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最近看了篇文献不是太懂,想请教各位:MSCs是干细胞吗?干细胞干性标准与壁龛的关系。- p( r; ~' d& r8 f& Y7 @8 l
There is continuing disagreement as to whether MSCs can be @* X1 f E% Q
called stem cells or perhaps adult stem cells. Unfortunately, the, ]- M. R1 g" U! n* q) M' S
term stem cell has been embedded in the literature with varying
G+ W% z1 `% V2 o6 V( T6 @- idegrees of rigor. A newly fertilized egg is the cleanest example of" s2 B. m6 h) s- n* p0 C
a stem cell that meets the classical criteria: it can divide asymmetrically,' r. q% [2 X" H& t* K" M
and differentiate into all cellular phenotypes. But, as1 H ~4 {9 H7 ]8 v) P% t* u: \
has been repeatedly pointed out, we quickly move down a slippery* K5 f9 F$ P9 B; `' k
slope in using the term for similar cells. Embryonic stem
" Q: A8 y- Q+ b8 fcells require a slight loosening of the definition, as they rarely differentiate
f" I& F7 h- a5 C8 p. s" P+ minto the trophoblasts of the placenta.18 Hematopoietic- j- o6 s$ G8 t$ U; u/ i5 D& X( q
stem cells, epithelial stem cells, and neural stem cells further
, W3 u L9 X2 [% F1 q Ostretch the definition, because, with a few dissenting opinions,6 K4 _5 m. Q6 _
they are generally believed to differentiate only into restricted
& Y, J0 ~5 i# ^0 M7 V2 ~* jlineages. MSCs obviously require a similar loosening of the definition% r% d2 @( r& s5 H! U3 _7 Y
of stem cells, as the term is applied to the large family of+ Z2 m, G/ X: T( W, a! w s# S
nonhematopoietic stem-like cells that have been isolated from2 M- o5 g9 N/ [: s
most mesenchymal tissues such as bone marrow, fat, and blood3 |/ \+ s) o, ? o- `
vessels. The debate on whether MSCs can be called stem cells in2 w& R( y- ^5 U( j# w) R+ N
part revolves around the question of whether they can be differentiated
* s0 z# z4 J4 R+ x* Binto nonmesenchymal cells. Some of the earlier observations- G7 y: d& y7 B! I* u# s
on differentiation of the cells were probably flawed because
. `; G+ t& e6 Oof technical limitations such as unreliable labels for the cells and8 `) v& y$ v4 i( b3 ?* b
inadequate experience with potential artifacts.19 But, numerous" R* R6 p! y4 J) q
investigators are continuing to report that MSCs or related cells, d; [1 n$ z$ R1 y2 T' x
from bone marrow and other tissues can be differentiated into
6 d: _9 T* V6 x- O' ]epithelial, endothelial, and neural cells.5,20–23 At the same time, the
8 Q4 g" G8 |3 N* E0 h7 \0 u+ L; Bdefinition of a stem cell is further confused with the recognition
# _ H( ]. I( K; ^6 Qthat the properties of a stem cell depend as much on the niche, R+ @4 V" Y' g
in which it resides as on the inherent “stemness” of the cell. As: _- ~" Z; i. Y7 ^7 |/ F3 Z
concluded in a recent review on hematopoietic stem cells,24 the
1 E* m% @! c* z' W/ bconcept that stem cells differentiate in a hierarchical manner dictated' M, b# z" F- R0 s7 I+ o
by the inherent properties of the cell is a “seductive … oversimplification….”
; n7 z8 }, B5 u' d8 IIt ignores the dynamic interaction between
6 K6 r3 h J9 S1 h# r! Ncellular niches that determine the fates of stem cells. In effect, the
4 J9 d2 ^4 A9 \6 O# Y0 t5 N3 Demphasis on hierarchical differentiation of hematopoietic stem
! J6 j+ y, Z2 r. A; d+ N" s; Ocells overlooked the critical role of niches that was clearly demonstrated
; A' R2 C5 h1 t- T8 q6 w# Zby earlier studies in simpler systems, such as oogenesis6 w3 I2 u1 x! A' u$ m
and spermatogenesis! N' L1 [, {7 v
in Drosophila.Of course, the definition of a stem cell is blurred still further
6 {! D5 X) z, i) q8 Nby nuclear transfer experiments and the more recent experiments
5 g% n# a" F" j6 \% e/ y. `2 zwith induced pluripotent stem cells in which even a transient% B; [7 [3 x* s+ a2 P; f
exposure to the appropriate transcription factors is sufficient to0 Z) ^& }; g" S1 D; J$ D
reprogram the genome to a stem-like state.26 The results suggest
! Y( o" c1 t9 C( c$ jthat differences between a stem cell and a fully differentiated4 y9 H V7 y2 O$ Z/ `
cell are primarily a question of the ease with which external or) V4 d$ j% n: f. t5 M: e0 V: R8 l
internal signals can change the microenvironment of the nucleus) e! u7 _* p, Z2 j3 x3 p% B0 `
sufficiently3 }% L* @& ^1 y t7 Q
to redirect the phenotype of the cell.
9 S* x }, G, F5 N/ X1 sHow can we resolve the current confusion concerning the
7 B O9 g% B' {7 i- z4 F: ^definition of a stem cell? Unfortunately, we cannot yet fully define! W7 t. _; _; _+ x( z" y
the state of any cell in terms of all its transcripts, its epigenetic" \; C1 b; ?2 X' `; p
status, and especially its proteomics (see recent review in ref. 27).
p; S) v# [( ?) OAlso, a static picture in time of a cell is probably not sufficient.$ i# Y0 x# T, h
The essence of a stem cell is not its status at a given point in time.
" k: k) Q( J5 {It is the potential for change in an almost Aristotelian sense.
# K: S5 U5 w; L' j4 `0 `1 TUnfortunately, again, we do not have the means of defining the# ]/ I: i) D/ N: o& o8 N
potential of a cell in a quantitative manner. The only practical( x0 P. h- W9 F W. ?0 L& D
solution to the current confusion is apparently in trying to convey- p4 J+ p3 Y8 D" Q _) r
the context of each type of cell with qualifiers such as hematopoietic
# X7 W' k. O& h/ l) G0 G$ z a. rstem cells or adult stem/progenitor cells. |
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