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本帖最后由 细胞海洋 于 2010-8-7 20:58 编辑 0 |1 i4 u4 n3 O1 A
# U$ B* N- W" s2010出版的 Methods in Molecular Biology 系列 vol.660
# g# ^) z7 ^0 R8 |, h3 G! W) [- @* o与本站朋友分享。: O* g- C# _5 S* R( q
(请勿外传,以免引起不必要的版权纠纷)) f& u) S2 G( }! b% a! s& n
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以下为该书前言:
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& a+ w$ c4 k8 |8 V- M% QPreface" Q% K, S! ^6 u& g9 U
The field of regenerative medicine is in its infancy state. Enthusiasm for the potential of
9 E9 J* ~2 i" _9 u- S( Zorgan regeneration lies with the potential pluripotency of stem cells to differentiate into# e) z, P4 s, }, C" h
various tissue types. This volume of Methods in Molecular Biology will focus on the use
3 W* N$ i$ [- Eof stem cells for myocardial repair and regeneration. The emphasis of this issue will be to* @. I! n6 P9 q: \/ |
provide basic scientists, translational investigators, and cardiologists a means to evaluate
$ t- r% Q& D0 E1 `2 }7 y9 L- xthe efficacy and safety of stem cells in a standardized fashion for myocardial regeneration.4 Q: I, ~7 B+ h% u
Many different cell types have been considered for myocardial repair. Adult cardiomyocytes+ Y( _# ^ ?; ?4 O
are unable to survive even when transplanted into normal myocardium. The use
* X6 t/ o& g l2 Jof fetal or neonatal cardiomyocytes is not a feasible source of cells due to ethical concerns
9 N; W: N; p: X$ J1 ^, O8 ?and donor availability. Therefore, the use of pluripotent stem cells has become the focus
, G" O4 o6 t4 N2 g, E/ m8 T. ^of a cell source for myocardial repair and regeneration. A variety of stem cell types have7 M9 x, |0 T2 z, q# V* J7 Z: a) n+ Q
been suggested to participate in myocardial repair. This has led the investigators to search
$ j. x8 L& U9 H+ [1 Ifor the “optimal cell type for myocardial repair”. Reliable isolation of the cell source with4 ]# m4 A- {& ^. t: ]
the ability to expand the cell population is a prerequisite. In the first section of this book,
5 z1 q+ E0 x% ]; r) X, L4 Smethods for isolation of commonly used stem cells being investigated for myocardial
/ S4 n( D1 ?! g/ p( tregeneration are presented./ N+ j( a! r7 ~5 ~2 y8 n6 @ A% J
Once a stem cell source has been selected, the stem cell needs to be tested in an appropriate
) j- k' ?8 N) S! ^7 @animal model before being translated into clinical practice. Section 2 discusses both- z, I$ X2 g8 u& _, f6 n. s6 Q3 E" b
rodent and large animal models. The pros and cons of utilizing each of the models are
6 t4 C6 G( U! G8 ^) Y* ndiscussed, as well as obtaining consistent myocardial pathology to test whether the stem& |* ~6 u: r6 k3 i5 _' ]
cells improve function. Techniques used to assess left ventricular function are described for t! w6 F" [3 `( s& I6 X; A
both rodent and large animals, as well as methods to identify stem cells and their effect on
0 a8 D' b# S* zmyocardial repair.% Z6 F# B- V' a0 H" D5 k$ y
Understanding the developmental process of the human heart is paramount to developing$ l z9 b- @; z+ R& B
strategies for myocardial regeneration. Knowledge of the cellular components of
0 D K# Q- J" c8 O* R9 E e& cthe heart and their response to injury is crucial in designing experiments and therapies for, I( M) ~9 u* i( g1 ^' Y1 e# E" I W3 j) K- F
myocardial repair and regeneration. Discrepancies in results of stem cell differentiation
" @& Y! V+ p5 ?into cardiomyocytes and its efficacy are commonly dependent on the interpretation of the
" T& c! o% H$ }- {histological results. Section 3 reviews the histological characteristics of the developing and. C" |# k% _. \+ Y3 v8 O- I2 n; m5 k
normal myocardium and provides the histological chronology of the heart following a
. A# S* F% P4 i1 w' ?9 B4 W% Emyocardial infarction. Strategies for myocardial regeneration also include means to develop
4 Z* m8 o7 y) j0 [a functional vascular system. It is important to discriminate between increases in capillary
$ Q/ r2 m$ I: p, j) r jdensity that commonly do not increase blood flow and arteriogenesis that will lead to an% O: W5 B, R- j3 m" t% W8 }
increase in blood flow. A detailed analysis of angiogenesis and methods to delineate the8 N% R$ \1 j! b9 Z. [
types of vasculature produced by stem cells are also discussed in section 3.' A: ~, }: `6 N9 o" \6 e
Once a stem cell is transplanted into the myocardium, it is of great importance to
5 _7 E' q" F2 [0 D* _determine its fate and to assure safety. MRI and molecular imaging enable the identification% h& j$ K; H7 b5 B: ^
and tracking of transplanted stem cells. The use of superparamagnetic iron oxides to
: d) _; ?" m6 I8 z9 Olabel stem cells has enabled investigators to utilize MRI to assess the injection of stem cells- K7 N5 Q; a: y) \- w- M% A5 c6 r1 }
into the injured area and its effect on both segmental and global left ventricular function
3 u7 j+ d& H4 kand myocardial perfusion. Transfection of stem cells with a reporter gene allows the d J7 U% L1 j6 B* `
reporter probe to produce a signal detectable by commonly used imaging modalities.
