Yamamoto Takeshi, Miyoshi Hayato, Mima Shinji, Kamata Hiroyuki, Ishikawa Shohei, Nozaki Yuji, Takagi Hisayoshi, Kakinuma Chihaya, Yao Takashi
Department of Human Pathology, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
HOIST Co., Ltd., TechnoAlliance Complex. C-807 Osaka University, 2-8 Yamadaoka, Suita, Osaka 565-0871, Japan.
J Toxicol Pathol. 2025 Apr;38(2):139-145. doi: 10.1293/tox.2024-0054. Epub 2024 Dec 30.
Bladder cancer is treated by surgical removal of the tumor followed by injection of anticancer drugs or the Bacillus Calmette-Guerin vaccine. However, there are insufficient effective drug options depending on the risk category of bladder cancer. One of the reasons for this is the limited number of suitable experimental models that reproduce the pathology of bladder cancer for each risk category. There has been increasing interest in the patient-derived xenograft model as an experimental model to reproduce the original nature of the tumor in a patient. However, there are unresolved problems regarding its practical use, such as the low success rate of engraftment, variation in the growth rate between experiments, and the lack of a reliable method to prepare a patient-derived xenograft model from cryopreserved tumor tissue. In this study, the effect of scaffold material on the preparation of a bladder cancer patient-derived xenograft model was investigated and it was found that gelatin/polyethylene glycol-based hydrogel offers advantages for engraftment of cryopreserved bladder cancer tissue. It was shown that the proliferation of cryopreserved bladder cancer cells was promoted with less necrosis and thrombi around the tissue when transplanted into immunodeficient animals with glycol-based hydrogel compared to transplantation with Matrigel or without any scaffold. This study proposes a new method to generate patient-derived xenograft models from cryopreserved bladder cancer tissue, which is expected to have improved proliferation activity after transplantation.
膀胱癌的治疗方法是手术切除肿瘤，随后注射抗癌药物或卡介苗疫苗。然而，根据膀胱癌的风险类别，有效的药物选择并不充足。其原因之一是能够重现各风险类别膀胱癌病理特征的合适实验模型数量有限。作为一种能在患者体内重现肿瘤原始特性的实验模型，患者来源的异种移植模型越来越受到关注。然而，其实际应用中仍存在一些未解决的问题，比如移植成功率低、实验间生长速率存在差异，以及缺乏一种从冷冻保存的肿瘤组织制备患者来源异种移植模型的可靠方法。在本研究中，研究了支架材料对制备膀胱癌患者来源异种移植模型的影响，发现基于明胶/聚乙二醇的水凝胶在冷冻保存的膀胱癌组织移植方面具有优势。结果表明，与使用基质胶或不使用任何支架进行移植相比，将冷冻保存的膀胱癌细胞与基于乙二醇的水凝胶一起移植到免疫缺陷动物体内时，组织周围坏死和血栓较少，且细胞增殖得到促进。本研究提出了一种从冷冻保存的膀胱癌组织生成患者来源异种移植模型的新方法，预计该模型移植后增殖活性会有所提高。
