Mesenchymal Stem Cells Relevance in Multicellular Bioengineered 3D In Vitro Tumor Models

Abstract

In vitro 3D tumor microenvironment mimicking models are gathering momentum as alternatives to traditional 2D flat monolayer cultures due to their potential for recapitulating major cancer hallmarks. To fulfill such potential, it is crucial that 3D tumor testing platforms completely emulate in vitro the complex in vivo tumor niche and its cellular constituents. Mesenchymal stem cells (MSCs) are recognized to play a pivotal multi-modulatory role in cancer, generating interest as biological targets and as key tumor suppressing, or tumor promoting effectors. This review discusses the biological influence of different types of MSCs in the tumor microenvironment and showcases recent studies that engineer 3D MSCs-cancer cells co-cultures as advanced in vitro therapy testing platforms. A special focus is given to MSCs-cancer 3D co-culture set-up parameters, challenges, and future opportunities. Understanding cancer-MSCs crosstalk and their underlying effects is envisioned to support the development of advanced 3D in vitro disease models for discovery of forefront cancer treatments.

Three‐Dimensional Osteosarcoma Models for Advancing Drug Discovery and Development

“…Moreover, cancer cells showed an osteolytic effect on bone mineralization through the reduced calcium deposition in co‐cultures, which reflects its influence in the deregulation of bone homeostasis. The posterior addition of MSCs to breast cancer cells revealed the highly discussed modulatory role of stromal cells in tumor progression, invasiveness, and angiogenicity, demonstrating its importance for advancing 3D in vitro platforms for therapy development . In this study, an anticancer drug for breast cancer, paclitaxel, was tested in the co‐culture 3D model showing a significant increase in drug resistance when compared with breast cancer monoculture (Figure A,B).…”

“…At the same time, the design of a platform for specific delivery of anticancer drugs has also been a focus, particularly in the nanomedicine field. [112] In this study, an anticancer drug for breast cancer, paclitaxel, was tested in the co-culture 3D model showing a significant increase in drug resistance when compared with breast cancer monoculture [111] (Figure 5A,B). [110] Folate conjugated fibroin nanoparticles loaded with doxorubicin were fabricated and its efficiency was evaluated in a coculture of MG-63 osteoblast-like cells with MDA-MD-231 human adenocarcinoma cell line.…”

Selective Cytotoxicity of a Novel Trp‐Rich Peptide against Lung Tumor Spheroids Encapsulated inside a 3D Microfluidic Device

“…[ 47 ] Therefore, it was important to choose MSCs as the healthy cell control to test against the anticancer peptide. The role of MSCs in tumor progression or suppression is still controversial, [ 53 ] but if they do indeed suppress tumors then this opens up the possibility of using MSC and ACP together against cancer cells without losing MSCs in the process. Furthermore, it would be interesting to investigate the effects of the ACP on other types of cells which reside in a tumor environment such as tumor‐associated fibroblasts, endothelial cells, other stem cells, and even immune cells.…”

Design of spherically structured 3D in vitro tumor models -Advances and prospects

“…The ability to restrain direct cellular contact makes microencapsulated 3D-MCTS as an ideal model to study the diverse paracrine interactions occurring in the TME between the different key cellular populations such as immune cells and mesenchymal stem cells [209]. This capacity of microencapsulated models was exploited by Yeung and co-workers [210], to study non-direct communication between neuroblastoma and bone-marrow derived mesenchymal stem cells.…”