scholarly journals Photodynamic Therapy-Mediated Immune Responses in Three-Dimensional Tumor Models

2021 ◽  
Vol 22 (23) ◽  
pp. 12618
Author(s):  
Nkune Williams Nkune ◽  
Nokuphila Winifred Nompumelelo Simelane ◽  
Hanieh Montaseri ◽  
Heidi Abrahamse
Keyword(s):  
Photodynamic Therapy ◽  
Immune Responses ◽  
Three Dimensional ◽  
Tumor Model ◽  
Experimental Models ◽  
Cellular Heterogeneity ◽  
Tumor Models ◽  
Cellular Environment

Photodynamic therapy (PDT) is a promising non-invasive phototherapeutic approach for cancer therapy that can eliminate local tumor cells and produce systemic antitumor immune responses. In recent years, significant efforts have been made in developing strategies to further investigate the immune mechanisms triggered by PDT. The majority of in vitro experimental models still rely on the two-dimensional (2D) cell cultures that do not mimic a three-dimensional (3D) cellular environment in the human body, such as cellular heterogeneity, nutrient gradient, growth mechanisms, and the interaction between cells as well as the extracellular matrix (ECM) and therapeutic resistance to anticancer treatments. In addition, in vivo animal studies are highly expensive and time consuming, which may also show physiological discrepancies between animals and humans. In this sense, there is growing interest in the utilization of 3D tumor models, since they precisely mimic different features of solid tumors. This review summarizes the characteristics and techniques for 3D tumor model generation. Furthermore, we provide an overview of innate and adaptive immune responses induced by PDT in several in vitro and in vivo tumor models. Future perspectives are highlighted for further enhancing PDT immune responses as well as ideal experimental models for antitumor immune response studies.

Epithelial Organotypic Cultures: A Viable Model to Address Mechanisms of Carcinogenesis by Epitheliotropic Viruses

2018 ◽  
Vol 18 (4) ◽  
pp. 246-255 ◽  
Author(s):  
Lara Termini ◽  
Enrique Boccardo
Keyword(s):  
Three Dimensional ◽  
Cell Types ◽  
Experimental Models ◽  
Biological Research ◽  
Specific Gene ◽  
Specific Cell ◽  
Organotypic Cultures ◽  
Skin Physiology

In vitro culture of primary or established cell lines is one of the leading techniques in many areas of basic biological research. The use of pure or highly enriched cultures of specific cell types obtained from different tissues and genetics backgrounds has greatly contributed to our current understanding of normal and pathological cellular processes. Cells in culture are easily propagated generating an almost endless source of material for experimentation. Besides, they can be manipulated to achieve gene silencing, gene overexpression and genome editing turning possible the dissection of specific gene functions and signaling pathways. However, monolayer and suspension cultures of cells do not reproduce the cell type diversity, cell-cell contacts, cell-matrix interactions and differentiation pathways typical of the three-dimensional environment of tissues and organs from where they were originated. Therefore, different experimental animal models have been developed and applied to address these and other complex issues in vivo. However, these systems are costly and time consuming. Most importantly the use of animals in scientific research poses moral and ethical concerns facing a steadily increasing opposition from different sectors of the society. Therefore, there is an urgent need for the development of alternative in vitro experimental models that accurately reproduce the events observed in vivo to reduce the use of animals. Organotypic cultures combine the flexibility of traditional culture systems with the possibility of culturing different cell types in a 3D environment that reproduces both the structure and the physiology of the parental organ. Here we present a summarized description of the use of epithelial organotypic for the study of skin physiology, human papillomavirus biology and associated tumorigenesis.

scholarly journals Organoids of the female reproductive tract

2021 ◽  
Vol 99 (4) ◽  
pp. 531-553 ◽  
Author(s):  
Cindrilla Chumduri ◽  
Margherita Y. Turco
Keyword(s):  
Reproductive Tract ◽  
Personalised Medicine ◽  
Three Dimensional ◽  
In Vitro Models ◽  
Experimental Models ◽  
Female Reproductive Tract ◽  
Cellular Heterogeneity ◽  
Dynamic Regulation ◽  
Pregnancy And Childbirth

AbstractHealthy functioning of the female reproductive tract (FRT) depends on balanced and dynamic regulation by hormones during the menstrual cycle, pregnancy and childbirth. The mucosal epithelial lining of different regions of the FRT—ovaries, fallopian tubes, uterus, cervix and vagina—facilitates the selective transport of gametes and successful transfer of the zygote to the uterus where it implants and pregnancy takes place. It also prevents pathogen entry. Recent developments in three-dimensional (3D) organoid systems from the FRT now provide crucial experimental models that recapitulate the cellular heterogeneity and physiological, anatomical and functional properties of the organ in vitro. In this review, we summarise the state of the art on organoids generated from different regions of the FRT. We discuss the potential applications of these powerful in vitro models to study normal physiology, fertility, infections, diseases, drug discovery and personalised medicine.

scholarly journals The Challenging Melanoma Landscape: From Early Drug Discovery to Clinical Approval

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3088
Author(s):  
Mariana Matias ◽  
Jacinta O. Pinho ◽  
Maria João Penetra ◽  
Gonçalo Campos ◽  
Catarina Pinto Reis ◽  
...  
Keyword(s):  
Therapeutic Potential ◽  
Drug Evaluation ◽  
Three Dimensional ◽  
Experimental Models ◽  
In Vivo Studies ◽  
Murine Models ◽  
In Vivo Experiments ◽  
Novel Therapeutic Strategies

