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本帖最后由 细胞海洋 于 2010-1-16 07:24 编辑 + P/ k) }8 _. \& a. p
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ABSTRACT- ^# f5 z/ E/ }
Various attempts have been made to develop stem cell-/ v8 l6 j9 f6 z. R( F1 O
based therapy to alleviate type I diabetes using animal- |& i+ N! A. Q; ~5 w
models. However, it has been a question whether human
# j! u2 U) L/ ]0 e Iinsulin produced from explanted cells is solely responsible
0 l5 P5 s5 N2 t: ufor the normoglycemia of diabetic animals. In this study,
+ C' d/ y9 n {* B1 }we isolated neural crest-like stem cells from the human eye-6 K9 v, ~) d* L* y
lid fat and examined their therapeutic potentials for1 k. V: b$ k- W1 V: ^0 n
diabetes. The human eyelid adipose-derived stem cells, X% Y T# a, {! Y. k( U
(HEACs) displayed characteristics of neural crest cells.
7 c% P: G j& p" aUsing a two-step culture condition combined with nicotina-; ~( W" f# A T
mide, activin, and/or GLP-1, we differentiated HEACs into
; C4 U/ e; \( T# Finsulin-secreting cells and examined in vivo effects of differ- }4 Y6 i) \8 Q% T* [4 }
entiated cells by transplantation experiments. Following dif-" y2 \. r# K# E4 |0 }
ferentiation in vitro, HEACs released insulin and c-peptide
5 s; M% v0 z; Z: T! x% V |' O! Hin a glucose-dependent manner. Upon their transplantation
, o" ]0 Z' E# _0 g! Punder kidney capsules of streptozotocin-treated immuno-3 X H8 s n' R. F! f# m% q' f* D7 |
competent mice, we observed normalization of hyperglyce-( p/ _/ f9 \, X6 \2 ~: [
mia in 10 of 20 recipient mice until sacrifice after 2 months.
" D& O0 _$ j9 MOnly the human, but not the mouse, insulin and c-peptide! b3 Y4 ?, h9 P9 X
were detected in the blood of recipient mice. Removal of the
1 x4 R- \0 D0 Xkidneys transplanted with HEACs resulted in a sharp
" u7 A2 ]* H9 V# Nincrease of blood glucose level. Removed kidney tissues
% Z: w6 @* I( G- v1 E3 Bshowed distinct expression of various human genes' I5 D+ k7 \1 Z& y. L+ e
including insulin, and colocalization of the human insulin/ g9 q& F I" C% X7 f& z0 y
and the human nuclear protein in many cells. However,
6 v% n, H( {) ~they showed diminished or null expression of some immune-; F" J G9 w3 F$ d S
related genes. In conclusion, human insulin alone produced
' @9 l# o! c: @ M8 q. Q& Jfrom eyelid-derived stem cells following differentiation into* h/ c9 J2 K! |0 ^& N
insulin-secreting cells and transplantation could normalize: W: L. |( e/ V# C- r) b
type I diabetes in mice. STEM CELLS 2009;27:1999–2008
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发表于 2010-1-16 02:12
