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Sousa MGC, Brasino DSK, Krieger M, Dindar DA, Duhen R, Zhang Z, Franca CM, Bertassoni LE. Host-microbe-cancer interactions on-a-chip. Front Bioeng Biotechnol 2025; 13:1505963. [PMID: 40230461 PMCID: PMC11994592 DOI: 10.3389/fbioe.2025.1505963] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2024] [Accepted: 03/11/2025] [Indexed: 04/16/2025] Open
Abstract
The tumor microbiota has emerged as a pivotal contributor to a variety of cancers, impacting disease development, progression, and therapeutic resistance. Due to the complexity of the tumor microenvironment, reproducing the interactions between the microbes, tumor cells, and the immune system remains a great challenge for both in vitro and in vivo studies. To this end, significant progress has been made toward leveraging tumor-on-a-chip model systems to replicate critical hallmarks of the native disease in vitro. These microfluidic platforms offer the ability to mimic essential components of the tumor microenvironment, including controllable fluid flow conditions, manipulable extracellular matrix dynamics, and intricate 3D multi-cellular communication. The primary objective of this review is to discuss recent challenges and advances in engineering host-microbiota and tumor interactions on-a-chip. Ultimately, overcoming these obstacles will help us gain deeper insights into tumor-microbe interactions and enhance avenues for developing more effective cancer therapies.
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Affiliation(s)
- Mauricio G. C. Sousa
- Knight Cancer Precision Biofabrication Hub, Knight Cancer Institute, Oregon Health & Science University, Portland, OR, United States
- Cancer Early Detection Advanced Research Center, Oregon Health & Science University, Portland, OR, United States
- Department of Biomaterial and Biomedical Sciences, School of Dentistry, Oregon Health & Science University, Portland, OR, United States
| | - Danielle S. K. Brasino
- Department of Microbiology and Molecular Genetics, Robert Larner College of Medicine at the University of Vermont, Burlington, VT, United States
| | - Madeline Krieger
- Cancer Early Detection Advanced Research Center, Oregon Health & Science University, Portland, OR, United States
| | - Duygu A. Dindar
- Cancer Early Detection Advanced Research Center, Oregon Health & Science University, Portland, OR, United States
| | - Rebekka Duhen
- Knight Cancer Precision Biofabrication Hub, Knight Cancer Institute, Oregon Health & Science University, Portland, OR, United States
- Cancer Early Detection Advanced Research Center, Oregon Health & Science University, Portland, OR, United States
| | - Zhenzhen Zhang
- Division of Oncological Sciences, Oregon Health & Science University, Portland, OR, United States
| | - Cristiane Miranda Franca
- Knight Cancer Precision Biofabrication Hub, Knight Cancer Institute, Oregon Health & Science University, Portland, OR, United States
- Cancer Early Detection Advanced Research Center, Oregon Health & Science University, Portland, OR, United States
- Department of Biomaterial and Biomedical Sciences, School of Dentistry, Oregon Health & Science University, Portland, OR, United States
| | - Luiz E. Bertassoni
- Knight Cancer Precision Biofabrication Hub, Knight Cancer Institute, Oregon Health & Science University, Portland, OR, United States
- Cancer Early Detection Advanced Research Center, Oregon Health & Science University, Portland, OR, United States
- Department of Biomaterial and Biomedical Sciences, School of Dentistry, Oregon Health & Science University, Portland, OR, United States
- Division of Oncological Sciences, Oregon Health & Science University, Portland, OR, United States
- Department of Biomedical Engineering, School of Medicine, Oregon Health & Science University, Portland, OR, United States
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Li Y, Gao X, Li Y, Yan S, Zhang Y, Zheng X, Gu Q. Endocytosis: the match point of nanoparticle-based cancer therapy. J Mater Chem B 2024; 12:9435-9458. [PMID: 39192831 DOI: 10.1039/d4tb01227e] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/29/2024]
Abstract
Nanomedicine has inspired a ground-breaking strategy for cancer therapy. By intelligently assembling diverse moieties to form nanoparticles, numerous functionalities such as controlled release, synergistic efficiency, and in situ killing can be achieved. The emerging nanoparticles have been designed with elevated targeting efficiency as targeting cancer cells is the primary requirement for nanoparticles. However, effective targeting does not guarantee therapeutic effects as endocytosis is a prerequisite for nanoparticles to exert effects. The recent decade has witnessed the rapid development of endocytosis-oriented nanoparticles, and this review subtly analyzes, categorizes, and exemplifies these nanoparticles according to their biological internalization patterns, and the correlation between the endocytosis mechanism and the property of nanoparticles is bridged. Based on the interdisciplinary vision, the present challenges and future perspectives of nanoparticle design for successful endocytosis are discussed, highlighting the potential strategies for the future development of endocytosis-oriented nanoparticles, thus facilitating the endocytosis-oriented strategy from bench to bedside. The undeniable fact is that endocytosis-oriented nanoparticles will definitely bring new blood to the next generation of advanced cancer therapies.
