Metastasis to the bone marrow is observed in a number of fatal cancers. Tumor cells preferentially migrate to the bone cavity as a function of composition of the bone marrow. We have developed a tissue engineered analogue of the bone marrow and plan to use this construct to identify the key stromal cellular components of a bone marrow metastatic niche. We propose to: 1) Develop a microfluidic platform to capture migratory tumor cells in vitro, 2) Create tumor-stroma microenvironments on-chip, and 3) In vivo comparison and treatment study of BMSC scaffolds on tumor growth. This project will provide essential training to candidate in microfluidics, imaging, and cancer biology during the K99 training period and propel him to be a successful independent investigator in the field of biomaterials and oncology as an R00 investigator at a research university.
Tumor cell metastasis is an insidious phenomenon that causes 90% of cancer-associated death and the bone marrow has been recognized as a prime and early metastatic site of numerous tumors. The objective of proposed research is to elucidate essential stromal components of bone marrow niche that are the linchpin of a tumor metastasis using engineered bone marrow tissue models. The results of this study are expected to directly improve public health by providing alternative therapeutic strategies for preventing bone marrow metastasis.
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|Bersani, Francesca; Lee, Jungwoo; Yu, Min et al. (2014) Bioengineered implantable scaffolds as a tool to study stromal-derived factors in metastatic cancer models. Cancer Res 74:7229-38|
|Shen, Keyue; Lee, Jungwoo; Yarmush, Martin L et al. (2014) Microcavity substrates casted from self-assembled microsphere monolayers for spheroid cell culture. Biomed Microdevices 16:609-15|
|Lee, Jungwoo; Wang, Jennifer B; Bersani, Francesca et al. (2013) Capture and printing of fixed stromal cell membranes for bioactive display on PDMS surfaces. Langmuir 29:10611-6|
|Milwid, Jack M; Ichimura, Takaharu; Li, Matthew et al. (2012) Secreted factors from bone marrow stromal cells upregulate IL-10 and reverse acute kidney injury. Stem Cells Int 2012:392050|
|Berendsen, Tim A; Bruinsma, Bote G; Lee, Jungwoo et al. (2012) A simplified subnormothermic machine perfusion system restores ischemically damaged liver grafts in a rat model of orthotopic liver transplantation. Transplant Res 1:6|
|Li, Matthew; Tilles, Arno W; Milwid, Jack M et al. (2012) Phenotypic and functional characterization of human bone marrow stromal cells in hollow-fibre bioreactors. J Tissue Eng Regen Med 6:369-77|
|Lee, Jungwoo; Li, Matthew; Milwid, Jack et al. (2012) Implantable microenvironments to attract hematopoietic stem/cancer cells. Proc Natl Acad Sci U S A 109:19638-43|