title: Ex Vivo Maintenance of Primary Human Multiple Myeloma Cells through the Optimization of the Osteoblastic Niche.
abstract: We previously reported a new approach for culturing difficult-to-preserve primary patient-derived multiple myeloma cells (MMC) using an osteoblast (OSB)-derived 3D tissue scaffold constructed in a perfused microfluidic environment and a culture medium supplemented with patient plasma. In the current study, we used this biomimetic model to show, for the first time, that the long-term survival of OSB is the most critical factor in maintaining the ex vivo viability and proliferative capacity of MMC. We found that the adhesion and retention of MMC to the tissue scaffold was meditated by osteoblastic N-cadherin, as one of potential mechanisms that regulate MMC-OSB interactions. However, in the presence of MMC and patient plasma, the viability and osteogenic activity of OSB became gradually compromised, and consequently MMC could not remain viable over 3 weeks. We demonstrated that the long-term survival of both OSB and MMC could be enhanced by: (1) optimizing perfusion flow rate and patient-derived plasma composition in the culture medium and (2) replenishing OSB during culture as a practical means of prolonging MMC's viability beyond several weeks. These findings were obtained using a high-throughput well plate-based perfusion device from the perspective of optimizing the ex vivo preservation of patient-derived MM biospecimens for downstream use in biological studies and chemosensitivity analyses.
authors.affiliation: Department of Chemical Engineering and Materials Science, Stevens Institute of Technology, 1 Castle Point on Hudson, Hoboken, New Jersey, 07030, United States of America.
authors.forename: Wenting
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Chemical Engineering and Materials Science, Stevens Institute of Technology, 1 Castle Point on Hudson, Hoboken, New Jersey, 07030, United States of America.
authors.forename: Yexin
authors.initials: Y
authors.lastname: Gu
authors.affiliation: Department of Chemical Engineering and Materials Science, Stevens Institute of Technology, 1 Castle Point on Hudson, Hoboken, New Jersey, 07030, United States of America.
authors.forename: Qiaoling
authors.initials: Q
authors.lastname: Sun
authors.affiliation: John Theurer Cancer Center, Hackensack University Medical Center, Hackensack, New Jersey, 07601, United States of America.
authors.forename: David S
authors.initials: DS
authors.lastname: Siegel
authors.affiliation: Department of Chemistry, Chemical Biology, and Biomedical Engineering, Stevens Institute of Technology, Hoboken, New Jersey, 07030, United States of America; Center for Healthcare Innovation, Stevens Institute of Technology, Hoboken, New Jersey, 07030, United States of America.
authors.forename: Peter
authors.initials: P
authors.lastname: Tolias
authors.affiliation: Research Department, Hackensack University Medical Center, Hackensack, New Jersey, 07601, United States of America.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Chemical Engineering and Materials Science, Stevens Institute of Technology, 1 Castle Point on Hudson, Hoboken, New Jersey, 07030, United States of America.
authors.forename: Woo Y
authors.initials: WY
authors.lastname: Lee
authors.affiliation: John Theurer Cancer Center, Hackensack University Medical Center, Hackensack, New Jersey, 07601, United States of America; Research Department, Hackensack University Medical Center, Hackensack, New Jersey, 07601, United States of America.
authors.forename: Jenny
authors.initials: J
authors.lastname: Zilberberg
mesh_terms: D015703:Antigens, CD / Q000235:genetics* / Q000378:metabolism; D015820:Cadherins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D049109:Cell Proliferation; D002470:Cell Survival; D018920:Coculture Techniques; D003470:Culture Media / Q000737:chemistry / Q000494:pharmacology; D015870:Gene Expression; D006801:Humans; D056656:Lab-On-A-Chip Devices; D009101:Multiple Myeloma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D009367:Neoplasm Staging; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D010477:Perfusion; D061251:Primary Cell Culture; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D054457:Tissue Scaffolds; D014407:Tumor Cells, Cultured
chemical_list: D015703:Antigens, CD; C050361:CDH2 protein, human; D015820:Cadherins; D003470:Culture Media; D034741:RNA, Small Interfering