Functional characterization of primary mesenchymal stem cells under proinflammatory and altered oxygenation conditions

Mezenhimske matične ćelije (MMĆ) deo su populacije multipotentnih matičnih ćelija prisutnih u mnogim adultnim tkivima gde učestvuju u održavanju homeostaze. Zahvaljujući sposobnosti samoobnove, potencijalu diferenciranja u specijalizovane ćelije mezodermskog porekla i imunomodultatornim svojstvima, ove nediferencirane ćelije karakteriše širok opseg potencijalne terapijske primene. Regenerativnom kapacitetu MMĆ doprinosi i sposobnost migracije do oštećenih tkiva gde učestvuju u njihovom obnavlјanju što ove ćelije čini pogodnim za ćelijsku terapiju. Mezenhimske MĆ su do sada izolovane iz velikog broja adultnih tkiva i mnoge studije potvrdile su da njihov regenerativni potencijal u velikoj meri zavisi od izvora iz kojeg potiču. Prvobitno su izolovane iz kostne srži koja je do sada najčešće korišćen izvor MMĆ, međutim zbog invazivnih metoda izolacije i malog prinosa MMĆ, stvorena je potreba za alternativnim izvorima. Činjenica da su MMĆ izolovane i iz periferne krvi jedno je od značajnih otkrića iz ove oblasti i smatra se da ove ćelije najverovatnije vode poreklo iz kostne srži, međutim nije dovoljno poznato na koji način migriraju i bivaju privučene u oštećena tkiva. Poslednjih godina se kao povolјan izvor MMĆ sa potencijalnom primenom u regenerativnoj medicini sve češće pominju i perinatalna tkiva (pupčanik i placenta). Prednost pupčanika kao izvora MMĆ ogleda se u lakoj dostupnosti tkiva koje se smatra medicinskim otpadom, neinvazivnoj izolaciji ćelija i činjenici da su izolovane MMĆ po kapacitetu samoobnove i većoj ekspresiji markera pluripotentnost slične embrionalnim MĆ. Iako se već nekoliko decenija MMĆ intenzivno istražuju, uprkos velikom doprinosu nauci i medicini, o njihovom upkupnom terapijskom potencijalu se još uvek nedovoljno zna. Trenutno nije poznat univerzalan mehanizam terapijskog delovanja MMĆ, a mnogobrojni nalazi sve više u poslednje vreme upućuju da ponašanje i uloge MMĆ zavise od konteksta mikrosredine u kojoj obitavaju i/ili deluju, kao mestu integracije spolјnih signala koji određuju sudbinu MMĆ i usmeravaju ih ka određenoj funkciji...present in many adult tissues where they participate in maintaining of homeostasis. Due to their self-renewal capacity, differentiation potential into specialized cells of mesodermal origin and immunomodulatory features, these undifferentiated cells are characterized with wide range of potential therapeutic applications. Their ability to migrate towards damaged tissues where they participate in tissue repair, also contributes to their regenerative potential which makes them suitable for cell therapy. MSCs have so far been isolated from various adult tissues and many studies confirmed that MSCs’ regenerative potential depends largely on the suorce which they originate from. They were originaly isolated from bone marrow which has been the most commonly used source of MSCs so far, however due to invasive methods of isolation and low MSCs yield, there is a need for alternative sources of MSCs. The fact that these cells were isolated from peripheral blood is one of the significant discoveries in this area and it is believed that these MSCs are most likely to originate from bone marrow, but how they migrate and home to damaged tissues has not yet been elucidated completely. Perinatal tissues (umbilical cord and placenta) have been recently increasingly suggested as favourable sources of MSCs with potential applications in regenerative medicine. The advantage of umbilical cord as a source of MSCs is reflected in easy availability of tissue considered as medical waste, non-invasive cell isolation methods, and the fact that MSCs isolated from umbilical cord are similar to embryonic stem cells in the terms of self-renewal capacity and pluripotency markers’ expression. Eventhough MSCs have been extensively investigated for several decades, and despite their great contribution to science and medicine, their overall therapeutic potential is still poorly understood. Currently, there is no universal mechanism of MSCs’ therapeutic action known, and many findings have recently suggested that behaviour and roles of MSCs depend on the context of microenvironment in which they reside and/or act, as sites of integration of external cues that determine the fate of MSCs and govern them towards specific function..