/ I7 V: {1 s; mMolecular genetic imaging is confined to viable stem cells and the population of stem cells! x* Z! W& @, U
transfected, thus allowing for longitudinal tracking of stem cells. Molecular imaging has- ]) S0 a8 u+ Q8 a
been particularly useful in following embryonic stem cells and their propensity to form4 W- H/ ?! i4 I3 x2 H2 ^, `5 c
teratomas. Recently, the beneficial effects of autologous stem cell therapy have been attributed$ H: a ^! b8 `5 q8 T5 n
to paracrine effects. The use of a genetic fate-mapping approach is reviewed in section
$ ?( z0 U2 V2 L! V) b4 to study adult cardiomyocyte replenishment following an injury. The use of the
' |" u$ p5 L/ g- ptools in section 4 will allow investigators to address challenges of stem cell therapy such as
3 D; j/ q+ m% v9 bstem cell retention, engraftment, and safety, and investigate the mechanisms of stem cell' C& `# h7 c/ A- H# q/ u9 G
therapy.
% d# }6 q! G) c4 T! NThe emphasis of myocardial regeneration has focused on improvements of left ventricular0 D* ^7 C. f3 U' g. p$ V
function; however, an electrically integrated transplanted stem cell with its surrounding- s- S T0 \" t p5 ?# e$ T
environment is necessary to mitigate abnormal arrhythmias and optimize
9 G8 U6 f |6 I5 _+ g' X# j5 w o/ Belectromechanical performance. Both in vitro assessment of cellular electrophysiological5 X& s. i/ y; J6 p9 o# [
properties and cell-to-cell communication can be accomplished with multielectrode array
' r+ i2 x, x$ ]recordings and optical mapping. These studies can be complemented with either ex vivo
) s1 w% N$ D: F( T. r# Foptical mapping or in vivo electrophysiology studies. These methods are presented in7 x9 b' R7 \2 }4 v9 f+ F
section 5.- V5 ?! p6 K& m7 j1 d) f4 A
Tissue engineering techniques have been used to enhance cell retention and create the# ^( ?, j# G }8 R! x9 O) O5 \
microenvironment to allow for stem cell survival. More recently, the extracellular matrix- N3 x/ H. I3 N+ ^' H! J1 `
or functional groups derived from extracellular matrix proteins have been shown to influence) u. g4 k. P) `& B% E
stem cell binding, the production of growth factors by the stem cell, and stem cell
7 e1 l# z% B) r2 Ndifferentiation. In the final section of this volume, a strategy for investigating the effects( Z0 s% \) G7 }( v8 G( U9 u& ^9 R
of the extracellular matrix on stem cell renewal and differentiation is presented.
$ N7 x+ Q3 m* s& ?The methods presented in this volume of Methods in Molecular Biology attempt to
$ d+ r' r$ z% C$ ?- g$ y$ ^# i' Whighlight techniques and strategies to be utilized in investigating the many challenges that7 ]* S# u: A6 \) H
need to be addressed before stem cell therapy can become a mainstream therapy for myocardial" j2 M f2 M8 V+ K& n. u/ z8 h
regeneration., L5 X Q: \! p g. B) h
4 h" @( e4 y* |" G
San Francisco, CA 0 L, r# j0 |% O. O* m" A$ p( W
Randall J. Lee! R- u" y& a. j$ H
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