Maintenance of Primary Human Colorectal Cancer Microenvironment Using a Perfusion Bioreactor‐Based 3D Culture System

Abstract

Immunotherapy has emerged during the past two decades as an innovative and successful form of cancer treatment. However, frequently, mechanisms of actions are still unclear, predictive markers are insufficiently characterized, and preclinical assays for innovative treatments are poorly reliable. In this context, the analysis of tumor/immune system interaction plays key roles, but may be unreliably mirrored by in vivo experimental models and standard bidimensional culture systems. Tridimensional cultures of tumor cells have been developed to bridge the gap between in vitro and in vivo systems. Interestingly, defined aspects of the interaction of cells from adaptive and innate immune systems and tumor cells may also be mirrored by 3D cultures. Here we review in vitro models of cancer/immune cell interaction and we propose that updated technologies might help develop innovative treatments, identify biologicals of potential clinical relevance, and select patients eligible for immunotherapy treatments.

Addressing Patient Specificity in the Engineering of Tumor Models

“…(G) Image of glioblastoma TICs harvested from the bioreactor on day 10. (A–G) reproduced with permission from Belloni et al (2018), Manfredonia et al (2019) and Li et al (2018b), respectively. # P < 0.05.…”

“…Physical bioreactors include roller tuber, spinner flask, gyratory shakes, and microgravity bioreactors (Saglam-Metiner et al, 2019) or obtain shear via perfusion systems, with the general purpose of increasing fluid transfer by convection, ultimately improving mass transfer (Selden et al, 2018). In the context of patient-derived 3D models, both RCCS and perfusion systems were used in the field of multiple myeloma (Ferrarini et al, 2013; Belloni et al, 2018), breast cancer (Muraro et al, 2017), colorectal cancer (Manfredonia et al, 2019), and glioblastoma (Li et al, 2018b), overall enhancing the viability of the culture systems.…”

“…The maintenance of explants for up to 2 weeks enabled the assessment of anti-estrogen treatments and other antibody treatments. Subsequently, the same perfusion bioreactor concept (Figure 7B) was used to culture tumor fragments from colorectal cancer specimens, a cancer known to be more difficult to culture in vitro (Manfredonia et al, 2019). Contrary to the breast cancer study, the colorectal samples were cultured for only 3 days with the bioreactor.…”

Perfusion-Based Bioreactor Culture and Isothermal Microcalorimetry for Preclinical Drug Testing with the Carbonic Anhydrase Inhibitor SLC-0111 in Patient-Derived Neuroblastoma

“…Formerly, perfusion-based cell cultures have demonstrated a unique ability to generate tissue constructs displaying biological and structural characteristics comparable with those of primary tissues [ 13 , 14 ]. More recently, the perfusion bioreactor has proved helpful for a mid-term culture of human breast and colorectal cancer tissues [ 15 , 16 ].…”

Distribution of Particles in Human Stem Cell-Derived 3D Neuronal Cell Models: Effect of Particle Size, Charge, and Density

“…11 Previously available 2D models used for pre-clinical drug screening lack features such as the extracellular matrix (ECM), enhanced cell-to-cell contact, hypoxia and necrosis present in the in vivo tumours. [12][13][14] Therefore, inadequate in vitro models can often lead to the poor clinical outcome of initially promising nanoformulations. 15 Drug development in the neuroscience field has also suffered from the lack of appropriate in vitro models, hence there is a need for more advanced in vitro cell models for the development of therapies aimed at neurodegenerative diseases.…”