Patient‐derived scaffolds as a model of colorectal cancer

Parkinson, Gabrielle T.; Salerno, Simona; Ranji, Parmida; Håkansson, Joakim; Bogestål, Yalda; Wettergren, Yvonne; Ståhlberg, Anders; Lindskog, Elinor Bexe; Landberg, Göran

doi:10.1002/cam4.3668

Cited by 19 publications

(18 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, we investigated the distribution of ECM components showing that MMP9, which is involved in matrix remodeling during metastasis, was highly expressed in invading organoids. Similar approaches investigating the influence from the surrounding tumor microenvironment on primary CRC and breast cancer development were recently established using decellularized colon and breast tissue, respectively [ 28 ], [ 29 ], [ 30 ]. Therefore, this coculture model is a useful tool to mimic cancer cell attachment and invasion during PM.…”

Section: Discussionmentioning

confidence: 99%

A human ex vivo coculture model to investigate peritoneal metastasis and innovative treatment options

Mönch

Koch

Maaß

et al. 2021

Pleura and Peritoneum

View full text Add to dashboard Cite

Objectives Peritoneal metastasis (PM) is commonly observed in patients with colorectal cancer (CRC). The outcome of these patients is poor, with an average survival of only six months without therapy, which requires a better understanding of PM biology and new treatment strategies. Methods We established and characterized a human ex vivo peritoneal model to investigate the mechanisms of peritoneal seeding and possible treatment options. For this, CRC cell lines and patient-derived tumor organoids were cultured together with human peritoneum to investigate the invasion of malignant cells and the effects of local chemotherapy. Results Fresh human peritoneum was cultured for up to three weeks in a stainless steel ring system, allowing for survival of all peritoneal structures. Peritoneal cell survival was documented by light microscopy and immunohistochemical staining. Further, immunohistological characterization of the tissue revealed CD3-positive T-lymphocytes and vimentin-positive fibroblasts within the peritoneum. In addition, extracellular matrix components (collagens, matrix metalloproteinases) were localized within the tissue. Coculture with CRC cell lines and patient-derived CRC organoids revealed that cancer cells grew on the peritoneum and migrated into the tissue. Coculture with CRC cells confirmed that hyperthermal treatment at 41 °C for 90 min significantly enhanced the intracellular entry of doxorubicin. Moreover, treatment with mitomycin C under hyperthermic conditions significantly reduced the amount of cancer cells within the peritoneum. Conclusions This human ex vivo peritoneal model provides a stringent and clinically relevant platform for the investigation of PM and for further elucidation of possible treatment options.

show abstract

Section: Discussionmentioning

confidence: 99%

A human ex vivo coculture model to investigate peritoneal metastasis and innovative treatment options

Mönch

Koch

Maaß

et al. 2021

Pleura and Peritoneum

View full text Add to dashboard Cite

show abstract

“…Beyond proteomic and structural characterization of the decellularized ECM, reports showed that tumor ECM modulates IL-8 expression by HT29 cells [ 19 ] and that both HT-29 and HCT-116 cells reduced the sensitivity to 5-fluoracil when in a 3D ECM-setting [ 49 , 53 ]. In comparison with 2D cultures, HT-29 cells grown in CRC patient-derived scaffolds also displayed changes in the expression of genes and proteins related to proliferation and an increase in those concerning pluripotency and stemness [ 151 ].…”

Section: Decellularized Colorectal Cancer Matrices As Bioactive Scaffolds For Modeling the Tumor Microenvironmentmentioning

confidence: 99%

Decellularized Colorectal Cancer Matrices as Bioactive Scaffolds for Studying Tumor-Stroma Interactions

Marques-Magalhães

Cruz

Costa

et al. 2022

Cancers

View full text Add to dashboard Cite

More than a physical structure providing support to tissues, the extracellular matrix (ECM) is a complex and dynamic network of macromolecules that modulates the behavior of both cancer cells and associated stromal cells of the tumor microenvironment (TME). Over the last few years, several efforts have been made to develop new models that accurately mimic the interconnections within the TME and specifically the biomechanical and biomolecular complexity of the tumor ECM. Particularly in colorectal cancer, the ECM is highly remodeled and disorganized and constitutes a key component that affects cancer hallmarks, such as cell differentiation, proliferation, angiogenesis, invasion and metastasis. Therefore, several scaffolds produced from natural and/or synthetic polymers and ceramics have been used in 3D biomimetic strategies for colorectal cancer research. Nevertheless, decellularized ECM from colorectal tumors is a unique model that offers the maintenance of native ECM architecture and molecular composition. This review will focus on innovative and advanced 3D-based models of decellularized ECM as high-throughput strategies in colorectal cancer research that potentially fill some of the gaps between in vitro 2D and in vivo models. Our aim is to highlight the need for strategies that accurately mimic the TME for precision medicine and for studying the pathophysiology of the disease.

show abstract

“…For example, Sun et al utilized bioprinted scaffolds seeded with hepatocellular carcinoma HepG2 cell line [13] and Abbot et al utilized silk scaffold seeded with renal cell carcinoma 786-O cell line [11]. Patient-derived tissues have also been utilized as 3D tumor models by creating patient-derived scaffolds (PDS) that are obtained via decellularization of surgically resected tumors and then used as a substrate for cell line culture [38]. Parkinson et al cultured colon cancer cell line HT29 in PDSs [38].…”

Section: Combined Application Of Biomaterials and Patient-derived Can...mentioning

confidence: 99%

Combined Application of Patient-Derived Cells and Biomaterials as 3D In Vitro Tumor Models

Hasbum

Karabulut

Reyes

et al. 2022

Cancers

View full text Add to dashboard Cite

Although advances have been made in cancer therapy, cancer remains the second leading cause of death in the U.S. and Europe, and thus efforts to continue to study and discover better treatment methods are ongoing. Three-dimensional (3D) tumor models have shown advantages over bi-dimensional (2D) cultures in evaluating the efficacy of chemotherapy. This commentary aims to highlight the potential of combined application of biomaterials with patient-derived cancer cells as a 3D in vitro model for the study and treatment of cancer patients. Five studies were discussed which demonstrate and provided early evidence to create 3D models with accurate microenvironments that are comparable to in vivo tumors. To date, the use of patient-derived cells for a more personalized approach to healthcare in combination with biomaterials to create a 3D tumor is still relatively new and uncommon for application in clinics. Although highly promising, it is important to acknowledge the current limitations and challenges of developing these innovative in vitro models, including the need for biologists and laboratory technicians to become familiar with biomaterial scaffolds, and the effort for bioengineers to create easy-to-handle scaffolds for routine assessment.

show abstract

Patient‐derived scaffolds as a model of colorectal cancer

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 19 publications

References 39 publications

A human ex vivo coculture model to investigate peritoneal metastasis and innovative treatment options

A human ex vivo coculture model to investigate peritoneal metastasis and innovative treatment options

Decellularized Colorectal Cancer Matrices as Bioactive Scaffolds for Studying Tumor-Stroma Interactions

Combined Application of Patient-Derived Cells and Biomaterials as 3D In Vitro Tumor Models

Contact Info

Product

Resources

About