A microfluidic platform for chemoresistive testing of multicellular pleural cancer spheroids

Abstract

This study reports on a microfluidic platform on which single multicellular spheroids from malignant pleural mesothelioma (MPM), an aggressive tumor with poor prognosis, can be loaded, trapped and tested for chemotherapeutic drug response. A new method to detect the spheroid viability cultured on the microfluidic chip as a function of the drug concentration is presented. This approach is based on the evaluation of the caspase activity in the supernatant sampled from the chip and tested using a microplate reader. This simple and time-saving method does only require a minimum amount of manipulations and was established for very low numbers of cells. This feature is particularly important in view of personalised medicine applications for which the number of cells obtained from the patients is low. MPM spheroids were continuously perfused for 48 hours with cisplatin, one of the standard chemotherapeutic drugs used to treat MPM. The 50% growth inhibitory concentration of cisplatin in perfused MPM spheroids was found to be twice as high as in spheroids cultured under static conditions. This chemoresistance increase might be due to the continuous support of nutrients and oxygen to the perfused spheroids.

Reconfigurable microfluidic hanging drop network for multi-tissue interaction and analysis

“…Therefore, we believe that interconnected hanging drop networks more closely resemble the conditions in a living organ or organism and have the potential to generate more representative results. Finally, the presented technology enables the realization of more complex MT systems, featuring a larger number of different tissue types (42), and enables to simulate a continuous physiological liquid exchange-similar to that between the organs of a body-for all those tissue types.…”

“…Owing to their relatively simple formation in hanging drops, spherical MTs have been a popular choice as developmental models for several organs [31][32][33][34][35][36][37][38] . Recently, spheroids have also been formed and characterized inside microfluidic systems 25,[39][40][41] or transferred to those after external MT formation 42 . A major challenge arises from the presence of solid surfaces, to which cells tend to adhere, which, in turn, compromises reliable spheroid formation and cultivation.…”

Inventions and Innovations in Preclinical Platforms for Cancer Research

“…The similarities between in vivo tumour microenvironment and the tumour spheroids extend further. For instance, the cell proliferation activity in 3D spheroids of malignant pleural mesothelioma is more similar to that in biopsied cells [15]. Several studies illustrated that gene expressions were altered in 2D monolayer cancer cell cultures while results obtained from spheroids captured the in vivo tumour tissue expressions [16] partly as a result of higher production of the cell adhesion molecules such as E-cadherin.…”

Microfluidic Tumor-mimicking In Vitro Cell Culture Methods

“…[22][23][24][25] As shown in Fig.4a, Ruppen et al developed a spheroid trapping device which used flow resistance difference to trap individual cancer spheroids in a microchannel for chemodrug resistance testing. [26] The same group used a microfluidic channel device to form cell spheroids from single cells (Fig.4b). They compared the chemosensitivity on primary lung adenocarcinoma epithelial cells (PLETCs)-formed spheroids to that of spheroids formed from PLETCs and primary pericytes (PCs) co-culture.…”