Stem cell-based approaches to solving the problem of tissue supply for islet tra

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Cale N. Street a, Simonetta Sipione b, Lisa Helmsa, Tanya Binette a,
4 j& Y  u3 k. x; ?1 _6 DRay V. Rajotte a, R. Chris Bleackley b, Gregory S. Korbutt a,∗
3 d5 K; F( ]/ S7 P/ o$ H: _a Surgical-Medical Research Institute, University of Alberta, Room 1074, Dentistry/Pharmacy Building, Edmonton, Alta., Canada T6G 2N8, G4 [. k, K1 ^; g9 r
b Department of Biochemistry, University of Alberta, 4-60 Medical-Sciences Building, Edmonton, Alta., Canada T6G 2S7
; ^3 l8 E, q+ t+ B4 T& wReceived 13 August 2003; accepted 16 September 2003
  {6 l7 h3 E+ {4 V; ^" {Abstract2 |, M, o: M, P6 Z: _' b. d
Type 1 diabetes is a debilitating condition, affecting millionsworldwide, that is characterized by the autoimmune destruction
4 F  f3 m4 Y4 t4 U8 _of insulin-producing pancreatic islets of Langerhans. Although exogenous insulin administration has traditionally been the
7 S9 l# l! [' N5 Q& F, Y- C, jmode of treatment for this disease, recent advancements in the transplantation of donor-derived insulin-producing cells have3 A$ I4 q1 b0 ^0 }( u8 V! m
provided new hope for a cure. However, in order for islet transplantation to become a widely used technique, an alternative
1 v8 E3 ?% d" m! G2 L  x: ?source of cells must be identified to supplement the limited supply currently available from cadaveric donor organs. Stem
5 d6 q# K( v* \# @- ]cells represent a promising solution to this problem, and current research is being aimed at the creation of islet-endocrine
- v0 c0 y: c0 j* q0 `6 ^tissue from these undifferentiated cells. This review presents a summary of the research to date involving stem cells and cell
( \7 F# D' g; Y+ [9 lreplacement therapy for type 1 diabetes. The potential for the differentiation of embryonic stem (ES) cells to islet phenotype# Y( w& c$ |+ y8 {4 F% f
is discussed, as well as the possibility of identifying and exploiting a pancreatic progenitor/stem cell from the adult pancreas.  E  ], t% m. p8 W5 P% N
The possibility of creating new islets from adult stem cells derived from other tissues, or directly form other terminally
( q+ m- P6 c; M+ I% O6 Pdifferentiated cell types is also addressed. Finally, a model for the isolation and maturation of islets from the neonatal porcine
$ X( p3 S+ d' r% D% ypancreas is discussed as evidence for the existence of an islet precursor cell in the pancreas.$ d9 r; s1 h0 ?- w
© 2003 Elsevier Ltd. All rights reserved.
) S- I" |9 y& ZKeywords: Stem cells; Type 1 diabetes; Islet transplantation; Differentiation; Xenotransplantation* ?; L' p. t5 N) I8 Y

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