MSC djeluju ponajprije putem parakrinih mehanizama: iskazuju protuupalne, antiapoptotske, antioksidativne, proangiogene, antimikrobne i antifibrotične učinke te poboljšavaju funkciju epitelne i endotelne barijere i uklanjanje tekućine iz alveola kod ARDS-a i drugih ozljeda pluća (Harrell i sur., 2019; Fernández-Francos i sur., 2021; Qin i Zhao, 2020; Lopes-Pacheco i sur., 2019; Behnke i sur., 2020).
MSC reguliraju urođeni i stečeni imunosni odgovor, preusmjeravaju makrofage u reparativni fenotip M2 te u eksperimentalnim modelima mogu djelomično poduprijeti regeneraciju alveolarnog epitela ili se diferencirati u fenotipove slične AT2 stanicama (Harrell i sur., 2019; Yuan i sur., 2024; Zhang i sur., 2025; Lopes-Pacheco i sur., 2019).
| Bolest / kliničko stanje | Uloga MSC (dokazi) | Ključni nalazi | Reference |
|---|---|---|---|
| ARDS / COVID ARDS | Smanjenje citokinske oluje, poboljšanje barijere, preživljenje (životinjski modeli; rane kliničke studije, studija H7N9) | Dokazana sigurnost; pojedini signali niže smrtnosti, potrebne veće randomizirane studije | (Fernández-Francos et al., 2021; Qin & Zhao, 2020; Lopes-Pacheco et al., 2019; Chen et al., 2020) |
| KOPB i astma | Smanjenje upale, oksidativnog stresa i remodeliranja; poboljšanje plućne funkcije (pretežno pretklinički podaci; manje studije) | Klinička istraživanja potvrđuju sigurnost, učinkovitost zasad ograničena | (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 plućna fibroza / kronične fibrozne intersticijske bolesti | Antifibrotični i regenerativni učinci u modelima; faze I/II potvrđuju sigurnost | Vjerojatno najprikladnije rane faze bolesti; dugoročni učinci nepoznati | (Cruz & Rocco, 2020; Yuan et al., 2024; Chen et al., 2021; Wecht & Rojas, 2016; Antoniou et al., 2018) |
| Bronhopulmonalna displazija (BPD), plućna arterijska hipertenzija (PAH), silikoza, upala pluća | Eksperimentalna i rana klinička primjena, osobito s MSC iz pupkovine (UC-MSC) | Koristi uglavnom u životinjskim modelima | (Cruz & Rocco, 2020; Fernández-Francos et al., 2021; Zhang et al., 2025; Chen et al., 2021; Mohammadipoor et al., 2018) |
Slika 1: Ključne plućne indikacije koje se istražuju za terapiju MSC-om.
Izvanstanični vezikuli (EV), odnosno egzosomi dobiveni iz MSC, reproduciraju mnoge korisne učinke stanica uz nižu imunogenost, manji rizik od tumorigeneze i jednostavnije skladištenje. Učinkovitost je pokazana u modelima KOPB-a, astme, fibroze i ARDS-a (Abbaszadeh i sur., 2022; Zhang i sur., 2025; Yiming i sur., 2022; Mohammadipoor i sur., 2018). Pristupi temeljeni na sekretomu sve se više afirmiraju kao obećavajuća „bezstanična“ terapijska strategija (Fernández-Francos i sur., 2021; Yiming i sur., 2022; Mohammadipoor i sur., 2018).
U više od 100 kliničkih istraživanja iz područja pulmologije intravenska primjena MSC (najčešće iz koštane srži ili pupkovine) pokazuje se sigurnom, no učinci na plućnu funkciju, simptome i preživljenje zasad su skromni i nedosljedni (Cruz i Rocco, 2020; Wang i sur., 2021; Chen i sur., 2021; Antoniou i sur., 2018).
Ključna otvorena pitanja uključuju optimalni izvor stanica (MSC iz pupkovine mogu biti učinkovitije kod ARDS-a), odgovarajuću dozu, način primjene, vrijeme liječenja te potrebu za ponovljenim primjenama ili genetskom/modifikacijskom pripremom radi povećanja terapijske učinkovitosti (Cruz i Rocco, 2020; Fernández-Francos i sur., 2021; Wang i sur., 2021; Regmi i sur., 2024).
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