Multiple myeloma (MM) is one of the most common hematological malignancies worldwide, characterized by the infiltration of monoclonal plasma cells into the bone marrow and the overproduction of monoclonal immunoglobulins. Despite the availability of various treatment options, the difficulty in selecting a suitable treatment for each patient results in a dismal prognosis. Therefore, understanding the underlying disparities among MM patients and the complex interactions between MM cells and their microenvironment is crucial to developing safe and effective treatments tailored to individual patients. Traditional two-dimensional(2D) cultures and animal models lack the tissue architecture, tumor microenvironment, and interactions between cell populations, leading to discrepancies with clinical outcomes. In contrast, three-dimensional(3D) culture models can provide a microenvironment conducive to cell function, growth, and differentiation. Thus, when considering patient heterogeneity, a 3D culture model based on patient-derived samples should be established for personalized treatment. In this study, we purposed to develop a 3D culture platform utilizing a microfluidic chip containing bone, blood vessels, MM cells, and mesenchymal stem cells (MSCs) to improve the dismal prognosis of MM patients.
The microfluidic chip was designed to have media channels on both sides. After seeding MSCs inside, osteogenesis was induced for 2-3 weeks. After osteogenic induction, MM cell lines and MSCs were cultured in adjacent channels, or HUVEC cells were cultured separately, leading to the development of a MM microfluidic chip that includes the tumor microenvironment. Patient-derived MM cells and MSCs were co-cultured on the designed MM microfluidic chip, and drug responsiveness was compared. The collection of patient cells used in this study was approved by the IRB of Incheon St. Mary's Hospital of the Catholic University.
For the composition of a personalized microenvironment, osteogenesis was successfully induced from patient MSCs for 2-3 weeks, confirmed by ALP staining, and optimal conditions for co-culturing MSCs and MM cells were established, allowing for culture beyond one week. Additionally, the platform was developed to simultaneously allow the culture of HUVEC cells. The drug responsiveness of MM cells was confirmed by administering lenalidomide and Velcade into the medium. The microfluidic chip aimed to systematically replicate not only MM cells but also the tumor microenvironment, and it was developed as a patient-specific personalized platform for MM patients.
Our experimental results demonstrate that culturing MM patient cells in a microfluidic chip enables the replication of the patient's tumor microenvironment, which can be used as a personalized treatment platform to improve therapeutic efficiency for MM patients. Furthermore, this platform can be utilized as a personalized platform for various hematological malignancies.
No relevant conflicts of interest to declare.
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