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Affiliation(s)
- Yonglu Li
- School of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou 310018, Zhejiang, People's Republic of China.
| | - Xin Gao
- School of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou 310018, Zhejiang, People's Republic of China.
| | - Yapeng Li
- School of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou 310018, Zhejiang, People's Republic of China.
| | - Shihai Yan
- School of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou 310018, Zhejiang, People's Republic of China.
| | - Yiru Zhang
- Department of Food Science and Nutrition, Zhejiang Key Laboratory for Agro-food Processing, Fuli Institute of Food Science, National Engineering Laboratory of Intelligent Food Technology and Equipment, Zhejiang University, Hangzhou 310058, People's Republic of China
| | - Xiaodong Zheng
- Department of Food Science and Nutrition, Zhejiang Key Laboratory for Agro-food Processing, Fuli Institute of Food Science, National Engineering Laboratory of Intelligent Food Technology and Equipment, Zhejiang University, Hangzhou 310058, People's Republic of China
| | - Qing Gu
- School of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou 310018, Zhejiang, People's Republic of China.
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Saberian E, Jenča A, Petrášová A, Zare-Zardini H, Ebrahimifar M. Application of Scaffold-Based Drug Delivery in Oral Cancer Treatment: A Novel Approach. Pharmaceutics 2024; 16:802. [PMID: 38931923 PMCID: PMC11207321 DOI: 10.3390/pharmaceutics16060802] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2024] [Revised: 05/23/2024] [Accepted: 05/30/2024] [Indexed: 06/28/2024] Open
Abstract
This comprehensive review consolidates insights from two sources to emphasize the transformative impact of scaffold-based drug delivery systems in revolutionizing oral cancer therapy. By focusing on their core abilities to facilitate targeted and localized drug administration, these systems enhance therapeutic outcomes significantly. Scaffolds, notably those coated with anti-cancer agents such as cisplatin and paclitaxel, have proven effective in inhibiting oral cancer cell proliferation, establishing a promising avenue for site-specific drug delivery. The application of synthetic scaffolds, including Poly Ethylene Glycol (PEG) and poly(lactic-co-glycolic acid) (PLGA), and natural materials, like collagen or silk, in 3D systems has been pivotal for controlled release of therapeutic agents, executing diverse anti-cancer strategies. A key advancement in this field is the advent of smart scaffolds designed for sequential cancer therapy, which strive to refine drug delivery systems, minimizing surgical interventions, accentuating the significance of 3D scaffolds in oral cancer management. These systems, encompassing local drug-coated scaffolds and other scaffold-based platforms, hold the potential to transform oral cancer treatment through precise interventions, yielding improved patient outcomes. Local drug delivery via scaffolds can mitigate systemic side effects typically associated with chemotherapy, such as nausea, alopecia, infections, and gastrointestinal issues. Post-drug release, scaffolds foster a conducive environment for non-cancerous cell growth, adhering and proliferation, demonstrating restorative potential. Strategies for controlled and targeted drug delivery in oral cancer therapy span injectable self-assembling peptide hydrogels, nanocarriers, and dual drug-loaded nanofibrous scaffolds. These systems ensure prolonged release, synergistic effects, and tunable targeting, enhancing drug delivery efficiency while reducing systemic exposure. Smart scaffolds, capable of sequential drug release, transitioning to cell-friendly surfaces, and enabling combinatorial therapy, hold the promise to revolutionize treatment by delivering precise interventions and optimized outcomes. In essence, scaffold-based drug delivery systems, through their varied forms and functionalities, are reshaping oral cancer therapy. They target drug delivery efficiency, diminish side effects, and present avenues for personalization. Challenges like fabrication intricacy, biocompatibility, and scalability call for additional research. Nonetheless, the perspective on scaffold-based systems in oral cancer treatment is optimistic, as ongoing advancements aim to surmount current limitations and fully leverage their potential in cancer therapy.
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Affiliation(s)
- Elham Saberian
- Klinika and Akadémia Košice, Pavol Jozef Šafárik University, n.o. Bačíkova 7, 04001 Kosice, Slovakia;
| | - Andrej Jenča
- Klinika of Stomatology and Maxillofacial Surgery Akadémia Košice, UPJS LF, Pavol Jozef Šafárik University, n.o. Bačíkova 7, 04001 Kosice, Slovakia; (A.J.); (A.P.)
| | - Adriána Petrášová
- Klinika of Stomatology and Maxillofacial Surgery Akadémia Košice, UPJS LF, Pavol Jozef Šafárik University, n.o. Bačíkova 7, 04001 Kosice, Slovakia; (A.J.); (A.P.)
