MicroC³: an ex vivo microfluidic cis-coculture assay to test chemosensitivity and resistance of patient multiple myeloma cells

Abstract

Chemosensitivity and resistance assays (CSRAs) aim to direct therapy based upon ex vivo response of patient tumor cells to chemotherapeutic drugs. However, successful CSRAs have yet to be developed. Here, we exposed primary CD138+ multiple myeloma (MM) cells to bortezomib, a clinical proteasome inhibitor, in microfluidic-cis-coculture (MicroC3) incorporating patient’s own CD138− tumor-companion mononuclear cells to integrate some of the patients’ own tumor microenvironment components in CSRA design. Statistical clustering techniques segregated MicroC3 responses into two groups which correctly identified all seventeen patients as either clinically responsive or non-responsive to bortezomib-containing therapies. In contrast, when the same patient MM samples were analyzed in the absence of the CD138− cells (monoculture), the tumor cell responses did not segregate into clinical response clusters. Thus, MicroC3 identified bortezomib-therapy MM patient responses making it a viable CSRA candidate toward enabling personalized therapy.

Personalized in vitro cancer models to predict therapeutic response: Challenges and a framework for improvement

“…Several groups incorporated patient stromal cells into a variety of personalized in vitro platform architectures (K. U. Kim et al, 2005; Pak et al, 2015; Ruppen et al, 2015; Z. Xu, et al, 2013; Young, et al, 2012).…”

“…Xu, et al, 2013; Young, et al, 2012). In four cases that assessed the influence of stromal cells on drug sensitivity, the authors found differences in the effective dose of primary cancer cells cultured in a monoculture compared to co-culture, highlighting the importance of integrating supportive cell types into predictive models (Pak, et al, 2015; Ruppen, et al, 2015; Z. Xu, et al, 2013; Young, et al, 2012).…”

Precision Medicine in Oncology: In Vitro Drug Sensitivity and Resistance Test (DSRT) for Selection of Personalized Anticancer Therapy

“…The problem of insufficient cell material available for DSRT can be solved by using miniaturized platforms based on technologies alternative to microtiter plates. There are numerous studies demonstrating utilization of such platforms for screening of live mammalian cells, however few of them are focused on screening of patient‐derived cells with a goal of defining appropriate therapy for cancer patients . Some examples of such studies are given below and summarized in Table .…”

Cancer-on-a-chip systems at the frontier of nanomedicine

“…Different leukemic cells also indicated different degrees of angiogenic induction, potentially because of the different amounts of angiogenic factors produced, and the sprouted endothelial cells were observed to form lumen structures, both of which could be further enhanced by co-culturing the leukemic cells with the stromal cells. In another study, bone marrow plasma cells from patients with myeloma were cultured on a microfluidic platform; chemosensitivity and resistance assays were carried out to evaluate the ex vivo responses of these primary CD138 + multiple myeloma cells to bortezomib-containing therapies [55]. …”