탈세포화 간 지지체를 이용한 간세포암 오가노이드의 세포 증식 = Cellular expansion of hepatocellular carcinoma organoids using decellularized liver scaffolds.

다국어 초록 (Multilingual Abstract)

Background: A decellularized liver scaffold (DLS) is a three-dimensional acellular type of extracellular matrix created by removing cellular components from liver tissue. Hepatocellular carcinoma (HCC) organoids are a useful experimental model.

Methods: HCC organoids from patient-derived xenografts (PDX), liver organoids, and HepG2 cell line cells were expanded by cultivation in a murine DLS.

Results: HCC and liver organoids were generated from HCC PDX and human liver tissues, respectively. Expression of HepPar1, EpCAM, α-fetoprotein, keratin-7, and keratin-19 was detected in normal liver tissue, HCC tissue, HCC PDX, and HCC organoids. Fifteen murine DLSs were created, and complete absence of liver cells was confirmed histologically by Masson trichrome and periodic acid Schiff staining. Culture of HCC organoids in the DLS resulted in expansion of numerous HCC cells, which were scattered throughout the whole DLS framework. Expression of Keratin-7 was abundant, indicating widely scattered progenitor cells. Culture of the HepG2 cell line in the DLS resulted in sparse scattering of cells across the DLS framework. Human hepatocyte organoids could not be cultivated within the murine DLS framework.

Conclusions: The collagen framework of DLS facilitates proliferation of HCC organoids. Thus, culture of HCC organoids within DLS appears to be an effective method of driving rapid cell expansion, although not for HepG2 cells and liver organoids. Further studies are necessary to validate the biological and oncological equivalence between seeded HCC organoids and rapidly cultivated HCC organoids within DLS.

목차 (Table of Contents)

• Abstract i
• Contents ii
• List of Figures iii
• Abbreviatons iv
• Introduction 1
• Materials and Methods 2
• Results 5
• Discussion 8
• Conclusions 14
• 국문 요약(Summary in Korean) 28