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 X/ t6 B. i7 y/ A' g0 n
Ray V. Rajotte a, R. Chris Bleackley b, Gregory S. Korbutt a,∗: p8 {' v% z6 N+ u1 B5 W/ i+ P
a Surgical-Medical Research Institute, University of Alberta, Room 1074, Dentistry/Pharmacy Building, Edmonton, Alta., Canada T6G 2N8
3 c7 a! V/ U4 M- g- }4 j7 vb Department of Biochemistry, University of Alberta, 4-60 Medical-Sciences Building, Edmonton, Alta., Canada T6G 2S7  p# ^4 ~) z  J/ {7 X/ }& E9 {- a
Received 13 August 2003; accepted 16 September 2003
' F( q3 b+ {0 i. e$ ]! v; NAbstract
4 K' b8 ?1 X6 h! N# cType 1 diabetes is a debilitating condition, affecting millionsworldwide, that is characterized by the autoimmune destruction
* x. w9 W$ ^# c6 mof insulin-producing pancreatic islets of Langerhans. Although exogenous insulin administration has traditionally been the
3 z$ L8 V1 x3 H6 j0 w% c9 Smode of treatment for this disease, recent advancements in the transplantation of donor-derived insulin-producing cells have
# q& C. F8 u8 O0 B) G+ kprovided new hope for a cure. However, in order for islet transplantation to become a widely used technique, an alternative
1 d" a; w6 d7 z! t! Esource of cells must be identified to supplement the limited supply currently available from cadaveric donor organs. Stem9 _+ u7 |8 a& v' I
cells represent a promising solution to this problem, and current research is being aimed at the creation of islet-endocrine
) m" ^- [* S4 Z  H- x3 a5 u1 Atissue from these undifferentiated cells. This review presents a summary of the research to date involving stem cells and cell* p2 ^3 e3 I, ?6 M3 r
replacement therapy for type 1 diabetes. The potential for the differentiation of embryonic stem (ES) cells to islet phenotype
1 {; ^& z  L3 n; C+ sis discussed, as well as the possibility of identifying and exploiting a pancreatic progenitor/stem cell from the adult pancreas.! U8 g/ a: \  X( e
The possibility of creating new islets from adult stem cells derived from other tissues, or directly form other terminally: E; @% H. f% r) s) ?( ?1 ?
differentiated cell types is also addressed. Finally, a model for the isolation and maturation of islets from the neonatal porcine% \4 G+ ~& r# m" w% k; {
pancreas is discussed as evidence for the existence of an islet precursor cell in the pancreas.
  P" }3 k( b  m. u/ q© 2003 Elsevier Ltd. All rights reserved.
* w+ O" W( T; J3 Q5 w. ]Keywords: Stem cells; Type 1 diabetes; Islet transplantation; Differentiation; Xenotransplantation
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