Ex Vivo Maintenance of Primary Human Multiple Myeloma Cells through the Optimization of the Osteoblastic Niche
Wenting Zhang1, Yexin Gu1, Qiaoling Sun1
1Department of Chemical Engineering and Materials Science, Stevens Institute of Technology, 1 Castle Point on Hudson, Hoboken, New Jersey, 07030, United States of America.
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.
Insights
Osteoblast (OSB) survival is critical for culturing multiple myeloma cells (MMC) ex vivo. Optimizing culture conditions and replenishing OSB can extend MMC viability for research and drug testing.
Area of Science:
- Biomedical Engineering
- Hematology
- Cancer Research
Background:
- Primary patient-derived multiple myeloma cells (MMC) are challenging to culture ex vivo.
- Previous work established a 3D tissue scaffold model using osteoblasts (OSB) and patient plasma in a microfluidic system.
Purpose of the Study:
- To determine the critical factors for maintaining ex vivo viability and proliferative capacity of multiple myeloma cells (MMC).
- To investigate mechanisms regulating MMC-osteoblast (OSB) interactions within a biomimetic culture model.
- To identify strategies for enhancing the long-term survival of both MMC and OSB ex vivo.
Main Methods:
- Utilized a biomimetic model comprising an osteoblast (OSB)-derived 3D tissue scaffold in a perfused microfluidic environment.
- Employed a culture medium supplemented with patient plasma.
- Investigated the role of osteoblastic N-cadherin in MMC-OSB adhesion and retention.
- Employed a high-throughput well plate-based perfusion device for optimization.
Main Results:
- Long-term osteoblast (OSB) survival was identified as the most critical factor for maintaining ex vivo multiple myeloma cell (MMC) viability and proliferation.
- Osteoblastic N-cadherin mediates MMC adhesion and retention to the tissue scaffold.
- MMC and patient plasma compromised OSB viability and osteogenic activity, limiting MMC viability to under 3 weeks.
- Optimizing perfusion flow rate, patient plasma composition, and replenishing OSB significantly enhanced the long-term survival of both cell types.
Conclusions:
- The long-term survival of osteoblasts (OSB) is paramount for successful ex vivo culture of multiple myeloma cells (MMC).
- Strategies including optimized perfusion, plasma composition, and OSB replenishment can prolong MMC viability beyond several weeks.
- These findings improve ex vivo preservation of patient-derived MM biospecimens for downstream biological studies and chemosensitivity analyses.
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