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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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ABSTRACT
, q& r* `& x- g' U$ V$ MVarious attempts have been made to develop stem cell-
9 n ^) L4 p1 |based therapy to alleviate type I diabetes using animal
2 P( a. y0 v; J6 d. ]+ P( Ymodels. However, it has been a question whether human
# S5 H" \; F9 i. s7 Z; r! H! J" ainsulin produced from explanted cells is solely responsible
( B+ l" I0 ?# ifor the normoglycemia of diabetic animals. In this study,! E4 s% ?3 @8 U- w1 {3 b2 F
we isolated neural crest-like stem cells from the human eye-9 ~% g6 p* F( ]
lid fat and examined their therapeutic potentials for/ v: w5 W; o. ^# y( H
diabetes. The human eyelid adipose-derived stem cells
! K2 H r, o5 \$ k B: @(HEACs) displayed characteristics of neural crest cells.1 p# O* \1 A) I+ O
Using a two-step culture condition combined with nicotina-: C4 S( D0 V1 Z1 i2 H, b! n' Z8 G
mide, activin, and/or GLP-1, we differentiated HEACs into$ }( ~7 v% I- |
insulin-secreting cells and examined in vivo effects of differ-9 h3 _4 ^9 l9 J! C# H
entiated cells by transplantation experiments. Following dif-
3 G: ^, i- _1 o+ q0 Cferentiation in vitro, HEACs released insulin and c-peptide
! b9 b0 j7 H/ w; M, S$ r* iin a glucose-dependent manner. Upon their transplantation2 J E9 h5 L, B3 S
under kidney capsules of streptozotocin-treated immuno-
0 q5 G( N, U" Z6 ~: Q7 C, Y! t vcompetent mice, we observed normalization of hyperglyce-
( D; G8 _6 C* T, M+ I) Mmia in 10 of 20 recipient mice until sacrifice after 2 months.' Z" `2 @( V" v. q; E
Only the human, but not the mouse, insulin and c-peptide
) ^2 B _: `* J# e1 owere detected in the blood of recipient mice. Removal of the
6 z2 D" d [& d# [4 `5 Hkidneys transplanted with HEACs resulted in a sharp
! s5 k" M$ S; ~4 C+ R6 ~increase of blood glucose level. Removed kidney tissues
9 R+ w1 K8 O7 `- ashowed distinct expression of various human genes% q/ ~+ G4 e3 T4 K2 u+ J
including insulin, and colocalization of the human insulin
2 i% E, b4 \3 o, Y1 e5 J+ rand the human nuclear protein in many cells. However,
: S: r7 x0 M; Y2 c# `) tthey showed diminished or null expression of some immune-
: t- t* J& F5 U* R. Srelated genes. In conclusion, human insulin alone produced
5 h8 x* N1 ]3 h& [3 \6 R- u2 yfrom eyelid-derived stem cells following differentiation into
- S! A; z: j/ Y r, j% p$ f6 Binsulin-secreting cells and transplantation could normalize
3 u/ e3 `; n. ztype I diabetes in mice. STEM CELLS 2009;27:1999–2008/ }- Q( j- [; K" w7 e& S, L
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发表于 2010-1-16 02:12
