Kakabadze Zurab, Paresishvili Teona
Department of Clinical Anatomy, Tbilisi State Medical University 0186 Tbilisi, Georgia.
Am J Cancer Res. 2023 Sep 15;13(9):4192-4207. eCollection 2023.
This study demonstrates the possibility of tumor decellularization in living animals. Subcutaneous Ehrlich tumor induced by isolated Ehrlich ascitic carcinoma cells in mice was used as a model. The study also presents methods for ex vivo decellularization of human gastric adenocarcinoma (HGA) and hepatocellular carcinoma (HCC) induced by diethylnitrosamine (DEN) in rat. Sodium dodecyl sulfate (SDS) and Triton X-100 were used as detergents for tumor decellularization. The detergents for HGA and HCC were administered through organ vessels. For intravital decellularization of Ehrlich's subcutaneous tumor, detergents were injected directly into the tumor parenchyma. The results of the study showed that the effectiveness of tumor decellularization using SDS and Triton X-100 depended on the size, structure, stiffness and density of the tumor, as well as on the concentration, route and speed of detergent administration. The study also showed that an hour after the initiation of decellularization, the central part of Ehrlich's tumor changed the color, and after three hours, it completely acquired a translucent white color. Chemical contamination of tissues surrounding the tumor with the detergents was not observed. Histological studies showed the complete absence of all cellular components of Ehrlich's tumor and a slightly deformed extracellular matrix (ECM). There were no loco-regional recurrences or metastases of Ehrlich's tumor within 150 days after decellularization. The developed intravital decellularization method allows the effective removal of the cellular components and the DNA content of Ehrlich's subcutaneous tumor without compromising animal health. Additionally, this method can destroy tumor ECM, which will significantly improve the delivery of anticancer drugs to the tumor cells. However, more detailed and extensive studies are needed to develop an in vivo technique for isolated decellularization of the tumor or a part of the organ with the tumor. It is also necessary to identify less toxic decellularization agents and to develop the most efficient route for their delivery to the tumor cells.
本研究证明了在活体动物中使肿瘤脱细胞的可能性。将分离的艾氏腹水癌细胞诱导的小鼠皮下艾氏肿瘤用作模型。该研究还介绍了对大鼠二乙基亚硝胺（DEN）诱导的人胃腺癌（HGA）和肝细胞癌（HCC）进行离体脱细胞的方法。十二烷基硫酸钠（SDS）和 Triton X - 100用作肿瘤脱细胞的去污剂。用于HGA和HCC的去污剂通过器官血管给药。对于艾氏皮下肿瘤的活体脱细胞，去污剂直接注入肿瘤实质。研究结果表明，使用SDS和Triton X - 100进行肿瘤脱细胞的有效性取决于肿瘤的大小、结构、硬度和密度，以及去污剂给药的浓度、途径和速度。研究还表明，脱细胞开始一小时后，艾氏肿瘤的中央部分颜色发生变化，三小时后，它完全变成半透明的白色。未观察到肿瘤周围组织被去污剂化学污染。组织学研究显示艾氏肿瘤的所有细胞成分完全缺失，细胞外基质（ECM）略有变形。脱细胞后150天内，艾氏肿瘤没有局部复发或转移。所开发的活体脱细胞方法能够有效去除艾氏皮下肿瘤的细胞成分和DNA含量，而不损害动物健康。此外，该方法可以破坏肿瘤ECM，这将显著改善抗癌药物向肿瘤细胞的递送。然而，需要更详细和广泛的研究来开发一种体内技术，用于对肿瘤或带有肿瘤的器官部分进行单独脱细胞。还需要确定毒性较小的脱细胞剂，并开发将其递送至肿瘤细胞的最有效途径。