| | - Hadi Zare-Zardini
- Department of Biomedical Engineering, Meybod University, Meybod 89616-99557, Iran
| | - Meysam Ebrahimifar
- Department of Toxicity, Faculty of Pharmacy, Islamic Azad University, Shahreza Branch, Shahreza 81796-35875, Iran
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Gupta B, Malviya R, Srivastava S, Ahmad I, Rab SO, Singh DP. 3D Printed Nanosensors for Cancer Diagnosis: Advances and Future Perspective. Curr Pharm Des 2024; 30:2993-3008. [PMID: 39161144 DOI: 10.2174/0113816128322300240725052530] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2024] [Revised: 06/10/2024] [Accepted: 06/19/2024] [Indexed: 08/21/2024]
Abstract
Cancer is the leading cause of mortality worldwide, requiring continuous advancements in diagnosis and treatment. Traditional methods often lack sensitivity and specificity, leading to the need for new methods. 3D printing has emerged as a transformative tool in cancer diagnosis, offering the potential for precise and customizable nanosensors. These advancements are critical in cancer research, aiming to improve early detection and monitoring of tumors. In current times, the usage of the 3D printing technique has been more prevalent as a flexible medium for the production of accurate and adaptable nanosensors characterized by exceptional sensitivity and specificity. The study aims to enhance early cancer diagnosis and prognosis by developing advanced 3D-printed nanosensors using 3D printing technology. The research explores various 3D printing techniques, design strategies, and functionalization strategies for cancer-specific biomarkers. The integration of these nanosensors with detection modalities like fluorescence, electrochemical, and surface-enhanced Raman spectroscopy is also evaluated. The study explores the use of inkjet printing, stereolithography, and fused deposition modeling to create nanostructures with enhanced performance. It also discusses the design and functionalization methods for targeting cancer indicators. The integration of 3D-printed nanosensors with multiple detection modalities, including fluorescence, electrochemical, and surface-enhanced Raman spectroscopy, enables rapid and reliable cancer diagnosis. The results show improved sensitivity and specificity for cancer biomarkers, enabling early detection of tumor indicators and circulating cells. The study highlights the potential of 3D-printed nanosensors to transform cancer diagnosis by enabling highly sensitive and specific detection of tumor biomarkers. It signifies a pivotal step forward in cancer diagnostics, showcasing the capacity of 3D printing technology to produce advanced nanosensors that can significantly improve early cancer detection and patient outcomes.
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Affiliation(s)
- Babita Gupta
- Department of Pharmacy, School of Medical and Allied Sciences, Galgotias University, Greater Noida, U.P., India
| | - Rishabha Malviya
- Department of Pharmacy, School of Medical and Allied Sciences, Galgotias University, Greater Noida, U.P., India
| | - Saurabh Srivastava
- School of Pharmacy, KPJ Healthcare University College (KPJUC), Nilai, Malaysia
| | - Irfan Ahmad
- Department of Clinical Laboratory Sciences, College of Applied Medical Science, King Khalid University, Abha, Saudi Arabia
| | - Safia Obaidur Rab
- Department of Clinical Laboratory Sciences, College of Applied Medical Science, King Khalid University, Abha, Saudi Arabia
| | - Deependra Pratap Singh
- School of Pharmacy, Graphic Era Hill University, Dehradun, India
- Graphic Era (Deemed to be University), Clement Town, Dehradun, India
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5
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Zhang Y. 3D Printing for Cancer Diagnosis: What Unique Advantages Are Gained? ACS MATERIALS AU 2023; 3:620-635. [PMID: 38089653 PMCID: PMC10636786 DOI: 10.1021/acsmaterialsau.3c00046] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/28/2023] [Revised: 08/19/2023] [Accepted: 08/21/2023] [Indexed: 09/20/2024]
Abstract
Cancer is a complex disease with global significance, necessitating continuous advancements in diagnostics and treatment. 3D printing technology has emerged as a revolutionary tool in cancer diagnostics, offering immense potential in detection and monitoring. Traditional diagnostic methods have limitations in providing molecular and genetic tumor information that is crucial for personalized treatment decisions. Biomarkers have become invaluable in cancer diagnostics, but their detection often requires specialized facilities and resources. 3D printing technology enables the fabrication of customized sensor arrays, enhancing the detection of multiple biomarkers specific to different types of cancer. These 3D-printed arrays offer improved sensitivity, allowing the detection of low levels of biomarkers, even in complex samples. Moreover, their specificity can be fine-tuned, reducing false-positive and false-negative results. The streamlined and cost-effective fabrication process of 3D printing makes these sensor arrays accessible, potentially improving cancer diagnostics on a global scale. By harnessing 3D printing, researchers and clinicians can enhance early detection, monitor treatment response, and improve patient outcomes. The integration of 3D printing in cancer diagnostics holds significant promise for the future of personalized cancer care.
