EVALUAREA ACTIVITĂȚII ANTITUMORALE A CELULELOR STEM MEZENCHIMALE DERIVATE DIN ȚESUT ADIPOS

Abstract

The present study aimed to evaluate the antitumor activity of adipose tissue-derived mesenchymal stem cells (AT-MSC), cells obtained from rats isolation. The in vitro evaluation of the antitumoral activity was performed by co-culture of isolated AT-MSCs with the tumoral line of U87 glioblastoma, and for the in vivo evaluation of the antitumoral activity the same U87 line was injected in rats randomized into 3 study groups: the tumor control group, the group injected with saline solution and the group treated with AT-MSCs. By extrapolating of isolation technology of AT-MSCs and the data provided by the animal test models, the results of this study can be used to treat inflammatory lung diseases but also tumor pathologies in the human population.

Obiective. Studiul de fată a urmărit evaluarea activităţii antitumorale a celulelor stem mezenchimale derivate din ţesut adipos (AT-MSC), celule obţinute prin izolarea de la şobolan. Scopul este reprezentat de îmbunătăţirea metodelor terapeutice prin utilizarea celulelor stem mezenchimale ca o opţiune de tratament de susţinere atât în bolile infecţioase cât şi în afecţiunile tumorale.

Materiale şi metode. Pentru izolarea AT-MSC-urilor am utilizat 3 şobolani masculi Wistar albino. Evaluarea in vitro a activităţii antitumorale s-a realizat prin co-cultivarea AT-MSC-urilor izolate cu linia tumorală de glioblastom U87, iar pentru evaluarea in vivo a activităţii antitumorale aceeaşi linia tumorală U87 a fost injectată la şobolani randomizaţi în 3 loturi de studiu: lotul martor tumoral, lotul martor injectat cu soluţie salină şi lotul tratat cu AT-MSC-uri. Probele tumorale recoltate au fost colorate cu hematoxilină-eozină pentru analizele histopatologice, iar expresia Ki-67 a fost evaluată după colorarea imunohistochimică folosind anticorpi specifici.

Rezultate şi discuţii. AT-MSC-urile au fost identificate ca fiind celule stem mezenchimale (MSC) prin morfologie, identificare fenotipică şi capacitatea de a induce diferenţierea osteogenă, condrogenă şi adipogenă. Prin cultivarea asociată a celor 2 linii celulare AT-MSC şi U87 s-a observat o întârziere semnificativă a creşterii liniei tumorale U87, în comparaţie cu aceeaşi linie crescută în grupul control. La testările in vivo lotul tratat cu AT-MSC -uri a prezentat fenomenul de supresie a tumorilor.

Concluzii. AT-MSC-urile sunt unul dintre cele mai promiţătoare tipuri de MSC, care pot fi obţinute cu uşurinţă prin proceduri minim invazive şi pot înlocui cu succes prelevarea MSC din măduva osoasă. Prin extrapolarea tehnologiei de izolare a AT-MSC-urilor şi a datelor furnizate de modelele de testare animale, rezultatele studiului pot fi utilizate pentru tratarea bolilor inflamatorii pulmonare dar şi a afecţiunilor tumorale în cazul populaţiei umane.

Sursa de finanţare: lucrare desfăşuratăîn cadrul PSCD al MApN 2022 - ProiectADIPOSTEM.

Objectives. The present study aimed to evaluate the antitumor activity of adipose tissue-derived mesenchymal stem cells (AT-MSC), cells obtained from rats isolation. The goal is to improve the therapeutic methods by using mesenchymal stem cells as a supportive treatment option in both infectious and tumoral diseases.

Materials and methods. For the isolation of AT-MSCs we used 3 male Wistar albino rats. The in vitro evaluation of the antitumoral activity was performed by co-culture of isolated AT-MSCs with the tumoral line of U87 glioblastoma, and for the in vivo evaluation of the antitumoral activity the same U87 line was injected in rats randomized into 3 study groups: the tumor control group, the group injected with saline solution and the group treated with AT-MSCs. The harvested tumor samples were stained with hematoxylin-eosin for histopathological analyses, and Ki-67 expression was evaluated after immunohistochemical staining using specific antibodies.

Results and discussion. AT-MSCs were identified as mesenchymal stem cells (MSCs) by morphology, phenotipical identification and by the ability to induce osteogenic, chondreogenic and adipogenic differentiation. By co-culture of AT-MSCs with the U87 tumoral cell line, a significant delay in the growth of the U87 tumor line was observed, compared to the same line grown in the control group. In the in vivo tests, the group treated with AT-MSCs showed tumor suppression.

Conclusions. AT-MSCs are one of the most promising types of MSCs, that can be easily obtained by minimally invasive procedures and that can succesfully replace MSC bone marrow prelevation. By extrapolating of isolation technology of AT-MSCs and the data provided by the animal test models, the results of this study can be used to treat inflammatory lung diseases but also tumor pathologies in the human population.

Funding source: The study was carried out within the PSCD project ADIPOSTEM, funded by Ministry of Defence.