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All-human microphysical model of metastasis therapy

Wheeler, SE and Borenstein, JT and Clark, AM and Ebrahimkhani, M and Fox, IJ and Griffith, L and Inman, W and Lauffenburger, D and Nguyen, T and Pillai, VC and Prantil-Baun, R and Stolz, DB and Taylor, D and Ulrich, T and Venkataramanan, R and Wells, A and Young, C (2013) All-human microphysical model of metastasis therapy. Stem Cell Research and Therapy, 4 (SUPPL.).

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Abstract

The vast majority of cancer mortalities result from distant metastases. The metastatic microenvironment provides unique protection to ectopic tumors as the primary tumors often respond to specific agents. Although significant interventional progress has been made on primary tumors, the lack of relevant accessible model in vitro systems in which to study metastases has plagued metastatic therapeutic development - particularly among micrometastases. A real-time, all-human model of metastatic seeding and cancer cells that recapitulate metastatic growth and can be probed in real time by a variety of measures and challenges would provide a critical window into the pathophysiology of metastasis and pharmacology of metastatic tumor resistance. To achieve this we are advancing our microscale bioreactor that incorporates human hepatocytes, human nonparenchymal liver cells, and human breast cancer cells to mimic the hepatic niche in three dimensions with functional tissue. This bioreactor is instrumented with oxygen sensors, micropumps capable of generating diurnally varying profiles of nutrients and hormones, while enabling real-time sampling. Since the liver is a major metastatic site for a wide variety of carcinomas and other tumors, this bioreactor uniquely allows us to more accurately recreate the human metastatic microenvironment and probe the paracrine effects between the liver parenchyma and metastatic cells. Further, as the liver is the principal site of xenobiotic metabolism, this reactor will help us investigate the chemotherapeutic response within a metabolically challenged liver microenvironment. This model is anticipated to yield markers of metastatic behavior and pharmacologic metabolism that will enable better clinical monitoring, and will guide the design of clinical studies to understand drug efficacy and safety in cancer therapeutics. This highly instrumented bioreactor format, hosting a growing tumor within a microenvironment and monitoring its responses, is readily transferable to other organs, giving this work impact beyond the liver. © 2013 BioMed Central Ltd.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Wheeler, SE
Borenstein, JT
Clark, AMAMC235@pitt.eduAMC235
Ebrahimkhani, M
Fox, IJijf5@pitt.eduIJF5
Griffith, L
Inman, W
Lauffenburger, D
Nguyen, T
Pillai, VC
Prantil-Baun, R
Stolz, DBdonna.stolz@pitt.eduDSTOLZ
Taylor, Ddtaylor@scivelo.pitt.eduDPT9
Ulrich, T
Venkataramanan, Rrv@pitt.eduRV
Wells, Aahw6@pitt.eduAHW6
Young, C
Centers: Other Centers, Institutes, or Units > McGowan Institute for Regenerative Medicine
Date: 20 December 2013
Date Type: Publication
Journal or Publication Title: Stem Cell Research and Therapy
Volume: 4
Number: SUPPL.
DOI or Unique Handle: 10.1186/scrt372
Schools and Programs: School of Medicine > Cell Biology
School of Medicine > Pathology
School of Medicine > Surgery
School of Pharmacy > Pharmaceutical Sciences
Swanson School of Engineering > Bioengineering
Refereed: Yes
Article Type: Review
Date Deposited: 02 Dec 2016 20:17
Last Modified: 11 Sep 2019 12:55
URI: http://d-scholarship.pitt.edu/id/eprint/29627

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