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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。
t$ Y: F3 s( U: IThere is continuing disagreement as to whether MSCs can be
( R! J0 Z. G4 V1 G9 |* Ecalled stem cells or perhaps adult stem cells. Unfortunately, the
; G: `% v' @2 d _$ Pterm stem cell has been embedded in the literature with varying2 Y: m8 x5 f$ a. G9 _, v: g
degrees of rigor. A newly fertilized egg is the cleanest example of; N0 l. g! c4 |% q
a stem cell that meets the classical criteria: it can divide asymmetrically,3 d7 F0 P2 A3 O8 S) ], C( o
and differentiate into all cellular phenotypes. But, as
$ g2 H: h8 R# X5 R" lhas been repeatedly pointed out, we quickly move down a slippery
# m9 H& z9 f4 i( n, }; Kslope in using the term for similar cells. Embryonic stem% E! E' }- R) |" r
cells require a slight loosening of the definition, as they rarely differentiate
8 e; [5 Q& K7 }) Winto the trophoblasts of the placenta.18 Hematopoietic
/ y0 d& A$ V0 c$ d& n4 o: z; I: wstem cells, epithelial stem cells, and neural stem cells further
" Z5 z- U, j7 f5 Qstretch the definition, because, with a few dissenting opinions,% }7 h' d* e7 _ c5 X5 s
they are generally believed to differentiate only into restricted/ H; R# o; t$ L3 N! v
lineages. MSCs obviously require a similar loosening of the definition
+ {. D) e5 g. O& [ P/ sof stem cells, as the term is applied to the large family of
# ]0 y, T y' M! i1 s8 p8 B+ p+ k, bnonhematopoietic stem-like cells that have been isolated from
9 A' f& T$ a: ~+ J) @+ P$ U7 Imost mesenchymal tissues such as bone marrow, fat, and blood
$ i {; K, v0 b( K, Z3 m2 Jvessels. The debate on whether MSCs can be called stem cells in' |8 N! F- b) g7 S
part revolves around the question of whether they can be differentiated
2 g7 j% f: n: x, v) i2 }) V0 n' Tinto nonmesenchymal cells. Some of the earlier observations$ `/ W3 `6 `/ v5 L4 I
on differentiation of the cells were probably flawed because
9 b( k9 h! C- {1 P0 y" \of technical limitations such as unreliable labels for the cells and0 S1 k$ i+ r$ A+ g+ \; X6 B
inadequate experience with potential artifacts.19 But, numerous
. Y8 J2 I( x0 H; Binvestigators are continuing to report that MSCs or related cells
5 ]* Y: J' H% r8 W- ]8 u7 H1 Gfrom bone marrow and other tissues can be differentiated into
9 }/ g# w% E( I$ X) H) {9 fepithelial, endothelial, and neural cells.5,20–23 At the same time, the l( W' [- i, j0 I4 d
definition of a stem cell is further confused with the recognition+ ]" ~! j6 H# e1 M! G" H- e
that the properties of a stem cell depend as much on the niche
( q0 |- z! A# {" Gin which it resides as on the inherent “stemness” of the cell. As
% @9 _1 E( W6 ]4 `* jconcluded in a recent review on hematopoietic stem cells,24 the/ L: o& z4 e3 E- Q5 Y
concept that stem cells differentiate in a hierarchical manner dictated
0 F7 Z. I5 t2 F9 ^0 \; i$ mby the inherent properties of the cell is a “seductive … oversimplification….”- i8 K# O- B, `( S3 u
It ignores the dynamic interaction between, C" a9 {' C6 K! \
cellular niches that determine the fates of stem cells. In effect, the
" Z1 k$ ^+ f* Y: o& u& h' qemphasis on hierarchical differentiation of hematopoietic stem4 U4 b0 T3 k `, {: U& C& k
cells overlooked the critical role of niches that was clearly demonstrated
/ |. Y; m' ?; H( e$ G* Tby earlier studies in simpler systems, such as oogenesis. A/ G3 C% e. Q: r% l( o+ I. j
and spermatogenesis" M" d, c1 I. \# t: g& u
in Drosophila.Of course, the definition of a stem cell is blurred still further8 b% ?' [" H _: u5 S: X) m( U
by nuclear transfer experiments and the more recent experiments I( ^6 j8 b8 ?5 b1 V% O% C
with induced pluripotent stem cells in which even a transient
4 A1 z% S& I' w8 K; @4 Iexposure to the appropriate transcription factors is sufficient to
0 a$ S3 V n2 B( O" qreprogram the genome to a stem-like state.26 The results suggest
' P* @4 v2 Y4 ithat differences between a stem cell and a fully differentiated* K; ], [1 L5 K' d% V
cell are primarily a question of the ease with which external or
& c# F, @# j3 K8 tinternal signals can change the microenvironment of the nucleus
8 O v; y* e! m% r8 S, Usufficiently3 o6 ?; D3 [2 F& o5 `
to redirect the phenotype of the cell.
5 s+ l4 g" }( u* @2 FHow can we resolve the current confusion concerning the' x( _$ j+ U' `4 e, G, N$ _
definition of a stem cell? Unfortunately, we cannot yet fully define; M6 x9 }- x4 X+ S" S
the state of any cell in terms of all its transcripts, its epigenetic
6 D' q3 e$ b! a) F. zstatus, and especially its proteomics (see recent review in ref. 27).
% N* g, Q9 p; A2 s$ eAlso, a static picture in time of a cell is probably not sufficient.3 ~/ w5 t$ l+ @* |& s1 N
The essence of a stem cell is not its status at a given point in time.: q4 V B9 u/ \8 t0 e9 u# ~
It is the potential for change in an almost Aristotelian sense.
1 c: o3 s; b2 H z% ~' _9 SUnfortunately, again, we do not have the means of defining the
1 w7 g3 Z; U4 H, c9 L1 Upotential of a cell in a quantitative manner. The only practical
8 u$ Y' o& `9 [& [8 ?6 W, `2 ^2 ]solution to the current confusion is apparently in trying to convey
- X+ Z: [# J5 @% U: S* B+ athe context of each type of cell with qualifiers such as hematopoietic
1 r" b; w& M% {5 l. kstem cells or adult stem/progenitor cells. |
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发表于 2010-7-6 19:46
发表于 2010-7-8 00:09
