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) P' E/ {5 E, rSecretion of immunoregulatory cytokines by mesenchymal stem cells
: F6 }1 S% a/ j! ?Dobroslav Kyurkchiev, Ivan Bochev, Ekaterina Ivanova-Todorova, Milena Mourdjeva, Tsvetelina Oreshkova, Kalina Belemezova, Stanimir Kyurkchiev，Dobroslav Kyurkchiev, Ekaterina Ivanova-Todorova, University Hospital “St. Ivan Rilski”, Department of Clinical Laboratory and Clinical Immunology, Medical University of Sofa, 1431 Sofa, Bulgaria( }) s3 m/ y# v L: P$ W
Ivan Bochev, Ob/Gyn Hospital “Dr Shterev”, 1330 Sofa, Bul-
. f: M9 n2 K5 w1 [/ [' }garia
; d1 I5 K' X9 IMilena Mourdjeva, Tsvetelina Oreshkova, Laboratory of Mo-, r! n) Y! M' t k9 a( A: b# i
lecular Immunology, Institute of Biology and Immunology of Re-
; \ h/ B: B- u: T1 x, g) nproduction, Bulgarian Academy of Sciences, 1113 Sofa, Bulgaria
9 q. g* W/ l, G6 \Kalina Belemezova, Stanimir Kyurkchiev, Tissue Bank “BulGen”, 1330 Sofa, Bulgaria! r5 t* Y2 ~5 @0 ?: Q, P( R) G, f
Author contributions: All the authors contributed to the research and in the preparation of the paper; Kyurkchiev D was also responsible for designing and editing the review.
7 d4 u: T/ a% k% L# `' C+ ZCorrespondence to: Dobroslav Kyurkchiev, MD, PhD, As-; n0 W- E/ ~6 g- ^/ W/ p' u6 [7 Y
sociate Professor, University Hospital “St. Ivan Rilski, Depart-
1 L% O! e( J& S. s/ n% _+ ?ment of Clinical Laboratory and Clinical Immunology, Medical & i, a/ g+ @! q2 V& w2 p( _
University of Sofa, 15 “Acad. Ivan Geshov” Str., 1431 Sofa, ' m/ w2 h' R- u0 N! W+ ^
Bulgaria. dsk666@gmail.com
3 ^" m% t: {# P q0 qTelephone: +359-2-85249579 Z% w! K2 h: u( B, R3 }) \
Received: July 14, 2014 Revised: August 20, 2014
+ ?# n# e$ H' a( xAccepted: September 4, 2014
: B, v7 ~/ L" }' ZPublished online: November 26, 2014( u# A0 q- A4 C l1 c% U% x, _
Abstract/ J. f: P& Y2 J7 _+ d, v
According to the minimal criteria of the International ! B" l: T1 F; ^- c
Society of Cellular Therapy, mesenchymal stem cells
! U' m# Z0 j$ J(MSCs) are a population of undifferentiated cells de-! Q: N3 c! r3 V& e- [+ ?