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Affiliation(s)
- Yu Zhang
- Division
of Molecular Pharmaceutics and Drug Delivery, College of Pharmacy, The University of Texas at Austin, Austin, Texas 78705, United States
- Pharmaceutics
and Drug Delivery, School of Pharmacy, The
University of Mississippi, Oxford, Mississippi 38677-1848, United States
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Arutyunyan I, Jumaniyazova E, Makarov A, Fatkhudinov T. In Vitro Models of Head and Neck Cancer: From Primitive to Most Advanced. J Pers Med 2023; 13:1575. [PMID: 38003890 PMCID: PMC10672510 DOI: 10.3390/jpm13111575] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2023] [Revised: 10/31/2023] [Accepted: 11/01/2023] [Indexed: 11/26/2023] Open
Abstract
For several decades now, researchers have been trying to answer the demand of clinical oncologists to create an ideal preclinical model of head and neck squamous cell carcinoma (HNSCC) that is accessible, reproducible, and relevant. Over the past years, the development of cellular technologies has naturally allowed us to move from primitive short-lived primary 2D cell cultures to complex patient-derived 3D models that reproduce the cellular composition, architecture, mutational, or viral load of native tumor tissue. Depending on the tasks and capabilities, a scientific laboratory can choose from several types of models: primary cell cultures, immortalized cell lines, spheroids or heterospheroids, tissue engineering models, bioprinted models, organoids, tumor explants, and histocultures. HNSCC in vitro models make it possible to screen agents with potential antitumor activity, study the contribution of the tumor microenvironment to its progression and metastasis, determine the prognostic significance of individual biomarkers (including using genetic engineering methods), study the effect of viral infection on the pathogenesis of the disease, and adjust treatment tactics for a specific patient or groups of patients. Promising experimental results have created a scientific basis for the registration of several clinical studies using HNSCC in vitro models.
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Affiliation(s)
- Irina Arutyunyan
- Research Institute of Molecular and Cellular Medicine, RUDN University, 6 Miklukho-Maklaya Street, 117198 Moscow, Russia; (I.A.); (A.M.); (T.F.)
- National Medical Research Center for Obstetrics, Gynecology and Perinatology Named after Academician V.I. Kulakov Ministry of Healthcare of the Russian Federation, 4 Oparina Street, 117997 Moscow, Russia
| | - Enar Jumaniyazova
- Research Institute of Molecular and Cellular Medicine, RUDN University, 6 Miklukho-Maklaya Street, 117198 Moscow, Russia; (I.A.); (A.M.); (T.F.)
| | - Andrey Makarov
- Research Institute of Molecular and Cellular Medicine, RUDN University, 6 Miklukho-Maklaya Street, 117198 Moscow, Russia; (I.A.); (A.M.); (T.F.)
- Histology Department, Pirogov Russian National Research Medical University, Ministry of Healthcare of the Russian Federation, 117997 Moscow, Russia
| | - Timur Fatkhudinov
- Research Institute of Molecular and Cellular Medicine, RUDN University, 6 Miklukho-Maklaya Street, 117198 Moscow, Russia; (I.A.); (A.M.); (T.F.)
- Avtsyn Research Institute of Human Morphology of Federal State Budgetary Scientific Institution Petrovsky National Research Centre of Surgery, 3 Tsyurupy Street, 117418 Moscow, Russia
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Baskar G, Palaniyandi T, Viswanathan S, Wahab MRA, Surendran H, Ravi M, Sivaji A, Rajendran BK, Natarajan S, Govindasamy G. Recent and advanced therapy for oral cancer. Biotechnol Bioeng 2023; 120:3105-3115. [PMID: 37243814 DOI: 10.1002/bit.28452] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2022] [Revised: 05/15/2023] [Accepted: 05/16/2023] [Indexed: 05/29/2023]
Abstract
Oral cancer is a common and deadly kind of tissue invasion, has a high death rate, and may induce metastasis that mostly affects adults over the age of 40. Most in vitro traditional methods for studying cancer have included the use of monolayer cell cultures and several animal models. There is a worldwide effort underway to reduce the excessive use of laboratory animals since, although being physiologically adequate, animal models rarely succeed in exactly mimicking human models. 3D culture models have gained great attention in the area of biomedicine because of their capacity to replicate parent tissue. There are many benefits to using a drug delivery approach based on nanoparticles in cancer treatment. Because of this, in vitro test methodologies are crucial for evaluating the efficacy of prospective novel nanoparticle drug delivery systems. This review discusses current advances in the utility of 3D cell culture models including multicellular spheroids, patient-derived explant cultures, organoids, xenografts, 3D bioprinting, and organoid-on-a-chip models. Aspects of nanoparticle-based drug discovery that have utilized 2D and 3D cultures for a better understanding of genes implicated in oral cancers are also included in this review.
