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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。% o" v1 M/ }0 ` g
There is continuing disagreement as to whether MSCs can be
+ q* F+ W9 o b, J5 I" Kcalled stem cells or perhaps adult stem cells. Unfortunately, the
6 o5 c) ?) d! M& S" S. n$ x6 Oterm stem cell has been embedded in the literature with varying
; `% S: ?, }# I5 V7 R. r4 e/ ~degrees of rigor. A newly fertilized egg is the cleanest example of
# U0 b( j/ n# F; Va stem cell that meets the classical criteria: it can divide asymmetrically,7 c& y/ W5 p* ?9 x7 F( g
and differentiate into all cellular phenotypes. But, as4 O7 r1 h$ m Z8 U) p2 a' D
has been repeatedly pointed out, we quickly move down a slippery% X% [9 h6 `' f
slope in using the term for similar cells. Embryonic stem
0 e. T% W3 k+ T: S7 o1 Xcells require a slight loosening of the definition, as they rarely differentiate. j% O w! N/ k3 N8 b! q
into the trophoblasts of the placenta.18 Hematopoietic1 ?" w3 u: @2 F5 O' w* o
stem cells, epithelial stem cells, and neural stem cells further/ D- A: |# [ d+ o! j3 g4 I
stretch the definition, because, with a few dissenting opinions, e+ \7 J/ @' T5 @7 H: @! Y
they are generally believed to differentiate only into restricted+ s$ o4 X- H0 H0 N- U! q9 I
lineages. MSCs obviously require a similar loosening of the definition
6 h0 O# p" j; n" j) Cof stem cells, as the term is applied to the large family of
4 o/ H; }% _( L$ H+ }nonhematopoietic stem-like cells that have been isolated from: }; b2 \% a# b1 Q' T
most mesenchymal tissues such as bone marrow, fat, and blood
, a7 ~ u4 X) Fvessels. The debate on whether MSCs can be called stem cells in
. o7 r5 u! G7 x- X" C( Epart revolves around the question of whether they can be differentiated
1 H) y: r, M9 h7 Ointo nonmesenchymal cells. Some of the earlier observations
$ I1 q$ Q3 _- P. hon differentiation of the cells were probably flawed because
+ F6 |, C* ^! _' S7 uof technical limitations such as unreliable labels for the cells and
6 ]$ h" `" }4 [& B1 Q; U! `inadequate experience with potential artifacts.19 But, numerous
+ u3 W2 Z( R" Q2 }1 U6 J- B! Xinvestigators are continuing to report that MSCs or related cells
; w i8 S4 s. `5 R# V5 Hfrom bone marrow and other tissues can be differentiated into4 J. U: H6 @( `; |) n5 N- n
epithelial, endothelial, and neural cells.5,20–23 At the same time, the- s3 v ?# _( S. ]2 j" w4 F9 W: X
definition of a stem cell is further confused with the recognition) N- k- Q0 p6 m8 K6 v$ A8 X0 q5 k
that the properties of a stem cell depend as much on the niche7 M' o2 j8 m: w' u
in which it resides as on the inherent “stemness” of the cell. As- M/ ~2 `% W# ]7 k) Z% W
concluded in a recent review on hematopoietic stem cells,24 the( z! f- i# Y& `9 X7 `9 W
concept that stem cells differentiate in a hierarchical manner dictated9 D7 b: D& l$ F" v8 j
by the inherent properties of the cell is a “seductive … oversimplification….”9 f* V8 J4 j7 v; T- e a
It ignores the dynamic interaction between9 j: r3 ^$ k5 J' e% n' V) |
cellular niches that determine the fates of stem cells. In effect, the$ K) v7 |- `9 G; h9 M
emphasis on hierarchical differentiation of hematopoietic stem
8 t% X1 K8 _ T0 Y% ^3 y% vcells overlooked the critical role of niches that was clearly demonstrated% W9 @) d% b; `, i% w- t; U) h
by earlier studies in simpler systems, such as oogenesis
8 k( l, I2 X7 X3 W U! i8 f: Band spermatogenesis; V* T9 t2 x: e" Y7 w9 t8 T
in Drosophila.Of course, the definition of a stem cell is blurred still further
1 T" u7 H2 x8 r O& U* Yby nuclear transfer experiments and the more recent experiments0 h$ Y# V8 {8 V! e2 ?: N' d( O Y
with induced pluripotent stem cells in which even a transient
. t4 I' }* h' X. }1 p" Bexposure to the appropriate transcription factors is sufficient to9 A: c6 L E2 ^
reprogram the genome to a stem-like state.26 The results suggest
$ G0 ~ |4 z0 h! w5 i8 I8 xthat differences between a stem cell and a fully differentiated+ m- p4 w7 Y# n0 U2 _" W
cell are primarily a question of the ease with which external or
: z* @* k( [3 A- t$ _, minternal signals can change the microenvironment of the nucleus# A+ Z6 b* f# H6 [4 |
sufficiently
1 ^! X4 K7 V6 W$ R/ N+ [' `( pto redirect the phenotype of the cell.
- F) p" Y& h& SHow can we resolve the current confusion concerning the
9 Y' ^/ o' Q6 L6 u# Rdefinition of a stem cell? Unfortunately, we cannot yet fully define* j( R4 t& v% j) s6 q9 z W
the state of any cell in terms of all its transcripts, its epigenetic
( E0 Y- ~" ? c( Qstatus, and especially its proteomics (see recent review in ref. 27)./ M5 C( Y( r$ S* H! o
Also, a static picture in time of a cell is probably not sufficient.
- @/ b( ~ W: J) u' X- jThe essence of a stem cell is not its status at a given point in time.
& v9 H( v. O+ b# kIt is the potential for change in an almost Aristotelian sense.
- @, `& n* }+ g h0 l) d( t% }Unfortunately, again, we do not have the means of defining the
! b/ }7 T( a3 D9 ], L5 b' tpotential of a cell in a quantitative manner. The only practical- @8 ^( r5 O+ j' @) F0 A
solution to the current confusion is apparently in trying to convey
/ r, D+ A& w* Y3 Rthe context of each type of cell with qualifiers such as hematopoietic
$ j& q6 O( C/ [5 rstem 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
