PDF电子书：Insulin-Secreting Cells from Human Eyelid-Derived Stem Cells

decloud2009

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& \' D1 `* s; U* u3 F" yABSTRACT2 h+ D  T4 B* @& O. R, \
Various attempts have been made to develop stem cell-. ]3 T4 X7 A' }. |
based therapy to alleviate type I diabetes using animal6 W0 r8 ]; I+ z+ ^! ]: ^
models. However, it has been a question whether human
5 ^; F- w: @& k2 O; ^insulin produced from explanted cells is solely responsible) Q7 M5 p$ B* ?& i4 [) w* m
for the normoglycemia of diabetic animals. In this study,
% J8 g! p; F, t% \  m; c- B7 T4 ~we isolated neural crest-like stem cells from the human eye-" \7 r9 v& d+ j
lid fat and examined their therapeutic potentials for
( K2 ^+ i* f. k- Sdiabetes. The human eyelid adipose-derived stem cells/ e& q1 C, D  Z1 }" K% s9 s( _; t
(HEACs) displayed characteristics of neural crest cells.
6 B- P5 N6 n- I6 hUsing a two-step culture condition combined with nicotina-
$ m9 w8 j* f+ A# Omide, activin, and/or GLP-1, we differentiated HEACs into5 [- e& x$ q2 w6 r- {( g" J! M& h
insulin-secreting cells and examined in vivo effects of differ-
2 c- \& L, P7 [* ?entiated cells by transplantation experiments. Following dif-2 I( |0 v9 v( H0 N, N
ferentiation in vitro, HEACs released insulin and c-peptide
8 T& Z5 N9 r. m- L) win a glucose-dependent manner. Upon their transplantation
3 e  p: q+ s6 [3 _under kidney capsules of streptozotocin-treated immuno-4 |. J0 y0 Q6 _) ^- w* |
competent mice, we observed normalization of hyperglyce-5 R! h. B: x$ s( f2 `% l
mia in 10 of 20 recipient mice until sacrifice after 2 months.
0 v8 Z2 }6 \" HOnly the human, but not the mouse, insulin and c-peptide5 X' S8 F8 n  ^6 y
were detected in the blood of recipient mice. Removal of the
  L, G7 Z2 M+ m7 d0 t8 d! Wkidneys transplanted with HEACs resulted in a sharp4 l% P# L) }4 b; l( ]' g
increase of blood glucose level. Removed kidney tissues
/ Q8 q5 J0 W. @# V1 n1 B+ d3 E2 Ashowed distinct expression of various human genes- [& n1 C$ W& u- k7 E
including insulin, and colocalization of the human insulin* Y9 _# U% v1 B" m2 E
and the human nuclear protein in many cells. However,. B0 W( d& O+ e& ~, f* v4 o% c
they showed diminished or null expression of some immune-
7 ^3 @& J6 D$ c, \* b+ r8 Irelated genes. In conclusion, human insulin alone produced; m5 H; n; e4 N4 A$ Q. _4 y3 P
from eyelid-derived stem cells following differentiation into
) X2 A# |% D2 x2 {insulin-secreting cells and transplantation could normalize; J0 Y8 Z) S# [  q# W: J2 E; p
type I diabetes in mice. STEM CELLS 2009;27:1999–2008
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decloud2009

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