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Affiliation(s)
- Gomathy Baskar
- Department of Biotechnology, Dr. M.G.R. Educational and Research Institute, Deemed to be University, Chennai, India
| | - Thirunavukkarasu Palaniyandi
- Department of Biotechnology, Dr. M.G.R. Educational and Research Institute, Deemed to be University, Chennai, India
- Department of Anatomy, Biomedical Research Unit and Laboratory Animal Centre, Saveetha Dental College and Hospital, SIMATS, Saveetha University, Chennai, India
| | - Sandhiya Viswanathan
- Department of Biotechnology, Dr. M.G.R. Educational and Research Institute, Deemed to be University, Chennai, India
| | - Mugip Rahaman Abdul Wahab
- Department of Biotechnology, Dr. M.G.R. Educational and Research Institute, Deemed to be University, Chennai, India
| | - Hemapreethi Surendran
- Department of Biotechnology, Dr. M.G.R. Educational and Research Institute, Deemed to be University, Chennai, India
| | - Maddaly Ravi
- Department of Human Genetics, Sri Ramachandra Institute of Higher Education and Research, Chennai, India
| | - Asha Sivaji
- Department of Biochemistry, DKM College for Women, Vellore, India
| | | | - Sudhakar Natarajan
- Department of HIV/AIDS, ICMR - National Institute for Research in Tuberculosis (NIRT), Chennai, India
| | - Gopu Govindasamy
- Department of Surgical Oncology, Rajiv Gandhi Government General Hospital and Madras Medical College, Chennai, India
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8
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Proietto M, Crippa M, Damiani C, Pasquale V, Sacco E, Vanoni M, Gilardi M. Tumor heterogeneity: preclinical models, emerging technologies, and future applications. Front Oncol 2023; 13:1164535. [PMID: 37188201 PMCID: PMC10175698 DOI: 10.3389/fonc.2023.1164535] [Citation(s) in RCA: 35] [Impact Index Per Article: 17.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2023] [Accepted: 04/11/2023] [Indexed: 05/17/2023] Open
Abstract
Heterogeneity describes the differences among cancer cells within and between tumors. It refers to cancer cells describing variations in morphology, transcriptional profiles, metabolism, and metastatic potential. More recently, the field has included the characterization of the tumor immune microenvironment and the depiction of the dynamics underlying the cellular interactions promoting the tumor ecosystem evolution. Heterogeneity has been found in most tumors representing one of the most challenging behaviors in cancer ecosystems. As one of the critical factors impairing the long-term efficacy of solid tumor therapy, heterogeneity leads to tumor resistance, more aggressive metastasizing, and recurrence. We review the role of the main models and the emerging single-cell and spatial genomic technologies in our understanding of tumor heterogeneity, its contribution to lethal cancer outcomes, and the physiological challenges to consider in designing cancer therapies. We highlight how tumor cells dynamically evolve because of the interactions within the tumor immune microenvironment and how to leverage this to unleash immune recognition through immunotherapy. A multidisciplinary approach grounded in novel bioinformatic and computational tools will allow reaching the integrated, multilayered knowledge of tumor heterogeneity required to implement personalized, more efficient therapies urgently required for cancer patients.
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Affiliation(s)
- Marco Proietto
- Next Generation Sequencing Core, The Salk Institute for Biological Studies, La Jolla, CA, United States
- Gene Expression Laboratory, The Salk Institute for Biological Studies, La Jolla, CA, United States
- NOMIS Center for Immunobiology and Microbial Pathogenesis, The Salk Institute for Biological Studies, La Jolla, CA, United States
| | - Martina Crippa
- Vita-Salute San Raffaele University, Milan, Italy
- Experimental Imaging Center, Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS) Ospedale San Raffaele, Milan, Italy
| | - Chiara Damiani
- Infrastructure Systems Biology Europe /Centre of Systems Biology (ISBE/SYSBIO) Centre of Systems Biology, Milan, Italy
- Department of Biotechnology and Biosciences, School of Sciences, University of Milano-Bicocca, Milan, Italy
| | - Valentina Pasquale
- Infrastructure Systems Biology Europe /Centre of Systems Biology (ISBE/SYSBIO) Centre of Systems Biology, Milan, Italy
- Department of Biotechnology and Biosciences, School of Sciences, University of Milano-Bicocca, Milan, Italy
| | - Elena Sacco
- Infrastructure Systems Biology Europe /Centre of Systems Biology (ISBE/SYSBIO) Centre of Systems Biology, Milan, Italy
- Department of Biotechnology and Biosciences, School of Sciences, University of Milano-Bicocca, Milan, Italy
| | - Marco Vanoni
- Infrastructure Systems Biology Europe /Centre of Systems Biology (ISBE/SYSBIO) Centre of Systems Biology, Milan, Italy
- Department of Biotechnology and Biosciences, School of Sciences, University of Milano-Bicocca, Milan, Italy
| | - Mara Gilardi
- NOMIS Center for Immunobiology and Microbial Pathogenesis, The Salk Institute for Biological Studies, La Jolla, CA, United States
- Salk Cancer Center, The Salk Institute for Biological Studies, La Jolla, CA, United States
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9
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Bessho T, Takagi T, Igawa K, Sato K. Gelatin-based cell culture device for construction and X-ray irradiation of a three-dimensional oral cancer model. ANAL SCI 2023; 39:771-778. [PMID: 36848001 DOI: 10.1007/s44211-023-00308-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2023] [Accepted: 02/19/2023] [Indexed: 03/01/2023]
Abstract
Bioassays using three-dimensional (3D) tissue models offer several advantages over 2D culture assays because they can reproduce the structure and function of native tissues. In this study, we used our newly designed gelatin device to generate a miniature 3D model of human oral squamous cell carcinoma with stroma and blood vessels. To enable air-liquid interface culture, we conceived a new device structure in which three wells were lined up and separated by a dividing thread; the wells could be connected by removing the dividing thread. Cells were seeded in the center well with the dividing thread to form a multilayer, followed by the supply of media from the side wells after thread removal. Human oral squamous cell carcinoma (HSC-4) cells, human umbilical vein endothelial cells (HUVECs), and normal human dermal fibroblasts (NHDFs) were successfully cocultured, resulting in structures that mimicked 3D-cancer tissues. This 3D-cancer model was subjected to an X-ray sensitivity assay, followed by the evaluation of DNA damage using confocal microscopy and section-scanning electron microscopy.
