Evaluacija 3D modela osteosarkoma: eksperimentalna studija i matematičko modelovanje odgovora na lek Naučni rad
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Osteosarkom i dalje predstavlja značajan klinički izazov, sa lošim ishodima u slučaju metastaza i sporim napretkom u razvoju novih terapija. U ovom radu je prethodno razvijen 3D model osteosarkoma, koji se sastoji od makroporoznih alginatnih nosača sa česticama hidroksiapatita, koji oponašaju koštano tkivo, i protočnog bioreaktora, procenjen kao alat za ispitivanje antitumorskih lekova. Ćelija mišjeg osteosarkoma (K7M2-wt) zasejane su na nosače (15×10⁶ ćelija po cm³) i gajene jedan dan u statičnim uslovima. U dve eksperimentalne serije nosači su potom izloženi doksorubicinu (1 µg cm⁻³) u protočnim uslovima tokom 1 ili 3 dana (površinska brzina 40 µm s⁻¹), čime su simulirani uslovi nakon resekcije tumora, sa pretežno pojedinačnim ili slabo agregiranim ćelijama. U dve dodatne serije isti tretmani primenjeni su nakon 7 dana protočne kulture, kada su se formirali kompaktni sferoidi, čime je simuliran razvijen tumor. Histološka analiza i MTT test korišćeni su za procenu morfologije ćelija i njihove metaboličke aktivnosti. Kratkotrajni tretman imao je zanemarljiv efekat, dok je produžena izloženost značajno smanjila metaboličku aktivnost pojedinačnih ćelija, dok su sferoidne strukture pokazale povećanu otpornost na doksorubicin. Radi objašnjenja rezultata dobijenih u prve dve eksperimentalne serije, razvijen je matematički model koji opisuje transport leka, intracelularnu akumulaciju, proliferaciju ćelija i njihovo odumiranje. Model je uspešno opisao početnu fazu tretmana, ali je precenio efekat produžene izloženosti, ukazujući na mogućnost postojanja dodatnih mehanizama rezistencije. Sveukupno, rezultati potvrđuju potencijal ovog 3D modela za ispitivanje antitumorskih lekova.
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Funding data
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Science Fund of the Republic of Serbia
Grant numbers 7503 -
Ministarstvo Prosvete, Nauke i Tehnološkog Razvoja
Grant numbers 451-03-34/2026-03/200135;451-03-34/2026-03/200110)
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