MSC delujejo predvsem preko parakrinih mehanizmov: izkazujejo protivnetne, antiapoptotske, antioksidativne, proangiogene, protimikrobne in antifibrotične učinke ter izboljšujejo funkcijo epitelijske in endotelijske pregrade ter odstranjevanje tekočine iz alveolov pri ARDS in drugih poškodbah pljuč (Harrell idr., 2019; Fernández-Francos idr., 2021; Qin in Zhao, 2020; Lopes-Pacheco idr., 2019; Behnke idr., 2020). MSC uravnavajo prirojeni in pridobljeni imunski odziv, preusmerjajo makrofage v reparativni fenotip M2 ter lahko v eksperimentalnih modelih delno podpirajo regeneracijo alveolarnega epitelija ali se diferencirajo v celicam AT2 podobne fenotipe (Harrell idr., 2019; Yuan idr., 2024; Zhang idr., 2025; Lopes-Pacheco idr., 2019).
| Bolezen / klinično stanje | Vloga MSC (dokazi) | Ključne ugotovitve | Reference |
|---|---|---|---|
| ARDS / COVID ARDS | Zmanjšanje citokinske nevihte, izboljšanje pregrade, preživetje (živalski modeli; zgodnje klinične študije, študija H7N9) | Dokazana varnost; nekateri signali nižje smrtnosti, potrebne večje randomizirane študije | (Fernández-Francos et al., 2021; Qin & Zhao, 2020; Lopes-Pacheco et al., 2019; Chen et al., 2020) |
| KOPB in astma | Zmanjšanje vnetja, oksidativnega stresa in remodeliranja; izboljšanje pljučne funkcije (pretežno predklinično; manjše študije) | Klinične raziskave potrjujejo varnost, učinkovitost za zdaj omejena | (Cruz & Rocco, 2020; Harrell et al., 2019; Abbaszadeh et al., 2022; Wang et al., 2021; Lai & Guo, 2024; Wecht & Rojas, 2016; Antoniou et al., 2018) |
| Idiopatska pljučna fibroza / kronične fibrozne intersticijske bolezni | Antifibrotični in regenerativni učinki v modelih; faze I/II potrjujejo varnost | Najprimernejše verjetno zgodnje faze bolezni; dolgoročni učinki neznani | (Cruz & Rocco, 2020; Yuan et al., 2024; Chen et al., 2021; Wecht & Rojas, 2016; Antoniou et al., 2018) |
| Bronhopulmonalna displazija (BPD), pljučna arterijska hipertenzija (PAH), silikoza, pljučnica | Eksperimentalna in zgodnja klinična uporaba, zlasti z MSC iz popkovnice (UC-MSC) | Koristi predvsem v živalskih modelih | (Cruz & Rocco, 2020; Fernández-Francos et al., 2021; Zhang et al., 2025; Chen et al., 2021; Mohammadipoor et al., 2018) |
Slika 1: Ključne pljučne indikacije, ki se raziskujejo za terapijo z MSC.
Zunajcelični vezikli (EV) oziroma eksosomi, pridobljeni iz MSC, reproducirajo številne koristne učinke celic ob nižji imunogenosti, manjšem tveganju za tumorigenezo in enostavnejšem shranjevanju. Učinkovitost so pokazali v modelih KOPB, astme, fibroze in ARDS (Abbaszadeh idr., 2022; Zhang idr., 2025; Yiming idr., 2022; Mohammadipoor idr., 2018). Pristopi, ki temeljijo na sekretomu, se vse bolj uveljavljajo kot obetavna »brezcelična« terapevtska strategija (Fernández-Francos idr., 2021; Yiming idr., 2022; Mohammadipoor idr., 2018).
V več kot 100 kliničnih raziskavah s področja pulmologije se zdi intravenska uporaba MSC (najpogosteje iz kostnega mozga ali popkovnice) varna, vendar so učinki na pljučno funkcijo, simptome in preživetje za zdaj skromni in nedosledni (Cruz in Rocco, 2020; Wang idr., 2021; Chen idr., 2021; Antoniou idr., 2018). Ključna odprta vprašanja vključujejo optimalni vir celic (MSC iz popkovnice so lahko učinkovitejše pri ARDS), ustrezen odmerek, način aplikacije, čas zdravljenja ter potrebo po ponavljajočih se aplikacijah ali genski/modifikacijski pripravi za povečanje terapevtske učinkovitosti (Cruz in Rocco, 2020; Fernández-Francos idr., 2021; Wang idr., 2021; Regmi idr., 2024).
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