Izolacija, karakterizacija i funkcionalna svojstva humanih matičnih ćelija masnog tkiva

Abstract

modulatorna svojstva zahvaljujući kojima se intenzivno izuĉava njihova primena u regenerativnoj medicini i ćelijskoj terapiji. Mezenhimske matiĉne ćelije (MMĆ) su rasprostranjene u mnogim tkivima i organima i izolovane su iz brojnih adultnih i neonatalnih tkiva. Najvažnije karakteristike MMĆ su samoobnavljanje i sposobnost diferenciranja u ćelije mezenhimskog (osteogene, adipogene, hondrogene, miogene), ali i ektodermalnog i endodermalnog porekla. Iako su ove osobine osnova za njihovu potencijalnu terapijsku primenu, mehanizmi regulacije brojnih funkcija MMĆ, kao i same diferencijacije nisu dovoljno ispitani i objašnjeni, što upućuje na neophodnost detaljnih analiza pre njihove kliniĉke primene. Kako su prvootkrivene MMĆ izolovane iz kostne srži, ispitivanja njihove uloge u procesu hematopoeze, ali i transplantacijama hematopoetskih matiĉnih ćelija, usmerila su aktuelna istraživanja na interakcije MMĆ sa ćelijama imunskog sistema, pri ĉemu je pokazano da su ove interakcije dvosmerne prirode i uzrokuju promene fenotipa i funkcionalnih osobina i MMĆ i imunskih ćelija. Poznato je da MMĆ svoje delovanje na imunske ćelije ostvaruju kako direktnim ćelijskim kontaktima, tako i preko brojnih solubilnih faktora koje produkuju, pri ĉemu molekularna osnova mehanizama modulacije imunskog odgovora nije u potpunosti poznata. Široka rasprostranjenost, multipotentni potencijal diferencijacije i imunomodulatorna svojstva, ĉine MMĆ važnim uĉesnicima u procesu reparacije oštećenih tkiva, u kojem produkujući brojne solubilne faktore uĉestvuju u svim fazama obnavljanja oštećenog tkiva: regulaciji aktivacije i mobilizacije imunskih ćelija, angiogenezi, mobilizaciji fibroblastnih ćelija, obnavljanju i remodelovanju ekstracelularnog matriksa. Kako su ovi procesi ukljuĉeni i u razvoj tumorskog tkiva, mnoga savremena istraživanja usmerena su na prouĉavanje interakcija MMĆ i tumorskih ćelija. Pokazano je da MMĆ mogu biti privuĉene u tumorsku mikrosredinu posredstvom inflamatornih faktora prisutnih u tumorskom tkivu, ali njihovo delovanje, kao i mehanizmi i posledice interakcija sa tumorskim ćelijama još uvek nisu razjašnjeni...

Numerous studies demonstrated that stem cells possess regenerative and modulatory properties and therefore their application in regenerative medicine and cell therapy is intensively considered. Mesenchymal stem cells (MSCs) are distributed in many tissues and organs, and have been isolated from numerous adult and perinatal tissues. The selfrenewal and capacity for differentiation into mesodernal cell types, such as osteoblasts, chondrocytes, adipocytes, but also into cells of ectodermal and endodermal origin, are the most important chracteristics of MSC. Although this properties provide MSCs pivotal role in regenerative medicine, mechanisms involved in regulation of differentiation, as well as in the other functions of MSCs are only partly understood, and therefore additional studies are necesseary before their clinical application. Discovery of bone marrow MSCs and investigation of their role in hematopoiesis and hematopoietic stem cells transplantation, focused current research toward mutual interactions between MSCs and immune cells, which affect the phenotype and functions of both immune cells and MSCs. Immunomodulatory activity of MSCs could be mediated by direct cell contact or by secreted molecules, but the mechanisms by which MSCs exert this activity are still unclear. Due to their wide distribution, multipotent differentiation potential and immune properties, MSC are also important participants in tissue renewal and repair. However, it was shown that beside the innate tropism for injured tissue, MSCs have the capacity to home to tumors and participate in tumor stroma formation. Additionally recent studies indicated that the proangiogenic, anti-apoptotic and/or immunomodulatory properties of MSCs may also act together as tumor promoters, raising significant safety concerns. Adipose tissue is the most distributed tissue in adult organism, consisting predominantly of adipocytes, but also progenitor cells and MSCs which contribute to tissue organization maintenance, as well as heterogeneous population of many other cell types, including immune cells. Adipose tissue is also the most abundant tissue in breast region, and breast cancer is the most frequent malignancy in women today, often associated with the reconstructive surgery as an integral part of breast cancer treatment in which adipose tissue engineering and structural fat grafting, as well as the use of MSCS, are being applied as options for regenerative therapy...