In the ever-evolving field of microfluidics, researchers are continually pushing the boundaries to understand complex biological phenomena. One such groundbreaking study, recently published, delves deep into the intricate pathways of multiple myeloma (MM) cancer cells within the bone marrow using a meticulously engineered microfluidic chip.
This novel microfluidic device is designed to mimic the sinusoidal niche of bone marrow, offering unprecedented insights into the trafficking of MM cells. It replicates key physiological features, including sinusoidal circulation, endothelium, and stroma, providing a realistic environment for studying the spatiotemporal interactions between MM cells and their microenvironments.
The device, based on a 96-well plate configuration, is operated inside an incubator, utilizing an external peristaltic pump. It is crafted to simulate the sinusoidal niche of bone marrow, incorporating major physiological features essential for a comprehensive study. The sinusoidal circulation is mimicked using a peristaltic pump and an external medium reservoir, ensuring a uniform shear stress distribution along the sinusoid chamber.
The microfabrication of the microfluidic chip was a meticulous process that involved established microfabrication techniques. A bubble trap was incorporated to mitigate the introduction of bubbles due to the high-velocity flow of the culture medium. A transparent polyester (PETE) membrane was strategically placed between the sinusoid and stroma chambers. This membrane served a dual purpose – providing mechanical support and offering a surface for endothelial cell adhesion and growth.
The COMSOL Multiphysics 5.3 software played a pivotal role in computing the velocity profiles and shear stress distribution in the sinusoid chamber. This simulation was crucial to ensure a uniform shear stress distribution, replicating the physiological conditions of the bone marrow’s sinusoidal niche accurately. The wall shear stress was maintained at 0.94 Pa, a parameter essential for the realistic movement and behavior of MM cells within the device.
The COMSOL Multiphysics 5.3 software played a pivotal role in computing the velocity profiles and shear stress distribution in the sinusoid chamber. This simulation was crucial to ensure a uniform shear stress distribution, replicating the physiological conditions of the bone marrow’s sinusoidal niche accurately. The wall shear stress was maintained at 0.94 Pa, a parameter essential for the realistic movement and behavior of MM cells within the device.
The tissue construction involved the seeding of the EA.hy926 cell line in the sinusoid chamber at a cell density of 5 x 10^6 cells/mL. The stroma chamber was infused with a BMSC-collagen mixture. The collagen provided the necessary stiffness to support the stromal cells during the 3D culture, ensuring the structural integrity and physiological relevance of the model.
The egression of MM cells, mediated by CXCL12, was meticulously observed. This process resulted in less organized and loosely connected ECs. Researchers noted the widening of EC junction pores and increased permeability through ECs, insights that are pivotal for understanding the complex dynamics of MM cell trafficking within the bone marrow.
The device, operated inside an incubator, was connected to an external peristaltic pump. This setup ensured the continuous and controlled flow of the culture medium, mimicking the sinusoidal circulation effectively. Real-time monitoring was facilitated by the device’s design, allowing for in-depth analysis and observations of cellular interactions and behaviors.
“Microfluidic culture device designed to mimic the trafficking of cancer cells through the sinusoidal niche of bone marrow (BM). (a) Schematic illustration of major physiological features of the sinusoidal niche. (b) Schematic illustration of the recapitulated sinusoidal niche in the device. (c) Device design based on a 96-well plate configuration. (d) Actual device operated inside an incubator using an external peristaltic pump.” Reproduced under Creative Commons Attribution 4.0 International License from Sui, C., Zilberberg, J. & Lee, W. Microfluidic device engineered to study the trafficking of multiple myeloma cancer cells through the sinusoidal niche of bone marrow. Sci Rep 12, 1439 (2022).
This innovative microfluidic device stands as a testament to the advancements in microfabrication and microfluidics. It not only offers a platform for in-depth studies on the trafficking of MM cells through the bone marrow’s sinusoidal niche but also opens doors for further research in cancer biology and drug development. The integration of microfluidic devices in studying complex cellular interactions is indeed a leap forward, promising a future where understanding and treating conditions like MM is within reach.
Figures and the abstract are reproduced from Sui, C., Zilberberg, J. & Lee, W. Microfluidic device engineered to study the trafficking of multiple myeloma cancer cells through the sinusoidal niche of bone marrow. Sci Rep 12, 1439 (2022). https://doi.org/10.1038/s41598-022-05520-4 under Creative Commons Attribution 4.0 International License
Read the original article: Microfluidic device engineered to study the trafficking of multiple myeloma cancer cells through the sinusoidal niche of bone marrow
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