Bioreactor-engineered cancer tissue-like structures mimic phenotypes, gene expression profiles and drug resistance patterns observed “in vivo”

Hirt, Christian; Papadimitropoulos, Adam; Muraro, Manuele Giuseppe; Mele, Valentina; Panopoulos, Evangelos; Cremonesi, Eleonora; Ivánek, Robert; Schultz‐Thater, Elke; Droeser, Raoul A.; Mengus, Chantal; Heberer, Michael; Oertli, Daniel; Iezzi, Giovanna; Zajac, Paul; Eppenberger‐Castori, Serenella; Tornillo, Luigi; Terracciano, Luigi; Martin, Ivan; Spagnoli, Giulio C.

doi:10.1016/j.biomaterials.2015.05.037

Cited by 56 publications

(64 citation statements)

References 46 publications

(54 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…An initial density of 100 tumor cells per hanging drop optimally allowed, for both HT29 and HCT116 cells, the development of progressively growing spheroids (Figure 1 and Supplementary Figure S1). In keeping with previous studies [15, 30, 31], tumor cells cultured in 3D structures were characterized by slow proliferation reaching a plateau at 20 days (Figure 1 and Supplementary Figure S1). …”

Section: Resultssupporting

confidence: 89%

“…These conditions, combined with cell-to-cell and cell-to-matrix interactions occurring in three-dimensional structures, do impact gene and protein expression profiles and distribution and penetration of soluble factors, including drugs, possibly resulting in poor response to treatment, as typically described in avascular tumors where a formation of necrotic areas occurs [4, 5, 26, 31]. …”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Induction of hypoxia and necrosis in multicellular tumor spheroids is associated with resistance to chemotherapy treatment

et al. 2016

Self Cite

View full text Add to dashboard Cite

Culture of cancerous cells in standard monolayer conditions poorly mirrors growth in three-dimensional architectures typically observed in a wide majority of cancers of different histological origin. Multicellular tumor spheroid (MCTS) culture models were developed to mimic these features. However, in vivo tumor growth is also characterized by the presence of ischemic and necrotic areas generated by oxygenation gradients and differential access to nutrients. Hypoxia and necrosis play key roles in tumor progression and resistance to treatment. To provide in vitro models recapitulating these events in highly controlled and standardized conditions, we have generated colorectal cancer (CRC) cell spheroids of different sizes and analyzed their gene expression profiles and sensitivity to treatment with 5FU, currently used in therapeutic protocols. Here we identify three MCTS stages, corresponding to defined spheroid sizes, characterized by normoxia, hypoxia, and hypoxia plus necrosis, respectively. Importantly, we show that MCTS including both hypoxic and necrotic areas most closely mimic gene expression profiles of in vivo-developing tumors and display the highest resistance to 5FU. Taken together, our data indicate that MCTS may mimic in vitro generation of ischemic and necrotic areas in highly standardized and controlled conditions, thereby qualifying as relevant models for drug screening purposes.

show abstract

Section: Resultssupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Induction of hypoxia and necrosis in multicellular tumor spheroids is associated with resistance to chemotherapy treatment

et al. 2016

Self Cite

View full text Add to dashboard Cite

show abstract

“…Ishikawa et al (2011) used the rotating wall vessel bioreactor for cultivating 3D hepatic-like tissues for the purpose of drug testing, and showed the formation of bile duct-like structures and blood vessels from fetal liver cells. More recently, Hirt et al (2015) had shown that perfused 3D cancer tissues growth within bioreactors shared functional similarities and drug response with in vivo cancers.…”

Section: Bioreactors In Drug Discovery and Implant Testingmentioning

confidence: 99%

“…More recently, Hirt et al . () had shown that perfused 3D cancer tissues growth within bioreactors shared functional similarities and drug response with in vivo cancers.…”

Section: Introductionmentioning

confidence: 99%

Review: bioreactor design towards generation of relevant engineered tissues: focus on clinical translation

Ravichandran

Liu

Teoh

2017

J Tissue Eng Regen Med

View full text Add to dashboard Cite

In tissue engineering and regenerative medicine, studies that utilize 3D scaffolds for generating voluminous tissues are mostly confined in the realm of in vitro research and preclinical animal model testing. Bioreactors offer an excellent platform to grow and develop 3D tissues by providing conditions that mimic their native microenvironment. Aligning the bioreactor development process with a focus on patient care will aid in the faster translation of the bioreactor technology to clinics. In this review, we discuss the various factors involved in the design of clinically relevant bioreactors in relation to their respective applications. We explore the functional relevance of tissue grafts generated by bioreactors that have been designed to provide physiologically relevant mechanical cues on the growing tissue. The review discusses the recent trends in non-invasive sensing of the bioreactor culture conditions. It provides an insight to the current technological advancements that enable in situ, non-invasive, qualitative and quantitative evaluation of the tissue grafts grown in a bioreactor system. We summarize the emerging trends in commercial bioreactor design followed by a short discussion on the aspects that hamper the 'push' of bioreactor systems into the commercial market as well as 'pull' factors for stakeholders to embrace and adopt widespread utility of bioreactors in the clinical setting. Copyright © 2017 John Wiley & Sons, Ltd.

show abstract

“…For example, a colorectal cancer model was demostrated using a commercially available perfusion BR [81]. HT- 29 line cells were conventionally cultured in a monolayer or seeded on collagen sponges and maintained in a static 3D culture (as the control samples) or in a perfusion BR.…”

Section: Perfusion (Flow) Bioreactorsmentioning

confidence: 99%

Bioreactor-Based Tumor Tissue Engineering

Guller

Grebenyuk²,

Shekhter

et al. 2016

Acta Naturae

View full text Add to dashboard Cite

This review focuses on modeling of cancer tumors using tissue engineering technology. Tumor tissue engineering (TTE) is a new method of three-dimensional (3D) simulation of malignant neoplasms. Design and development of complex tissue engineering constructs (TECs) that include cancer cells, cell-bearing scaffolds acting as the extracellular matrix, and other components of the tumor microenvironment is at the core of this approach. Although TECs can be transplanted into laboratory animals, the specific aim of TTE is the most realistic reproduction and long-term maintenance of the simulated tumor properties in vitro for cancer biology research and for the development of new methods of diagnosis and treatment of malignant neoplasms. Successful implementation of this challenging idea depends on bioreactor technology, which will enable optimization of culture conditions and control of tumor TECs development. In this review, we analyze the most popular bioreactor types in TTE and the emerging applications.

show abstract

Bioreactor-engineered cancer tissue-like structures mimic phenotypes, gene expression profiles and drug resistance patterns observed “in vivo”

Cited by 56 publications

References 46 publications

Induction of hypoxia and necrosis in multicellular tumor spheroids is associated with resistance to chemotherapy treatment

Induction of hypoxia and necrosis in multicellular tumor spheroids is associated with resistance to chemotherapy treatment

Review: bioreactor design towards generation of relevant engineered tissues: focus on clinical translation

Bioreactor-Based Tumor Tissue Engineering

Contact Info

Product

Resources

About