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Affiliation(s)
- Tomoka Bessho
- Department of Chemical and Biological Sciences, Faculty of Science, Japan Women's University, 2-8-1 Mejirodai, Bunkyo, Tokyo, 112-8681, Japan
| | - Tomoko Takagi
- Department of Chemical and Biological Sciences, Faculty of Science, Japan Women's University, 2-8-1 Mejirodai, Bunkyo, Tokyo, 112-8681, Japan
| | - Kazuyo Igawa
- Neutron Therapy Research Center, Okayama University, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan
| | - Kae Sato
- Department of Chemical and Biological Sciences, Faculty of Science, Japan Women's University, 2-8-1 Mejirodai, Bunkyo, Tokyo, 112-8681, Japan.
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10
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MS A, RK A, V RB, PR AK, Kasoju N. A versatile approach for temporary storage and shipping of in vitro cultured cells, cell sheets and tissue engineered constructs – a preliminary report. ENGINEERED REGENERATION 2022. [DOI: 10.1016/j.engreg.2022.07.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022] Open
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Moya-Garcia CR, Okuyama H, Sadeghi N, Li J, Tabrizian M, Li-Jessen NYK. In vitro models for head and neck cancer: Current status and future perspective. Front Oncol 2022; 12:960340. [PMID: 35992863 PMCID: PMC9381731 DOI: 10.3389/fonc.2022.960340] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2022] [Accepted: 06/29/2022] [Indexed: 12/12/2022] Open
Abstract
The 5-year overall survival rate remains approximately 50% for head and neck (H&N) cancer patients, even though new cancer drugs have been approved for clinical use since 2016. Cancer drug studies are now moving toward the use of three-dimensional culture models for better emulating the unique tumor microenvironment (TME) and better predicting in vivo response to cancer treatments. Distinctive TME features, such as tumor geometry, heterogenous cellularity, and hypoxic cues, notably affect tissue aggressiveness and drug resistance. However, these features have not been fully incorporated into in vitro H&N cancer models. This review paper aims to provide a scholarly assessment of the designs, contributions, and limitations of in vitro models in H&N cancer drug research. We first review the TME features of H&N cancer that are most relevant to in vitro drug evaluation. We then evaluate a selection of advanced culture models, namely, spheroids, organotypic models, and microfluidic chips, in their applications for H&N cancer drug research. Lastly, we propose future opportunities of in vitro H&N cancer research in the prospects of high-throughput drug screening and patient-specific drug evaluation.