fned by their ability to adhere to plastic surfaces when ; ?2 x- Q: O3 f) V1 m# h/ T
cultured under standard conditions, express a certain $ e5 r: M6 z" k! {& u1 t
panel of phenotypic markers and can differentiate into : K9 C+ f0 @) Q5 C2 H7 @
osteogenic, chondrogenic and adipogenic lineages ; q% L* f5 ]$ Z: e% V
when cultured in specific inducing media. In parallel 3 W! V" p2 F6 q3 U
with their major role as undifferentiated cell reserves, % C: Y5 a9 B) q% |+ e. A
MSCs have immunomodulatory functions which are
6 x' b% t% e# L+ v: B1 P$ qexerted by direct cell-to-cell contacts, secretion of cy-- W, l4 l. S: v$ g$ Z- Y
tokines and/or by a combination of both mechanisms. ' `: J" `, B: X$ j
There are no convincing data about a principal differ-4 _: Z; ~ ~8 {( {, M' e
ence in the profle of cytokines secreted by MSCs isolat-
. D e" ^: k+ e7 Ted from different tissue sources, although some papers
& i1 v/ x8 B4 M" B# K( Sreport some quantitative but not qualitative differences + c0 K3 P0 U$ |& C/ Z7 M
in cytokine secretion. The present review focuses on w0 j- Q) d( J; f
the basic cytokines secreted by MSCs as described in
, G% N8 y7 @% {9 Ithe literature by which the MSCs exert immunodulatory & K/ G' i8 c0 d) d S7 ~
effects. It should be pointed out that MSCs themselves 0 B0 S7 D. s' K
are objects of cytokine regulation. Hypothetical mecha-# ~, u$ x) m4 n# f4 j( R: y/ s
nisms by which the MSCs exert their immunoregula-
) ?2 L9 X% q9 {! e+ }/ D. rtory effects are also discussed in this review. These ) T- a+ A- H) `$ t
mechanisms may either influence the target immune 5 S4 ^7 X. c. Q, o
cells directly or indirectly by affecting the activities of
* |5 |. e5 D; t3 e2 T( gpredominantly dendritic cells. Chemokines are also dis-
5 x2 d( I$ z2 {7 ecussed as participants in this process by recruiting cells 5 s, A$ e5 m: E6 G* r( A3 r
of the immune systems and thus making them targets
1 ?: f; {+ o7 a$ n6 B3 }of immunosuppression. This review aims to present and
' |7 i3 N- T/ u( L1 M% Odiscuss the published data and the personal experience
; ?% a% L- y+ A0 tof the authors regarding cytokines secreted by MSCs
, `- O- H- T% e7 y9 C1 Dand their effects on the cells of the immune system.
) \! U2 C' s9 R9 w* C3 C1 ]" P; f© 2014 Baishideng Publishing Group Inc. All rights reserved.$ V" e/ ^( D" s' ?/ B6 w: |
Key words: Mesenchymal stem cells; Immunomodula-0 A" ?% X+ w' Q" X& {8 T: w
tion; Cytokines; Chemokines; Dendritic cells0 `& j, ~/ p9 c ~
Core tip: Autoimmune diseases affect approximately 5%
3 y- R9 d" t- g) bof the human population, leading to serious disability
7 w2 v! r6 p7 D! T# q1 m7 L0 uand effective methods to treat these diseases are still
z) B- i7 V% \ l" V. V; t% g1 o" Tnot perfect. Mesenchymal stem cells (MSCs) are as-
* P$ c q9 q3 Z5 [7 V Psumed to be promising agents, both for regenerative - k- v s& W7 w* ~& [3 o+ Y* y2 \
medicine and cell therapy for autoimmune disorders. 1 k |& {9 ]) T9 B, O
Under the influence of some factors, mesenchymal : I% u4 u, S$ j0 \+ |7 v% t
stem cells secrete cytokines which induce suppression & T' x5 \; q6 y' q4 ~+ v
of the immune response. Studies on the secreted cy-
8 B# k, y( y, n% c: a4 t, wtokines and the precise mechanisms involved in these 7 ?- G2 G R X* I' ^4 ?
suppressive mechanisms would create possibilities for & U+ S/ }# O/ _, {' R3 Y
effcient application of MSCs as a therapeutic means for
$ K& ?2 b- i0 F& \* i; U1 Wtreatment of autoimmune diseases.
: x5 Q4 H, B% o! _7 b. k8 jKyurkchiev D, Bochev I, Ivanova-Todorova E, Mourdjeva M, 8 w" ], Z3 ~% g
REVIEW6 V: U m, t8 O' D; ]
Submit a Manuscript: http://www.wjgnet.com/esps/
! O& W6 H6 i+ N" P' r" rHelp Desk: http://www.wjgnet.com/esps/helpdesk.aspx
& j: [* U3 `6 ^3 uDOI: 10.4252/wjsc.v6.i5.5528 `! z5 M: A, ^# y
World J Stem Cells 2014 November 26; 6(5): 552-570
! h4 Z% ?. v6 r) pISSN 1948-0210 (online)1 `: \- d5 j; x* C x& r
© 2014 Baishideng Publishing Group Inc. All rights reserved. |
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发表于 2014-12-7 23:28
