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.
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