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Affiliation(s)
| | - Hideaki Okuyama
- School of Communication Sciences and Disorders, McGill University, Montreal, QC, Canada
- Department of Otolaryngology – Head & Neck Surgery, Kyoto University, Kyoto, Japan
| | - Nader Sadeghi
- Department of Otolaryngology – Head and Neck Surgery, McGill University, Montreal, QC, Canada
- Research Institute of McGill University Health Center, McGill University, Montreal, QC, Canada
| | - Jianyu Li
- Department of Biomedical Engineering, McGill University, Montreal, QC, Canada
- Department of Mechanical Engineering, McGill University, Montreal, QC, Canada
| | - Maryam Tabrizian
- Department of Biomedical Engineering, McGill University, Montreal, QC, Canada
- Faculty of Dental Medicine and Oral Health Sciences, McGill University, Montreal, QC, Canada
- *Correspondence: Maryam Tabrizian, ; Nicole Y. K. Li-Jessen,
| | - Nicole Y. K. Li-Jessen
- Department of Biomedical Engineering, McGill University, Montreal, QC, Canada
- School of Communication Sciences and Disorders, McGill University, Montreal, QC, Canada
- Department of Otolaryngology – Head and Neck Surgery, McGill University, Montreal, QC, Canada
- Research Institute of McGill University Health Center, McGill University, Montreal, QC, Canada
- *Correspondence: Maryam Tabrizian, ; Nicole Y. K. Li-Jessen,
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Dankó T, Petővári G, Raffay R, Sztankovics D, Moldvai D, Vetlényi E, Krencz I, Rókusz A, Sipos K, Visnovitz T, Pápay J, Sebestyén A. Characterisation of 3D Bioprinted Human Breast Cancer Model for In Vitro Drug and Metabolic Targeting. Int J Mol Sci 2022; 23:ijms23137444. [PMID: 35806452 PMCID: PMC9267600 DOI: 10.3390/ijms23137444] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2022] [Revised: 06/26/2022] [Accepted: 06/27/2022] [Indexed: 02/07/2023] Open
Abstract
Monolayer cultures, the less standard three-dimensional (3D) culturing systems, and xenografts are the main tools used in current basic and drug development studies of cancer research. The aim of biofabrication is to design and construct a more representative in vivo 3D environment, replacing two-dimensional (2D) cell cultures. Here, we aim to provide a complex comparative analysis of 2D and 3D spheroid culturing, and 3D bioprinted and xenografted breast cancer models. We established a protocol to produce alginate-based hydrogel bioink for 3D bioprinting and the long-term culturing of tumour cells in vitro. Cell proliferation and tumourigenicity were assessed with various tests. Additionally, the results of rapamycin, doxycycline and doxorubicin monotreatments and combinations were also compared. The sensitivity and protein expression profile of 3D bioprinted tissue-mimetic scaffolds showed the highest similarity to the less drug-sensitive xenograft models. Several metabolic protein expressions were examined, and the in situ tissue heterogeneity representing the characteristics of human breast cancers was also verified in 3D bioprinted and cultured tissue-mimetic structures. Our results provide additional steps in the direction of representing in vivo 3D situations in in vitro studies. Future use of these models could help to reduce the number of animal experiments and increase the success rate of clinical phase trials.
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Affiliation(s)
- Titanilla Dankó
- Department of Pathology and Experimental Cancer Research, Semmelweis University, Üllői út 26, 1085 Budapest, Hungary; (T.D.); (G.P.); (R.R.); (D.S.); (D.M.); (E.V.); (I.K.); (A.R.); (K.S.); (J.P.)
| | - Gábor Petővári
- Department of Pathology and Experimental Cancer Research, Semmelweis University, Üllői út 26, 1085 Budapest, Hungary; (T.D.); (G.P.); (R.R.); (D.S.); (D.M.); (E.V.); (I.K.); (A.R.); (K.S.); (J.P.)
| | - Regina Raffay
- Department of Pathology and Experimental Cancer Research, Semmelweis University, Üllői út 26, 1085 Budapest, Hungary; (T.D.); (G.P.); (R.R.); (D.S.); (D.M.); (E.V.); (I.K.); (A.R.); (K.S.); (J.P.)
| | - Dániel Sztankovics
- Department of Pathology and Experimental Cancer Research, Semmelweis University, Üllői út 26, 1085 Budapest, Hungary; (T.D.); (G.P.); (R.R.); (D.S.); (D.M.); (E.V.); (I.K.); (A.R.); (K.S.); (J.P.)
| | - Dorottya Moldvai
- Department of Pathology and Experimental Cancer Research, Semmelweis University, Üllői út 26, 1085 Budapest, Hungary; (T.D.); (G.P.); (R.R.); (D.S.); (D.M.); (E.V.); (I.K.); (A.R.); (K.S.); (J.P.)
| | - Enikő Vetlényi
- Department of Pathology and Experimental Cancer Research, Semmelweis University, Üllői út 26, 1085 Budapest, Hungary; (T.D.); (G.P.); (R.R.); (D.S.); (D.M.); (E.V.); (I.K.); (A.R.); (K.S.); (J.P.)
| | - Ildikó Krencz
- Department of Pathology and Experimental Cancer Research, Semmelweis University, Üllői út 26, 1085 Budapest, Hungary; (T.D.); (G.P.); (R.R.); (D.S.); (D.M.); (E.V.); (I.K.); (A.R.); (K.S.); (J.P.)
| | - András Rókusz
- Department of Pathology and Experimental Cancer Research, Semmelweis University, Üllői út 26, 1085 Budapest, Hungary; (T.D.); (G.P.); (R.R.); (D.S.); (D.M.); (E.V.); (I.K.); (A.R.); (K.S.); (J.P.)
| | - Krisztina Sipos
- Department of Pathology and Experimental Cancer Research, Semmelweis University, Üllői út 26, 1085 Budapest, Hungary; (T.D.); (G.P.); (R.R.); (D.S.); (D.M.); (E.V.); (I.K.); (A.R.); (K.S.); (J.P.)
| | - Tamás Visnovitz
- Department of Genetics, Cell- and Immunobiology, Semmelweis University, Nagyvárad tér 4, 1089 Budapest, Hungary;
- Department of Plant Physiology and Molecular Plant Biology, ELTE Eötvös Loránd University, Pázmány Péter Sétány 1/c, 1117 Budapest, Hungary
| | - Judit Pápay
- Department of Pathology and Experimental Cancer Research, Semmelweis University, Üllői út 26, 1085 Budapest, Hungary; (T.D.); (G.P.); (R.R.); (D.S.); (D.M.); (E.V.); (I.K.); (A.R.); (K.S.); (J.P.)
| | - Anna Sebestyén
- Department of Pathology and Experimental Cancer Research, Semmelweis University, Üllői út 26, 1085 Budapest, Hungary; (T.D.); (G.P.); (R.R.); (D.S.); (D.M.); (E.V.); (I.K.); (A.R.); (K.S.); (J.P.)
- Correspondence: or
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Three-Dimensional (3D) Printing in Cancer Therapy and Diagnostics: Current Status and Future Perspectives. Pharmaceuticals (Basel) 2022; 15:ph15060678. [PMID: 35745597 PMCID: PMC9229198 DOI: 10.3390/ph15060678] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2022] [Revised: 05/23/2022] [Accepted: 05/25/2022] [Indexed: 12/10/2022] Open
Abstract
Three-dimensional (3D) printing is a technique where the products are printed layer-by-layer via a series of cross-sectional slices with the exact deposition of different cell types and biomaterials based on computer-aided design software. Three-dimensional printing can be divided into several approaches, such as extrusion-based printing, laser-induced forward transfer-based printing systems, and so on. Bio-ink is a crucial tool necessary for the fabrication of the 3D construct of living tissue in order to mimic the native tissue/cells using 3D printing technology. The formation of 3D software helps in the development of novel drug delivery systems with drug screening potential, as well as 3D constructs of tumor models. Additionally, several complex structures of inner tissues like stroma and channels of different sizes are printed through 3D printing techniques. Three-dimensional printing technology could also be used to develop therapy training simulators for educational purposes so that learners can practice complex surgical procedures. The fabrication of implantable medical devices using 3D printing technology with less risk of infections is receiving increased attention recently. A Cancer-on-a-chip is a microfluidic device that recreates tumor physiology and allows for a continuous supply of nutrients or therapeutic compounds. In this review, based on the recent literature, we have discussed various printing methods for 3D printing and types of bio-inks, and provided information on how 3D printing plays a crucial role in cancer management.
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Cinat D, Coppes RP, Barazzuol L. DNA Damage-Induced Inflammatory Microenvironment and Adult Stem Cell Response. Front Cell Dev Biol 2021; 9:729136. [PMID: 34692684 PMCID: PMC8531638 DOI: 10.3389/fcell.2021.729136] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2021] [Accepted: 08/18/2021] [Indexed: 12/14/2022] Open
Abstract
Adult stem cells ensure tissue homeostasis and regeneration after injury. Due to their longevity and functional requirements, throughout their life stem cells are subject to a significant amount of DNA damage. Genotoxic stress has recently been shown to trigger a cascade of cell- and non-cell autonomous inflammatory signaling pathways, leading to the release of pro-inflammatory factors and an increase in the amount of infiltrating immune cells. In this review, we discuss recent evidence of how DNA damage by affecting the microenvironment of stem cells present in adult tissues and neoplasms can affect their maintenance and long-term function. We first focus on the importance of self-DNA sensing in immunity activation, inflammation and secretion of pro-inflammatory factors mediated by activation of the cGAS-STING pathway, the ZBP1 pathogen sensor, the AIM2 and NLRP3 inflammasomes. Alongside cytosolic DNA, the emerging roles of cytosolic double-stranded RNA and mitochondrial DNA are discussed. The DNA damage response can also initiate mechanisms to limit division of damaged stem/progenitor cells by inducing a permanent state of cell cycle arrest, known as senescence. Persistent DNA damage triggers senescent cells to secrete senescence-associated secretory phenotype (SASP) factors, which can act as strong immune modulators. Altogether these DNA damage-mediated immunomodulatory responses have been shown to affect the homeostasis of tissue-specific stem cells leading to degenerative conditions. Conversely, the release of specific cytokines can also positively impact tissue-specific stem cell plasticity and regeneration in addition to enhancing the activity of cancer stem cells thereby driving tumor progression. Further mechanistic understanding of the DNA damage-induced immunomodulatory response on the stem cell microenvironment might shed light on age-related diseases and cancer, and potentially inform novel treatment strategies.
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Affiliation(s)
- Davide Cinat
- Department of Biomedical Sciences of Cells and Systems, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.,Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
| | - Robert P Coppes
- Department of Biomedical Sciences of Cells and Systems, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.,Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
| | - Lara Barazzuol
- Department of Biomedical Sciences of Cells and Systems, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.,Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
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