A 3D-Bioprinted Multiple Myeloma Model. 2022

Di Wu, and Zongyi Wang, and Jun Li, and Yan Song, and Manuel Everardo Mondragon Perez, and Zixuan Wang, and Xia Cao, and Changliang Cao, and Sushila Maharjan, and Kenneth C Anderson, and Dharminder Chauhan, and Yu Shrike Zhang
Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA, 02139, USA.

Multiple myeloma (MM) is a malignancy of plasma cells accounting for ≈12% of hematological malignancies. In this study, the fabrication of a high-content in vitro MM model using a coaxial extrusion bioprinting method is reported, allowing formation of a human bone marrow-like microenvironment featuring an outer mineral-containing sheath and the inner soft hydrogel-based core. MM cells are mono-cultured or co-cultured with HS5 stromal cells that can release interleukin-6 (IL-6), where the cells show superior behaviors and responses to bortezomib in 3D models than in the planar cultures. Tocilizumab, a recombinant humanized anti-IL-6 receptor (IL-6R), is investigated for its efficacy to enhance the chemosensitivity of bortezomib on MM cells cultured in the 3D model by inhibiting IL-6R. More excitingly, in a proof-of-concept demonstration, it is revealed that patient-derived MM cells can be maintained in 3D-bioprinted microenvironment with decent viability for up to 7 days evaluated, whereas they completely die off in planar culture as soon as 5 days. In conclusion, a 3D-bioprinted MM model is fabricated to emulate some characteristics of the human bone marrow to promote growth and proliferation of the encapsulated MM cells, providing new insights for MM modeling, drug development, and personalized therapy in the future.

UI MeSH Term Description Entries
D009101 Multiple Myeloma A malignancy of mature PLASMA CELLS engaging in monoclonal immunoglobulin production. It is characterized by hyperglobulinemia, excess Bence-Jones proteins (free monoclonal IMMUNOGLOBULIN LIGHT CHAINS) in the urine, skeletal destruction, bone pain, and fractures. Other features include ANEMIA; HYPERCALCEMIA; and RENAL INSUFFICIENCY. Myeloma, Plasma-Cell,Kahler Disease,Myeloma, Multiple,Myeloma-Multiple,Myelomatosis,Plasma Cell Myeloma,Cell Myeloma, Plasma,Cell Myelomas, Plasma,Disease, Kahler,Multiple Myelomas,Myeloma Multiple,Myeloma, Plasma Cell,Myeloma-Multiples,Myelomas, Multiple,Myelomas, Plasma Cell,Myelomas, Plasma-Cell,Myelomatoses,Plasma Cell Myelomas,Plasma-Cell Myeloma,Plasma-Cell Myelomas
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000069286 Bortezomib A pyrazine and boronic acid derivative that functions as a reversible PROTEASOME INHIBITOR. It is used as an ANTINEOPLASTIC AGENT in the treatment of MULTIPLE MYELOMA and MANTLE CELL LYMPHOMA. LDP-341,PS 341,PS-341,Velcade,341, PS,LDP 341,LDP341,PS341
D059016 Tumor Microenvironment The milieu surrounding neoplasms consisting of cells, vessels, soluble factors, and molecules, that can influence and be influenced by, the neoplasm's growth. Cancer Microenvironment,Cancer Microenvironments,Microenvironment, Cancer,Microenvironment, Tumor,Microenvironments, Cancer,Microenvironments, Tumor,Tumor Microenvironments
D062028 Bioprinting A material transfer technique used for assembling biological material or cells into a prescribed organization to create functional structures such as MICROCHIP ANALYTICAL DEVICES, cell microarrays, or three dimensional anatomical structures. 3D Bioprinting,Three-Dimensional Bioprinting,3D Bioprintings,Bioprinting, 3D,Bioprinting, Three-Dimensional,Three Dimensional Bioprinting,Three-Dimensional Bioprintings
D018920 Coculture Techniques A technique of culturing mixed cell types in vitro to allow their synergistic or antagonistic interactions, such as on CELL DIFFERENTIATION or APOPTOSIS. Coculture can be of different types of cells, tissues, or organs from normal or disease states. Cocultivation,Co-culture,Coculture,Co culture,Co-cultures,Cocultivations,Coculture Technique,Cocultures
D020100 Hydrogels Water swollen, rigid, 3-dimensional network of cross-linked, hydrophilic macromolecules, 20-95% water. They are used in paints, printing inks, foodstuffs, pharmaceuticals, and cosmetics. (Grant & Hackh's Chemical Dictionary, 5th ed) Hydrogel,In Situ Hydrogel,In Situ Hydrogels,Patterned Hydrogel,Patterned Hydrogels,Hydrogel, In Situ,Hydrogel, Patterned
D023822 Tissue Engineering Generating tissue in vitro for clinical applications, such as replacing wounded tissues or impaired organs. The use of TISSUE SCAFFOLDING enables the generation of complex multi-layered tissues and tissue structures. Engineering, Tissue
D066330 Printing, Three-Dimensional Process for making, building or constructing a physical object from a three-dimensional digital model by laying down many successive thin layers of building material. 3-D Printing,3-Dimensional Printing,3D Printing,Three-Dimensional Printing,3 D Printing,3 Dimensional Printing,3-D Printings,3-Dimensional Printings,3D Printings,Printing, 3-D,Printing, 3-Dimensional,Printing, 3D,Printing, Three Dimensional,Printings, 3-D,Printings, 3-Dimensional,Printings, 3D,Printings, Three-Dimensional,Three Dimensional Printing,Three-Dimensional Printings

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