Dataset Information

β Cell replacement: improving on the design.

ABSTRACT:

Purpose of review

Here we summarize recent advancements in β cell replacement as a therapy for type 1 diabetes.

Recent findings

β cell replacement therapy has been proposed as a cure for type 1 diabetes with the introduction of the Edmonton protocol for cadaveric islet transplantation. To allow widespread use of this approach, efforts have focused on establishing an abundant source of insulin-producing β cells, protecting transplanted cells from ischemia-mediated death, immune rejection, and re-occurring autoimmunity. Recent developments addressing these issues include generation of insulin-producing cells from human pluripotent stem cells, different encapsulation strategies and prevention of ischemia upon transplant.

Summary

Despite significant advances in generating functional β cells from human pluripotent stem cells, several key challenges remain in regard to the survival of β cell grafts, protection from (auto-) immune destruction and implementation of additional safety mechanisms before a stem cell-based cell replacement therapy approach can be widely applied. Taking current findings into consideration, we outline a multilayered approach to design immune-privileged β cells from stem cells using state of the art genome editing technologies that if successfully incorporated could result in great benefit for diabetic patients and improve clinical results for cell replacement therapy.

SUBMITTER: Castro-Gutierrez R

PROVIDER: S-EPMC8815310 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

β Cell replacement: improving on the design.

Castro-Gutierrez Roberto R Michels Aaron W AW Russ Holger A HA

Current opinion in endocrinology, diabetes, and obesity 20180801 4

<h4>Purpose of review</h4>Here we summarize recent advancements in β cell replacement as a therapy for type 1 diabetes.<h4>Recent findings</h4>β cell replacement therapy has been proposed as a cure for type 1 diabetes with the introduction of the Edmonton protocol for cadaveric islet transplantation. To allow widespread use of this approach, efforts have focused on establishing an abundant source of insulin-producing β cells, protecting transplanted cells from ischemia-mediated death, immune rej ...[more]

PMID: 29846237

Similar Datasets

Project description:Β-glucosidases are key enzymes used in second-generation biofuel production. They act in the last step of the lignocellulose saccharification, converting cellobiose in glucose. However, most of the β-glucosidases are inhibited by high glucose concentrations, which turns it a limiting step for industrial production. Thus, β-glucosidases have been targeted by several studies aiming to understand the mechanism of glucose tolerance, pH and thermal resistance for constructing more efficient enzymes. In this paper, we present a database of β-glucosidase structures, called Glutantβase. Our database includes 3842 GH1 β-glucosidase sequences collected from UniProt. We modeled the sequences by comparison and predicted important features in the 3D-structure of each enzyme. Glutantβase provides information about catalytic and conserved amino acids, residues of the coevolution network, protein secondary structure, and residues located in the channel that guides to the active site. We also analyzed the impact of beneficial mutations reported in the literature, predicted in analogous positions, for similar enzymes. We suggested these mutations based on six previously described mutants that showed high catalytic activity, glucose tolerance, or thermostability (A404V, E96K, H184F, H228T, L441F, and V174C). Then, we used molecular docking to verify the impact of the suggested mutations in the affinity of protein and ligands (substrate and product). Our results suggest that only mutations based on the H228T mutant can reduce the affinity for glucose (product) and increase affinity for cellobiose (substrate), which indicates an increment in the resistance to product inhibition and agrees with computational and experimental results previously reported in the literature. More resistant β-glucosidases are essential to saccharification in industrial applications. However, thermostable and glucose-tolerant β-glucosidases are rare, and their glucose tolerance mechanisms appear to be related to multiple and complex factors. We gather here, a set of information, and made predictions aiming to provide a tool for supporting the rational design of more efficient β-glucosidases. We hope that Glutantβase can help improve second-generation biofuel production. Glutantβase is available at http://bioinfo.dcc.ufmg.br/glutantbase .

Dataset Information

β Cell replacement: improving on the design.

Purpose of review

Recent findings

Summary

Publications

β Cell replacement: improving on the design.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets