Vijaya Kumar Archana, Donate Carmen, Imhof Beat A, Matthes Thomas
Department of Pathology and Immunology, University of Geneva; Hematology Service, University Hospital, Geneva.
Hematology Service, University Hospital, Geneva.
J Vis Exp. 2018 Mar 30(133):56023. doi: 10.3791/56023.
B lymphocytes are key players in immune cell circulation and they mainly home to and reside in lymphoid organs. While normal B cells only proliferate when stimulated by T lymphocytes, oncogenic B cells survive and expand autonomously in undefined organ niches. Mantle cell lymphoma (MCL) is one such B cell disorder, where the median survival rate of patients is 4 - 5 years. This calls for the need of effective mechanisms by which the homing and engraftment of these cells are blocked in order to increase the survival and longevity of patients. Therefore, the effort to develop a xenograft mouse model to study the efficacy of MCL therapeutics by blocking the homing mechanism in vivo is of utmost importance. Development of animal recipients for human cell xenotransplantation to test early stage drugs have long been pursued, as relevant preclinical mouse models are crucial to screen new therapeutic agents. This animal model is developed to avoid human graft rejection and to establish a model for human diseases, and it may be an extremely useful tool to study disease progression of different lymphoma types and to perform preclinical testing of candidate drugs for hematologic malignancies, like MCL. We established a xenograft mouse model that will serve as an excellent resource to study and develop novel therapeutic approaches for MCL.
B淋巴细胞是免疫细胞循环中的关键参与者，它们主要归巢并驻留在淋巴器官中。正常B细胞仅在受到T淋巴细胞刺激时才增殖，而成瘤性B细胞在未明确的器官微环境中自主存活并扩增。套细胞淋巴瘤（MCL）就是这样一种B细胞疾病，患者的中位生存期为4至5年。这就需要有有效的机制来阻断这些细胞的归巢和植入，以提高患者的生存率和寿命。因此，开发一种异种移植小鼠模型来研究通过体内阻断归巢机制治疗MCL的疗效至关重要。长期以来，人们一直在努力开发用于人类细胞异种移植以测试早期药物的动物受体，因为相关的临床前小鼠模型对于筛选新的治疗药物至关重要。开发这种动物模型是为了避免人类移植物排斥反应并建立人类疾病模型，它可能是研究不同淋巴瘤类型的疾病进展以及对血液系统恶性肿瘤（如MCL）的候选药物进行临床前测试的极其有用的工具。我们建立了一种异种移植小鼠模型，它将成为研究和开发MCL新治疗方法的优秀资源。
