Mezenhimske matične ćelije (MSC) pripadaju populaciji multipotentnih adultnih
matičnih ćelija koje se nalaze u mnogim tkivima gde ostvaruju važne uloge u
održavanju homeostaze. Zahvaljujući višestrukom potencijalu u regeneraciji tkiva,
regulaciji hematopoeze i imunomodulaciji, kao i relativno lakoj dostupnosti iz raznih
adultnih i perinatalnih tkiva, intenzivirana su istraživanja kako osnovne biologije MSC,
tako i ona usmerena ka mogućnosti njihove terapijske primene. Iako je u poslednjoj
deceniji došlo do značajnog i brzog napretka u razumevanju njihove prirode,
raznovrsnih funkcija i mehanizama njihovog delovanja, još smo daleko od
rasvetljavanja nekih osnovnih pitanja ključnih za njihovu efikasnu i bezbednu kliničku
primenu. Poslednjih godina se sve više uviđa značaj lokalne mikrosredine u
usmeravanju MSC ka obavljanju mnogobrojnih i često suprotstavljenih funkcija.
Interleukin-17 (IL-17) je plejotropni citokin sa značajnim ulogama u mnogim
fiziološkim i patološkim procesima organizma, poput inflamacije, imunskog odgovora i
regulacije hematopoeze. IL-17 svoje efekte ostvaruje uglavnom indirektno, delujući na
stromalne ćelije, modulišući u njima ekspresiju različitih solubilnih i membranskih
faktora. Iako su istraživanja uticaja IL-17 na proliferaciju i diferencijacju humanih i
mišjih MSC započeta, mnogi efekti, poput uticaja na regulatornu ulogu ovih ćelija u
hematopoezi i imunskom odgovoru, kao i mehanizmi i značaj njegovog delovanja na
MSC, još nisu dovoljno ispitani.
Cilj ovog istraživanja bio je da se izoluju i okarakterišu MSC iz kostne srži miša
(mBM-MSC) i utvrdi efekat IL-17 na fenotipske karakteristike, sposobnost višelinijske
diferencijacije, proliferaciju, kapacitet podržavanja hematopoeze i imunomodulatorne
sposobnosti ovih ćelija. Takođe, ispitivani su i mehanizami delovanja IL-17 na
8
mBM-MSC, uključujući aktivaciju signalnih puteva i ulogu NO kao posrednika u ovim
efektima...Mesenchymal stem cells (MSCs) are multipotent adult stem cells that are found in
many tissues where they play an important role in maintaining the tissue homeostasis.
Due to their enormous potential in tissue regeneration, regulation of hematopoiesis, and
immunomodulation, as well as the fact that they are readily available from numerous
adult and perinatal tissues, MSCs have been in the focus of basic and clinical research in
the last few decades. Although a significant and rapid progress in understanding the
nature, various functions, and mechanisms of action of MSCs has been made during the
last decade, we are still far from resolving some of the key issues that are necessary for
their effective and safe use in the clinics. The importance of the local microenvironment
in directing MSCs to perform their numerous and often conflicting functions have been
increasingly recognized over the recent years. Interleukin-17 (IL-17) is a pleiotropic
cytokine with important roles in many physiological and pathological processes, such as
inflammation, immune response, and regulation of hematopoiesis. This cytokine
achieves its functions indirectly, by modulating the expression of variety of soluble and
membrane-bound factors in stromal cells. Although some effects of IL-17 on the
proliferation and differentiation of MSCs have been demonstrated in human and mouse
models, other potential effects, such as the influence of this cytokine on the regulatory
role of MSCs in hematopoiesis and immune response, as well as the mechanisms and
the significance of its action, are not sufficiently elucidated.
The aim of this study was to isolate and characterize MSCs from mouse bone
marrow (mBM-MSCs) and to analyze the effects of IL-17 on their phenotype,
multilineage differentiation, proliferation, hematopoietic supportive capacity, and
immunomodulatory activity. The mechanisms of action, including the signaling
pathways and the role of NO as a mediator, were also examined..
