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本帖最后由 细胞海洋 于 2010-1-16 07:24 编辑 Q& _! l) v( D0 _' x$ R( I e' {
" j+ X. P; p' B: k, A# FABSTRACT
8 N" ]' g) `6 W0 ]$ d6 aVarious attempts have been made to develop stem cell-& f9 o$ h7 F `/ `5 G8 X
based therapy to alleviate type I diabetes using animal
- R5 \6 g0 T2 @& [1 B6 _- wmodels. However, it has been a question whether human S7 x) r" F6 |' W, f
insulin produced from explanted cells is solely responsible
. o1 }( D! J4 f: H$ ^. l$ vfor the normoglycemia of diabetic animals. In this study,2 f9 F3 `: X U% m# G
we isolated neural crest-like stem cells from the human eye-
4 N2 _: Z3 H, x( u# ~2 alid fat and examined their therapeutic potentials for
# O; N( J; [7 y" Ediabetes. The human eyelid adipose-derived stem cells# G: K/ ~0 o2 T
(HEACs) displayed characteristics of neural crest cells.
" s- ^5 l' u, S* T9 Y; `Using a two-step culture condition combined with nicotina- B* ^$ x. g8 B
mide, activin, and/or GLP-1, we differentiated HEACs into1 C1 F3 z' C4 Y& h& l2 S
insulin-secreting cells and examined in vivo effects of differ-
! j3 N* x' T5 X- O" Ventiated cells by transplantation experiments. Following dif-# [6 }9 h; I3 E9 x. {" `
ferentiation in vitro, HEACs released insulin and c-peptide
$ |& ~2 W' ^6 c# J5 R/ g# qin a glucose-dependent manner. Upon their transplantation; q) Z. r, u: w8 R& E1 ?7 R0 V+ M
under kidney capsules of streptozotocin-treated immuno-
' T1 z- h2 `- a; C" _3 ncompetent mice, we observed normalization of hyperglyce-+ E+ E4 c+ p- ~6 z4 q
mia in 10 of 20 recipient mice until sacrifice after 2 months.
0 ^" a W) u3 E. E @1 t! ]% u; ~Only the human, but not the mouse, insulin and c-peptide* O1 W1 g- }! M
were detected in the blood of recipient mice. Removal of the1 Q. M* q( J& v
kidneys transplanted with HEACs resulted in a sharp
0 w3 H- ?3 I r7 n* D! Hincrease of blood glucose level. Removed kidney tissues
Q( H/ l! q! Y$ j) [3 l6 X% C# }: sshowed distinct expression of various human genes$ q6 @. h' D) y, c+ P( X& F
including insulin, and colocalization of the human insulin2 i6 j7 I4 ?$ B J" O* c' \8 G
and the human nuclear protein in many cells. However,
0 S, Y4 [' q* R3 z% Z4 T" R% mthey showed diminished or null expression of some immune-& H, K* N+ V2 C( r q& D1 @4 U
related genes. In conclusion, human insulin alone produced8 A' W' I* v5 d5 D* B5 k
from eyelid-derived stem cells following differentiation into
6 z; N9 p+ ~9 v' L' _insulin-secreting cells and transplantation could normalize
: e+ }% k' y3 N3 s; P* gtype I diabetes in mice. STEM CELLS 2009;27:1999–2008) z1 {, O6 \- u$ U
# S$ ]* u% K& H& _3 O# X
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发表于 2010-1-16 02:12
