SCID-hu and In Vivo Modeling

临床相关的动物模型对于剖析多发性骨髓瘤（MM）发病机制的关键方面非常重要。在过去的10年里，骨髓瘤研究和治疗研究所提供了极好的条件（例如，获得原始样品，临床和转化程序之间的长期相互作用），用于开发独特的临床相关细胞系，并用于建立SCID-hu和SCID-rab小鼠模型，其允许原发性骨髓瘤的可再现移植和典型MM表现的诱导，包括临床观察到的疾病异质性。许多用于核心D的模型和细胞系都是在核心主任（Shmuel Yaccoby博士）的帮助下开发的; Yaccoby博士和他的团队是使用这些系统研究骨髓瘤生物学和治疗的专家，并且有与项目研究人员合作的历史。Core D完全具备提供体内建模服务的能力，特别是与项目项目的特定需求相关，包括研究骨髓瘤从一个骨部位转移到另一个骨部位（项目3和4），开发骨髓瘤诱导的溶骨性骨病的疗法（项目4），移植人类免疫细胞用于免疫治疗（项目2），验证新的临床发现（项目1和2），并开发靶向治疗（所有项目）。支持体内建模实验。核心D将使用移植有原代骨髓瘤细胞（从核心B获得）或骨髓瘤细胞系（基质依赖性或非依赖性）并根据项目特定目的进行治疗的SCID-hu、SCID-raB和NOD/SCID/IL 2 ry [null]-hu小鼠模型。Core D还将为骨髓瘤细胞系在SCID小鼠中的全身、腓肠内和皮下移植提供服务。将通过测量小鼠血清中的人单克隆免疫球蛋白、活体动物生物发光成像和组织学检查（通过核心E）监测骨髓瘤生长。将通过X线、骨矿物质密度测量和组织形态计量学评估骨髓瘤骨病。提供这些重要的服务。核心D将进行该计划每个项目（目标1）提出的体内建模，并验证和开发与该计划每个项目（目标2）研究相关的分子靶点和新干预措施。动物研究是昂贵的，劳动力和时间密集型的，技术上具有挑战性;核心D将通过提供集中的设施和专家人员，为所有项目提供有效的解决方案，从而加快研究和后续临床成功的转化。 相关性（参见说明）：

Clinically relevant animal models are important for dissecting crucial aspects of multiple myeloma (MM) pathogenesis. During the past 10 years, the Myeloma Institute for Research and Therapy has provided excellent conditions (e.g., access to primary samples, long-term interactions between clinical and translational programs) for developing unique, clinically relevant cell lines and for establishing the SCID-hu and SCID-rab mouse models, which allow reproducible engraftment of primary myeloma and induction of typical MM manifestations, including clinically observed disease heterogeneity. Many of the models and cell lines proposed for use in Core D were developed with the help of the Core Director (Shmuel Yaccoby, PhD); Dr. Yaccoby and his team are experts in using these systems to study myeloma biology and therapy and have a history of collaborating with program investigators. Core D is fully equipped to provide In vivo modeling services particularly relevant to specific needs of program projects, including studying myeloma metastasis from one bone site to another (Projects 3 and 4), developing therapies for myeloma-induced osteolytic bone disease (Project 4), engrafting human immune cells for immunotherapy (Project 2), validating novel clinical findings (Projects 1 and 2), and developing targeted therapies (all projects). To support In vivo modeling experiments. Core D will use SCID-hu, SCID-rab, and N0D/SCID/lL2ry[null]-hu mouse models engrafted with primary myeloma cells (obtained from Core B) or myeloma cell lines (stroma-dependent or - independent) and treated according to project specific aims. Core D also will provide services for systemic, intrafibial, and subcutaneous engraftment of myeloma cell lines in SCID mice. Myeloma growth will be monitored by measuring human monoclonal immunoglobulins in mice sera, by live-animal bioluminescence imaging, and by histological examinations (through Core E). Myeloma bone disease will be assessed by X-rays, bone mineral density measurements, and histomorphometry. To provide these crucial services. Core D will conduct in vivo modeling proposed by each project of the program (Aim 1), and validate and develop molecular targets and novel interventions relevant to the investigations of each project of the program (Aim 2). Animal studies are expensive, labor and time intensive, and technically challenging; Core D will provide an efficient solution for all projects by providing centralized facilities with expert staffing, resulting in accelerated translation of research and subsequent clinical successes. RELEVANCE (See instructions):