Od nukleisanih do ex vivo manipulisanih matičnih ćelija – osavremenjena biološka i klinička sinapsa

Bela Balint, Mirjana Pavlovic, Milena Todorovic

Med reč 2020; 1(1): 1–9

DOI: https://doi.org/10.5937/medrec2001001B

Apstrakt

Hematopoetske matične ćelije (MĆ) odgovorne su za produkciju i obnovu (proliferacija) opsežne količine funkcionalno kompetentnih krvnih ćelija (diferencijacija) tokom celog života, istovremeno one održavaju sposobnost sopstvene reprodukcije (samoobnavljanje). Složena mreža interaktivnih supstanci i faktora organizuje i obezbeđuje preživljavanje, sazrevanje i umnožavanje MĆ.

Hemobiološki događaji u kostnoj srži (KS) sinhronizovani/uravnoteženi su ekstracelularnim matriksom i mikrookolinom koji obezbeđuju stromalne ćelije. Ove ćelije – uključujući makrofage, fibroblaste, dendritske, endotelske i druge ćelije – deluju stimulativno na MĆ, oslobađanjem specifičnih hematopoetskih faktora rasta. Neki drugi citokini koje izlučuju stromalne ćelije regulišu adhezivne molekule iskazane na MĆ, omogućavajući im da ostanu u KS ili da migriraju u područje gde je potreban odgovarajući specifičan tip ćelije. Na taj način, hematopoetske MĆ je moguće definisati kao ćelije visokog proliferativnog kapaciteta i ogromnog potencijala da se diferentuju u sve vrste krvnih ćelija ili u neke somatske ćelije (plastičnost MĆ) – kao što su kardiomiociti, miociti, osteociti, hondrociti, hepatociti, ali i endotelske ćelije.

Sve šira klinička primena ćelijski-posredovanih terapijskih pristupa rezultuje stalno rastućim potrebama u samim MĆ, ali i poboljšanjima operativnih procedura njihove ex vivo manipulacije. Osnovni cilj prikupljanja ćelija je da se dobije veći prinos i vijabilnost ili klonogenost MĆ. Cilj optimizovanih protokola krioistraživanja je da se minimizuju oštećenja ćelija (kriooštećenja). Uprkos činjenici da se različiti protokoli za prikupljanje i protokoli kriokonzervacije MĆ su već u rutinskoj upotrebi, brojna pitanja vezana za optimalne ex vivo manipulaciju MĆ još uvek nisu u potpunosti rešena.

Ovaj revijalni rad prikazuje osnovna saznanja i metodološke pristupe, kao i podatke koji omogućavaju napredak na stalno razvijajućim frontovima istraživanja na području MĆ. Studije (uključujući i naša istraživanja) koje procenjuju efikasnost i sigurnost terapijske primene MĆ (transplantacijska i regenerativna medicina) biće takođe ukratko predstavljene.

Ključne reči: matične ćelije, transplantacija, regenerativna medicina

Ceo tekst

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