A Coculture Based, 3D Bioprinted Ovarian Tumor Model Combining Cancer Cells and Cancer Associated Fibroblasts

Abstract

Ovarian cancer remains a major public health issue due to its poor prognosis. To develop more effective therapies, it is crucial to set‐up reliable models that closely mimic the complexity of the ovarian tumor's microenvironment. 3D bioprinting is currently a promising approach to build heterogenous and reproducible cancer models with controlled shape and architecture. However, this technology is still poorly investigated to model ovarian tumors. In this study, a 3D bioprinted ovarian tumor model combining cancer cells (SKOV‐3) and cancer associated fibroblasts (CAFs) are described. The resulting tumor models show their ability to maintain cell viability and proliferation. Cells are observed to self‐assemble in heterotypic aggregates. Moreover, CAFs are observed to be recruited and to circle cancer cells reproducing an in vivo process taking place in the tumor microenvironment. Interestingly, this approach also shows its ability to rapidly generate a high number of reproducible tumor models that can be subjected to usual characterizations (cell viability and metabolic activity; histology and immunological studies; and real‐time imaging). Therefore, these ovarian tumor models can be an interesting tool for high throughput drug screening applications.

Key aspects for conception and construction of co-culture models of tumor-stroma interactions

“…There are already 3D bioprinted systems to recapitulate vascular-like tubes (Yu et al, 2013), artificial skin (Lee et al, 2014), lung (Murphy and Atala, 2014;Marrazzo et al, 2016), kidney (Lawlor et al, 2020), cartilage (Cui et al, 2012) and brain (Han and Hsu, 2017). Indeed, cancer specific bioprinted models exist for breast (Wang et al, 2018), brain (Heinrich et al, 2019), ovarian (Baka et al, 2022) and skin (Browning et al, 2020) cancers, among others.…”

The third dimension of tumor microenvironment—The importance of tumor stroma in 3D cancer models

“…The 3DBPO model showed significant changes in cell cycle, metabolism, adherens junctions, and other pathways associated with epigenetic regulation and was also more sensitive to therapies targeted to the autophagy pathway. 113 Currently, the studies involving 3D bioprinted tumor models are trending massively, as evidenced by the great number of works reporting the preparation of 3D models of various malignancies such as malignant melanoma, 114 multiple myeloma, 115 ovarian cancer, 116 brain tumor, 117 breast cancer, 118 and urological carcinomas. 119 Three-dimensional bioprinting techniques can also be used to study the metastatic process.…”

Adipose Tissue in Breast Cancer Microphysiological Models to Capture Human Diversity in Preclinical Models

“…However, with advancements in 3D bioprinting (3DBP) technology, more customizable, comprehensive models have been developed, including systems mimicking vascular-like tubes, artificial skin, lung, kidney, cartilage, and brain [ 35 ]. Bioprinted models simulating breast, brain, ovarian, and skin cancers have been optimized over the past five years [ 2 , 81 , 82 , 83 , 84 , 85 ]. Bioprinting can be described as a process that deposits materials by layering to generate a three-dimensional structure.…”