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3D tissue-engineered bone marrow as a novel model to study pathophysiology and drug resistance in multiple myeloma

Paper ID Volume ID Publish Year Pages File Format Full-Text
5544 397 2015 15 PDF Available
Title
3D tissue-engineered bone marrow as a novel model to study pathophysiology and drug resistance in multiple myeloma
Abstract

PurposeMultiple myeloma (MM) is the second most prevalent hematological malignancy and it remains incurable despite the introduction of several novel drugs. The discrepancy between preclinical and clinical outcomes can be attributed to the failure of classic two-dimensional (2D) culture models to accurately recapitulate the complex biology of MM and drug responses observed in patients. Experimental design: We developed 3D tissue engineered bone marrow (3DTEBM) cultures derived from the BM supernatant of MM patients to incorporate different BM components including MM cells, stromal cells, and endothelial cells. Distribution and growth were analyzed by confocal imaging, and cell proliferation of cell lines and primary MM cells was tested by flow cytometry. Oxygen and drug gradients were evaluated by immunohistochemistry and flow cytometry, and drug resistance was studied by flow cytometry.Results3DTEBM cultures allowed proliferation of MM cells, recapitulated their interaction with the microenvironment, recreated 3D aspects observed in the bone marrow niche (such as oxygen and drug gradients), and induced drug resistance in MM cells more than 2D or commercial 3D tissue culture systems.Conclusions3DTEBM cultures not only provide a better model for investigating the pathophysiology of MM, but also serve as a tool for drug development and screening in MM. In the future, we will use the 3DTEBM cultures for developing personalized therapeutic strategies for individual MM patients.

Keywords
Multiple myeloma; 3D; Tissue-engineering; Drug resistance; Tumor microenvironment; Culture model
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3D tissue-engineered bone marrow as a novel model to study pathophysiology and drug resistance in multiple myeloma
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 73, December 2015, Pages 70–84
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us