MICROFLUIDIC APPROACH FOR THE DEVELOPMENT OF A THREE-DIMENSIONAL BONE MARROW MICR


Year of Award:
2014
Award Type:
R21
Project Number:
CA174543
RFA Number:
RFA-CA-13-003
Technology Track:
Biospecimen Science Technologies
PI/Project Leader:
ZILBERBERG, JENNY
Other PI or Project Leader:
LEE, WOO YOUNG
Institution:
HACKENSACK UNIVERSITY MEDICAL CENTER
Multiple myeloma (MM), an incurable B cell malignancy, is the second most frequent blood disease in the United States. This disease is characterized by a clonal proliferation of malignant plasma cells in the bone marrow (BM), the presence of high levels of monoclonal serum antibody, and the development of bone lesions. Despite the introduction of a number of novel treatments MM patients still are confronted with an average survival time of 3-4 years. As opposed to other hematological malignancies, MM strongly interacts with the BM microenvironment. These interactions are responsible for the specific homing of MM cells to the BM, their proliferation and survival, the resistance of MM cellsto drug treatment, and the development of bone disease. Unfortunately, because of the challenges associated with reproducing this complex tumor niche, primary MM tumor cells have been difficult to propagate ex vivo, hampering not only the study of this cancer but the development of technologies that could facilitate personalized treatment strategies in the clinic. To address this void, we propose to develop a physiological and robust technology for better preserving the BM/MM interactions by customizing a 3D bone tissue-like scaffold microfluidic system originally designed at Stevens Institute of Technology to optimize biomaterials for orthopedic implant-related wound-healing. This system will be used as the initial working frame in the current proposal to achieve following specific aims: I) Develop an off-the- shelf technologythat enables reconstruction of BM microenvironmental factors regulating survival and proliferation of MM tumor cells present in BM biospecimens. II) Evaluate the utility of the BM biospecimen 3D culturing platform to assess drug treatment strategies for MM. From a clinical perspective, the proposed off-the-shelf microfluidic technology should: 1) maximize sample use by requiring very small amounts of patient BM cells (