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Review
. 2011 Feb;16(1):76-82.
doi: 10.1097/MOT.0b013e32834252b5.

Stem cell-derived islet cells for transplantation

Juan Domínguez-Bendala  1 , Luca Inverardi, Camillo Ricordi
Affiliations
Review

Stem cell-derived islet cells for transplantation

Juan Domínguez-Bendala et al. Curr Opin Organ Transplant. 2011 Feb.

Abstract

Purpose of review: The promise of islet transplantation for type 1 diabetes has been hampered by the lack of a renewable source of insulin-producing cells. However, steadfast advances in the field have set the stage for stem cell-based approaches to take over in the near future. This review focuses on the most intriguing findings reported in recent years, which include not only progress in adult and embryonic stem cell differentiation, but also the direct reprogramming of nonendocrine tissues into insulin-producing beta cells.

Recent findings: In spite of their potential for tumorigenesis, human embryonic stem (hES) cells are poised to be in clinical trials within the next decade. This situation is mainly due to the preclinical success of a differentiation method that recapitulates beta cell development. In contrast, adult stem cells still need one such gold standard of differentiation, and progress is somewhat impeded by the lack of consensus on the best source. A concerted effort is necessary to bring their potential to clinical fruition. In the meantime, reported success in reprogramming might offer a 'third way' towards the rescue of pancreatic endocrine function.

Summary: Here we discuss the important strategic decisions that need to be made in order to maximize the therapeutic chances of each of the presented approaches.

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Figures

Figure 1
Figure 1
Gartner innovation curve representing the defining steps of the evolution of clinical islet transplantation.
Figure 2
Figure 2
Gartner innovation curve representing the key milestones of embryonic stem cell differentiation along the insulin-producing cell lineage.
See this image and copyright information in PMC

References

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    1. Shapiro AM, Lakey JR, Ryan EA, Korbutt GS, Toth E, Warnock GL, et al. Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen. N Engl J Med. 2000;343(4):230–238. (**) This is the first report on long-term islet function in humans. It was based on a steroid-free immunosuppressive regimen (the “Edmonton protocol”). Anti-rejection drugs used prior to this clinical breakthrough usually resulted in graft death shortly after transplantation.

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