Park Tae Hwan, Rah Dong Kyun, Chang Choong Hyun, Kim Sung Young
*Institute for Human Tissue Restoration, Department of Plastic and Reconstructive Surgery, Yonsei University College of Medicine †Department of Plastic and Reconstructive Surgery, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine ‡Department of Biochemistry, College of Medicine, Konkuk University, Seoul, Korea.
J Craniofac Surg. 2016 Oct;27(7):1670-1673. doi: 10.1097/SCS.0000000000002901.
Recent advances on preclinical model based on patient-derived tumor xenografts have new insight into many clinical fields. According to our literature review, many authors believe that immunodeficient animals such as athymic rats and mice should be used to prevent tissue loss caused by acute rejection to establish patient-derived tumor xenografts models.However, recent advances showed that the microenvironment has gained attention as an important factor responsible for disease progression. Additionally, researchers attempt to come up with novel findings in chemotherapy drugs and immune modulator to control development of keloid. For these reasons, establishment of reliable animal model of keloids is very important.In this new model using an immunocompetent animal as a humanized-xenografts model, human keloid scar has been maintained for as long as 4 months. Results of migration assay have demonstrated that typical morphology of keloid fibroblast was preserved based on multiple time point observations despite its aging change. Quantitative real time polymerase chain reaction findings suggested that after implantation, there has been significant increase of vascular endothelial growth factor, CD34, and transforming growth factor beta 1 expression despite insignificant changes of hypoxia inducible factor 1 an matrix metallopeptidase 1, and matrix metallopeptidase 9 gene expression. These findings suggested that implantation of keloids within the immunocompetent animals yields is very useful experimental model in terms of fibrosis.In summary, the authors have successfully established and propagated patient-derived keloid model using the immunocompetent animals. This model could be used to test novel materials as well as combination therapies and is superior to the conventional cell line experiment models. In addition, the biology of the keloids can easily be assessed to identify predictive markers for responses to treatment regimens that are currently actively under research in various centers.
基于患者来源肿瘤异种移植的临床前模型的最新进展为许多临床领域带来了新的见解。根据我们的文献综述，许多作者认为，应使用免疫缺陷动物，如无胸腺大鼠和小鼠，以防止急性排斥反应导致的组织损失，从而建立患者来源肿瘤异种移植模型。然而，最近的进展表明，微环境作为导致疾病进展的重要因素已受到关注。此外，研究人员试图在化疗药物和免疫调节剂方面取得新的发现，以控制瘢痕疙瘩的发展。因此，建立可靠的瘢痕疙瘩动物模型非常重要。在这个使用免疫健全动物作为人源化异种移植模型的新模型中，人瘢痕疙瘩已维持长达4个月。迁移试验结果表明，尽管瘢痕疙瘩成纤维细胞存在老化变化，但基于多个时间点观察，其典型形态得以保留。定量实时聚合酶链反应结果表明，植入后，血管内皮生长因子、CD34和转化生长因子β1的表达显著增加，而缺氧诱导因子1、基质金属蛋白酶1和基质金属蛋白酶9基因表达变化不显著。这些发现表明，在免疫健全动物体内植入瘢痕疙瘩在纤维化方面是非常有用的实验模型。总之，作者成功地使用免疫健全动物建立并繁殖了患者来源的瘢痕疙瘩模型。该模型可用于测试新型材料以及联合疗法，且优于传统的细胞系实验模型。此外，瘢痕疙瘩的生物学特性可以很容易地进行评估，以识别目前各中心正在积极研究的治疗方案反应预测标志物。
