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The future treatment for type 1 diabetes: Pig islet- or stem cell-derived β cells?

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FRONTIERS IN ENDOCRINOLOGY
卷 13, 期 -, 页码 -

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FRONTIERS MEDIA SA
DOI: 10.3389/fendo.2022.1001041

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adult pig islets (API); neonatal pig islets (NPIs); maximum survival time (MST); gal knockout (GTKO) pigs; microencapsulation; instant blood-mediatedinflammatory reaction (IBMIR); stem cell derived beta cells

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Replacement of beta cells and induction of pluripotent stem cells hold promise for curing type 1 diabetes, but challenges need to be resolved cautiously.
Replacement of beta cells is only a curative approach for type 1 diabetes (T1D) patients to avoid the threat of iatrogenic hypoglycemia. In this pursuit, islet allotransplantation under Edmonton's protocol emerged as a medical miracle to attain hypoglycemia-free insulin independence in T1D. Shortage of allo-islet donors and post-transplantation (post-tx) islet loss are still unmet hurdles for the widespread application of this therapeutic regimen. The long-term survival and effective insulin independence in preclinical studies have strongly suggested pig islets to cure overt hyperglycemia. Importantly, CRISPR-Cas9 technology is pursuing to develop humanized pig islets that could overcome the lifelong immunosuppression drug regimen. Lately, induced pluripotent stem cell (iPSC)-derived beta cell approaches are also gaining momentum and may hold promise to yield a significant supply of insulin-producing cells. Theoretically, personalized beta cells derived from a patient's iPSCs is one exciting approach, but beta cell-specific immunity in T1D recipients would still be a challenge. In this context, encapsulation studies on both pig islet as well as iPSC-beta cells were found promising and rendered long-term survival in mice. Oxygen tension and blood vessel growth within the capsules are a few of the hurdles that need to be addressed. In conclusion, challenges associated with both procedures, xenotransplantation (of pig-derived islets) and stem cell transplantation, are required to be cautiously resolved before their clinical application.

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