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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。
' k: ~# d6 x- C/ w FThere is continuing disagreement as to whether MSCs can be, r; L- e; a6 k1 T
called stem cells or perhaps adult stem cells. Unfortunately, the, Z% c. \4 B/ y& r% k$ G: }
term stem cell has been embedded in the literature with varying
1 k. v1 N ~( @degrees of rigor. A newly fertilized egg is the cleanest example of
& e2 \$ n2 b R3 X- \/ Ha stem cell that meets the classical criteria: it can divide asymmetrically,* ?, G$ v$ O0 R& [' W/ _
and differentiate into all cellular phenotypes. But, as
& A7 D# Q, v, d0 d" Mhas been repeatedly pointed out, we quickly move down a slippery
U. S6 k) h. d" C' g, B; v( g6 \slope in using the term for similar cells. Embryonic stem
4 {+ _8 ^5 s9 w0 L; Ncells require a slight loosening of the definition, as they rarely differentiate
$ B; ^4 S x: A7 m) einto the trophoblasts of the placenta.18 Hematopoietic
0 n( n; O3 L5 Xstem cells, epithelial stem cells, and neural stem cells further
$ Q) r; x1 R/ d. S/ rstretch the definition, because, with a few dissenting opinions,4 r" B$ b3 ~9 N2 T6 V# Q
they are generally believed to differentiate only into restricted0 B7 i5 n x2 W: B
lineages. MSCs obviously require a similar loosening of the definition; Z! U2 c( \; y: F+ ?" j: A
of stem cells, as the term is applied to the large family of, h1 J8 o+ q2 q" ~0 n. n
nonhematopoietic stem-like cells that have been isolated from- _( w9 K: B3 G) w: r' G- m
most mesenchymal tissues such as bone marrow, fat, and blood# x& b7 E8 F; }: d8 h9 [
vessels. The debate on whether MSCs can be called stem cells in
. B6 ^/ ~2 z2 |- p8 K# `part revolves around the question of whether they can be differentiated& g8 S/ z4 X: X+ L: F6 ~0 U; A( X
into nonmesenchymal cells. Some of the earlier observations# z9 Z7 T" C# C& }' Q: o/ K
on differentiation of the cells were probably flawed because3 B! |; [, l, G- I' k
of technical limitations such as unreliable labels for the cells and. }: ]) G+ a) s2 g; Y8 v7 V7 Q
inadequate experience with potential artifacts.19 But, numerous4 I( o8 t) U# B9 B; t
investigators are continuing to report that MSCs or related cells
# X3 ~5 R ^( k8 Z$ Q" Ifrom bone marrow and other tissues can be differentiated into6 V d i/ a& A0 L- f8 }
epithelial, endothelial, and neural cells.5,20–23 At the same time, the* K. w) H. v( j# g, c) y5 y1 R
definition of a stem cell is further confused with the recognition1 @* v8 ~/ \! e3 Q/ L7 {# O
that the properties of a stem cell depend as much on the niche( z9 V# l' l& `. w- h6 j' O4 g
in which it resides as on the inherent “stemness” of the cell. As
+ m; _9 b4 t% q& Vconcluded in a recent review on hematopoietic stem cells,24 the
) k* V4 V+ F3 t: B8 n. I( Jconcept that stem cells differentiate in a hierarchical manner dictated2 J, E9 s% a1 T8 ^% ` l% N
by the inherent properties of the cell is a “seductive … oversimplification….”
. P6 J6 T3 h# z+ z. |9 GIt ignores the dynamic interaction between' _4 {$ [9 s6 `8 m* X9 b
cellular niches that determine the fates of stem cells. In effect, the! U8 q5 i; }3 k, h: g
emphasis on hierarchical differentiation of hematopoietic stem" |4 N7 T, J Q( g( F" J6 x
cells overlooked the critical role of niches that was clearly demonstrated
& m5 H( B; j5 }, X% \ wby earlier studies in simpler systems, such as oogenesis
! y& \ w" d$ X- x" n6 h5 Xand spermatogenesis
# y m/ k* a* g, ]) pin Drosophila.Of course, the definition of a stem cell is blurred still further
$ w! O% x. d4 Z' V1 H: z, A, S# Dby nuclear transfer experiments and the more recent experiments
! a& e) X1 i5 Vwith induced pluripotent stem cells in which even a transient
* W" y9 a' W( z- ^exposure to the appropriate transcription factors is sufficient to( K2 w( Q1 @( C( r3 y" m" b( P
reprogram the genome to a stem-like state.26 The results suggest; `* N$ v& d% r* T
that differences between a stem cell and a fully differentiated
5 S1 Q. A5 K" n% Q! `9 o5 Wcell are primarily a question of the ease with which external or
' f) \9 ^* k4 b# Z. Zinternal signals can change the microenvironment of the nucleus
0 j0 v" H; v) i& ~sufficiently: U- i6 O- }0 i: _. }7 y8 w
to redirect the phenotype of the cell.
. H1 @6 j( W5 S( m# s! z3 D" `How can we resolve the current confusion concerning the
: Z7 W% Z0 _+ v2 Edefinition of a stem cell? Unfortunately, we cannot yet fully define6 b3 V D; @6 K. \/ x t
the state of any cell in terms of all its transcripts, its epigenetic
+ I! E( w' n/ `$ I$ |4 n) d gstatus, and especially its proteomics (see recent review in ref. 27).
3 ~: d- j! g! mAlso, a static picture in time of a cell is probably not sufficient.
# f- v3 g6 G0 T0 k X6 [" RThe essence of a stem cell is not its status at a given point in time.
* l, g8 X0 D* UIt is the potential for change in an almost Aristotelian sense.: f; G) b0 ^, l8 H' Q3 u7 `' v
Unfortunately, again, we do not have the means of defining the. o; K0 r7 z4 B
potential of a cell in a quantitative manner. The only practical
" |( @2 k0 O) E0 G3 O+ I1 l. bsolution to the current confusion is apparently in trying to convey3 ]. ?- o5 H. x3 @0 V9 L0 R+ h
the context of each type of cell with qualifiers such as hematopoietic' e5 q2 D& _; Q5 ]1 ^
stem cells or adult stem/progenitor cells. |
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发表于 2010-7-6 19:46
发表于 2010-7-6 21:19
