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

Raza Ali Naqvi, Afsar Raza Naqvi, Amar Singh, Medha Priyadarshini, Appakalai N. Balamurugan, Brian T. Layden

Research output: Contribution to journalReview articlepeer-review

9 Scopus citations

Abstract

Replacement of β 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 β cell approaches are also gaining momentum and may hold promise to yield a significant supply of insulin-producing cells. Theoretically, personalized β cells derived from a patient’s iPSCs is one exciting approach, but β cell-specific immunity in T1D recipients would still be a challenge. In this context, encapsulation studies on both pig islet as well as iPSC–β 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.

Original languageEnglish (US)
Article number1001041
JournalFrontiers in Endocrinology
Volume13
DOIs
StatePublished - Jan 5 2023

Bibliographical note

Funding Information:
This work is funded by a grant from Wach Fund, College of Dentistry, University of Illinois at Chicago.

Publisher Copyright:
Copyright © 2023 Naqvi, Naqvi, Singh, Priyadarshini, Balamurugan and Layden.

Keywords

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

PubMed: MeSH publication types

  • Journal Article
  • Review
  • Research Support, Non-U.S. Gov't

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