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本帖最后由 细胞海洋 于 2010-1-16 07:24 编辑
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* {+ {, ?4 }- iABSTRACT/ y- P* Q6 Y1 p. l) A3 m
Various attempts have been made to develop stem cell-( r* Z. b) ^3 J, H9 }/ x& v# f
based therapy to alleviate type I diabetes using animal
( ?' i; r$ ?; F+ J. w1 wmodels. However, it has been a question whether human
' s |( _6 {% z6 Rinsulin produced from explanted cells is solely responsible
$ {; O) J; K3 @1 ofor the normoglycemia of diabetic animals. In this study,
1 J; K2 }; \9 @we isolated neural crest-like stem cells from the human eye-! @$ k+ j6 e9 p9 p X( [
lid fat and examined their therapeutic potentials for, @1 u5 O, i1 A9 K$ Y- i
diabetes. The human eyelid adipose-derived stem cells
4 ~) N* p, k" ](HEACs) displayed characteristics of neural crest cells.9 T/ Y( @9 m+ g$ _% O3 m
Using a two-step culture condition combined with nicotina-! R8 s9 s3 S- D$ S/ _
mide, activin, and/or GLP-1, we differentiated HEACs into
9 Q# D/ c2 U8 b) Y! iinsulin-secreting cells and examined in vivo effects of differ-2 {. h0 q8 t" m- |
entiated cells by transplantation experiments. Following dif-$ q% I$ H( N3 _, R2 ^, d
ferentiation in vitro, HEACs released insulin and c-peptide# s% ?, |& d7 ^
in a glucose-dependent manner. Upon their transplantation
8 m. t* w& Z! X6 D8 T0 Ounder kidney capsules of streptozotocin-treated immuno-- R Q# Z# J+ }9 H) i6 A6 T
competent mice, we observed normalization of hyperglyce-( l# |8 j5 H- m# u: T
mia in 10 of 20 recipient mice until sacrifice after 2 months.8 P- x* B# e3 }! V* |2 x
Only the human, but not the mouse, insulin and c-peptide
! D1 x5 I6 c: m& ~; j# _were detected in the blood of recipient mice. Removal of the
8 u+ |% R* X9 t0 H7 C8 d# _( |kidneys transplanted with HEACs resulted in a sharp
6 w: x7 T" S) [) L; u' S) Hincrease of blood glucose level. Removed kidney tissues
! [9 J7 }: K+ M+ m& C) _) xshowed distinct expression of various human genes
% n" u( p& w0 N' Sincluding insulin, and colocalization of the human insulin5 g( T, e) A) T4 k; w# b
and the human nuclear protein in many cells. However,/ y7 {9 D$ v+ X! B7 e
they showed diminished or null expression of some immune-
/ q$ l# H6 J4 b6 L3 Zrelated genes. In conclusion, human insulin alone produced
2 z0 ]+ \5 j9 b+ Afrom eyelid-derived stem cells following differentiation into
6 {$ s0 o$ H) T, minsulin-secreting cells and transplantation could normalize
9 d& k" ?: W0 b6 Gtype I diabetes in mice. STEM CELLS 2009;27:1999–2008' F* l: p) h& R0 Q/ L. U' f
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发表于 2010-1-16 02:12
