建立人源化异种移植模型,作为骨肉瘤肺转移的活体研究对象

IF 4.1 Q2 IMMUNOLOGY Immunotherapy advances Pub Date : 2024-03-23 DOI:10.1093/immadv/ltae002
Farhana Khamarudin, M. Muhamad, Mohamad Johari I, Wan Nor I’zzah WMZ, Mardiana Abdul Aziz, Nurul Raudzah Adib Ridzuan, S. Ab-Rahim
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引用次数: 0

摘要

人源化异种移植模型和癌细胞系被广泛用于癌症研究中的临床前药物评估、生物学研究和靶向治疗策略。人源化小鼠模型是一种经过基因改造的实验室小鼠,含有特定的人类基因、细胞或组织。通过在啮齿类动物中引入人类特异元素,研究人员可以更准确地再现人类的生理和病理过程。骨肉瘤(OS)缺乏合适的动物模型,这阻碍了对骨肉瘤转移进展内在机制的了解。转移对骨肉瘤的预后和治疗有显著影响。深入了解转移的机制和发生情况可能有助于肿瘤学家改进治疗方法。因此,建立肺转移性骨肉瘤模型以研究其进展的基本生物学特性非常重要。本研究利用HOS-143B细胞系建立了肿瘤小鼠模型,并将其分别注射到雄性NOD.SCID gamma(NSG)小鼠的两个部位:肌肉注射(后腿)和皮下注射(背部)。原发性和转移性肿瘤的大小通过触诊诱发肿瘤的区域进行监测,并使用数字卡尺进行量化。病理学家对转移瘤进行了 H&E 染色。结果表明,注射 100 万个癌细胞的小鼠无法产生肿瘤。同时,注射 300 万个癌细胞的小鼠在接种癌细胞 25 天后出现肿瘤发生和肺转移。总之,本研究成功建立了肺转移性 OS 小鼠模型,可用于 OS 的生物学研究。这些研究结果表明,该模型对临床试验前的安全性和有效性至关重要,可加速从基础研究到治疗应用的转化。
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Establishment of Humanised Xenograft Models as In Vivo Study for Lung Metastasis of Osteosarcoma
Humanized xenograft models and cancer cell lines are widely used for preclinical drug evaluation, biological studies, and targeted therapy strategies in cancer research. A humanised mouse model is a laboratory mouse that has been genetically modified to contain specific human genes, cells, or tissues. By introducing human-specific elements into rodents, researchers can create a more accurate representation of human physiological and pathological processes. Lacking an appropriate animal model for osteosarcoma (OS), hindered understanding of underlying mechanisms in OS metastasis progression. Markedly, metastasis influences the prognosis and treatment of osteosarcoma. Gaining insight into the mechanisms and occurrences of metastasis could potentially facilitate oncologists in improving therapies. Hence, it is important to develop a lung metastatic OS model to study the basic biology of its progression. This study has established a tumour-bearing mouse model using HOS-143B cell line which was injected into male NOD.SCID gamma (NSG) mice at two locations; intramuscularly (hind leg) and subcutaneously (back) respectively. The primary and metastatic tumour size was monitored by palpating the area of tumour induced and quantified using digital calliper. H&E staining was performed by pathologist to confirm metastasis. Our results showed that mice injected with 1 million cancer cells were unable to produce tumours. Meanwhile, mice injected with 3 million cancer cells showed tumour development and lung metastasis after 25 days of cancer cell inoculation. In conclusion, this study has successfully established a lung metastatic OS mouse model that could be useful for biological studies of OS. These findings imply that this model is essential for safety and efficacy before clinical trials, accelerate the translation from basic research to therapeutic applications.
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