulin-positive cells in both rat and human islets. These cells did not undergo apoptosis and retained their glucose-responsive insulin secretion, showing the ability to reverse diabetes in mice. Our results suggest that E2F4-6 may help maintain quiescence in human β cells and identify E2F3 as a novel target to induce proliferation of functional β cells. Refinement of this approach may increase the islets available for cell-based therapies and research and could provide important cues for understanding in vivo proliferation of β cells.

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Section: Discussionmentioning

confidence: 99%

Overexpression ofE2F3promotes proliferation of functional human β cells without induction of apoptosis

et al. 2013

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

Sun

Wang

et al. 2017

Biotech and App Biochem

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After islet isolation, diffusion has become the main mechanism to transport oxygen and nutrients into the core of islets. However, diffusion has limitations, by which nutrients cannot effectively reach the core of large islets and can eventually cause core cell death and islet loss. This problem can be resolved by dispersing islets into single islet cells, but single islet cells do not exhibit insulin release function in in vitro culture. In this study, we intended to establish a new islet engineering approach by forming islet cell clusters to improve islet survival and function. Therefore, alginate gels were used to encapsulate islet cells to form artificial islets after dispersion of islets into single cells. The shape of the islet cell clusters was similar to native islets, and the size of the islet cell clusters was limited to a maximum diameter of 100 μm. By limiting the diameter of this engineered islet cell cluster, cell viability was nearly 100%, a significant improvement over natural islets. Importantly, islet cell clusters express the genes of islets, including Isl-1, Gcg, and insulin-1, and insulin secretion ability was maintained in vitro.

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Silk matrices promote formation of insulin-secreting islet-like clusters

et al. 2016

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Proliferation of Pancreatic Endocrine Cells Using Disaggregation–Expansion–Reaggregation Technology in Isolated Rat Islets

Cited by 9 publications

References 8 publications

Overexpression ofE2F3promotes proliferation of functional human β cells without induction of apoptosis

Overexpression ofE2F3promotes proliferation of functional human β cells without induction of apoptosis

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

Silk matrices promote formation of insulin-secreting islet-like clusters

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