The overall goal of this project is to optimize and deploy a bioengineered implant to increase the apparent space for transplanted hematopoietic stem cells during states of marrow failure. The project specific aims are: (1) Identify critical manufacturing parameters of the implant. (2) Design a clinical protocol for use of implants to rescue bone marrow failure, and (3) Image-guided monitoring of the implant therapy. Our expected contribution is the development of a novel bioengineered bone marrow patch that is significant because the protocols developed here could rescue thousands of patients who die from marrow failure by making marrow transplantation more efficient.
We have developed stromal cell-laden 3D microfabricated biomaterials (referred to as patches) that mimic the hematopoietic inductive microenvironment of the bone marrow. We now plan to evaluate the implantation of these patches as an approach to increase the effective space for hematopoietic stem cell engraftment during marrow failure. The creation, therapeutic testing, and monitoring of patch therapy is proposed to translate pre-clinical studies towards human trials.
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|Lee, Jungwoo; Heckl, Dirk; Parekkadan, Biju (2016) Multiple genetically engineered humanized microenvironments in a single mouse. Biomater Res 20:19|
|Lee, Jungwoo; Kohl, Nathaniel; Shanbhang, Sachin et al. (2015) Scaffold-integrated microchips for end-to-end in vitro tumor cell attachment and xenograft formation. Technology (Singap World Sci) 3:179-188|
|Fletcher, Anne L; Elman, Jessica S; Astarita, Jillian et al. (2014) Lymph node fibroblastic reticular cell transplants show robust therapeutic efficacy in high-mortality murine sepsis. Sci Transl Med 6:249ra109|
|Milwid, Jack M; Elman, Jessica S; Li, Matthew et al. (2014) Enriched protein screening of human bone marrow mesenchymal stromal cell secretions reveals MFAP5 and PENK as novel IL-10 modulators. Mol Ther 22:999-1007|
|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|
|Shen, Keyue; Luk, Samantha; Hicks, Daniel F et al. (2014) Resolving cancer-stroma interfacial signalling and interventions with micropatterned tumour-stromal assays. Nat Commun 5:5662|
|Elman, Jessica S; Murray, Ryan C; Murray, Ryan M et al. (2014) Pharmacokinetics of natural and engineered secreted factors delivered by mesenchymal stromal cells. PLoS One 9:e89882|
|Elman, Jessica S; Li, Matthew; Wang, Fangjing et al. (2014) A comparison of adipose and bone marrow-derived mesenchymal stromal cell secreted factors in the treatment of systemic inflammation. J Inflamm (Lond) 11:1|
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