Melanoma is recognized as the most dangerous type of skin cancer, with high mortality and resistance to currently used treatments. To overcome the limitations of the available therapeutic options, the discovery and development of new, more effective, and safer therapies is required. In this review, the different research steps involved in the process of antimelanoma drug evaluation and selection are explored, including information regarding in silico, in vitro, and in vivo experiments, as well as clinical trial phases. Details are given about the most used cell lines and assays to perform both two- and three-dimensional in vitro screening of drug candidates towards melanoma. For in vivo studies, murine models are, undoubtedly, the most widely used for assessing the therapeutic potential of new compounds and to study the underlying mechanisms of action. Here, the main melanoma murine models are described as well as other animal species. A section is dedicated to ongoing clinical studies, demonstrating the wide interest and successful efforts devoted to melanoma therapy, in particular at advanced stages of the disease, and a final section includes some considerations regarding approval for marketing by regulatory agencies. Overall, considerable commitment is being directed to the continuous development of optimized experimental models, important for the understanding of melanoma biology and for the evaluation and validation of novel therapeutic strategies.

scholarly journals Construction of Lung Tumor Model for Drug Screening Based on 3D Bio-Printing Technology

2021 ◽  
Vol 11 (7) ◽  
pp. 1213-1226
Author(s):  
Yadong Yang ◽  
Geng Yang ◽  
Xingzhu Liu ◽  
Yimeng Xu ◽  
Siyu Zhao ◽  
...  
Keyword(s):  
Lung Cancer ◽  
3D Model ◽  
Cultured Cells ◽  
Lung Tumor ◽  
Three Dimensional ◽  
Tumor Model ◽  
Traditional Chinese Medicines ◽  
Chinese Medicines

As is known to all, the biological characteristics of two-dimensional (2D) cultured cells are quite different from those in vivo, so the 2D screening model can no longer meet people’s needs. With the development of tissue engineering, people are committed to developing 3D tissue models that can better reflect the biology in vivo, and tend to be mass and miniaturized. In this study, three-dimensional (3D) bio-printing was used to develop an appropriate 3D model for screening sensitive anti-lung cancer drugs in vitro. A549 lung cancer cells were mixed with 8% sodium alginate and 5% gelatin as bio-printing ink to fabricate a cell-laden hydrogel grid scaffold structure. The sensitivity of the printed 3D model to drugs was evaluated with eight anti-tumor traditional Chinese medicines. A fluorescent live/dead staining was carried out at different time to assess the cell survival rate in the 3D scaffolds. MTT assay was used to determine the inhibitory rate of eight antitumor traditional Chinese medicines on A549 cell proliferation in 3D-printed lung tumor models and conventional 2D culture models.

scholarly journals Modeling the Efficacy of Oncolytic Adenoviruses In Vitro and In Vivo: Current and Future Perspectives

Cancers ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 619 ◽  
Author(s):  
Mary K. McKenna ◽  
Amanda Rosewell-Shaw ◽  
Masataka Suzuki
Keyword(s):  
Immune Responses ◽  
Clinical Success ◽  
Three Dimensional ◽  
Model Systems ◽  
Gene Therapies ◽  
Oncolytic Adenoviruses ◽  
Limited Success ◽  
Clinical Models

Oncolytic adenoviruses (OAd) selectively target and lyse tumor cells and enhance anti- tumor immune responses. OAds have been used as promising cancer gene therapies for many years and there are a multitude of encouraging pre-clinical studies. However, translating OAd therapies to the clinic has had limited success, in part due to the lack of realistic pre-clinical models to rigorously test the efficacy of OAds. Solid tumors have a heterogenous and hostile microenvironment that provides many barriers to OAd treatment, including structural and immunosuppressive components that cannot be modeled in two-dimensional tissue culture. To replicate these characteristics and bridge the gap between pre-clinical and clinical success, studies must test OAd therapy in three-dimensional culture and animal models. This review focuses on current methods to test OAd efficacy in vitro and in vivo and the development of new model systems to test both oncolysis and immune stimulatory components of oncolytic adenovirotherapy.

Self-assembly nanoparticles based on supramolecular-organic frameworks and temoporfin for an enhanced photodynamic therapy in vitro and in vivo

2022 ◽  
Author(s):  
Ziyue Xu ◽  
Weipeng Mao ◽  
Zizhen Zhao ◽  
Zekun Wang ◽  
Yue-Yang Liu ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Self Assembly ◽  
Three Dimensional ◽  
Water Soluble ◽  
Generation Efficiency ◽  
Quenching Effect

Water-soluble three-dimensional supramolecular-organic frameworks (SOFs) and temoporfin (mTHPC) are discovered to form uniform self-assembly nanoparticles. These nanoparticles demonstrate an improved 1O2 generation efficiency due to a reduced aggregation-caused quenching effect....

scholarly journals In vitro cell and tissue models for studying host–microbe interactions: a review

2013 ◽  
Vol 109 (S2) ◽  
pp. S27-S34 ◽  
Author(s):  
Miriam Bermudez-Brito ◽  
Julio Plaza-Díaz ◽  
Luis Fontana ◽  
Sergio Muñoz-Quezada ◽  
Angel Gil
Keyword(s):  
Epithelial Cells ◽  
Molecular Mechanisms ◽  
Three Dimensional ◽  
Experimental Models ◽  
Dynamic Interactions ◽  
Basolateral Side ◽  
Microbe Interactions ◽  
Host Microbe Interactions

Ideally, cell models should resemble the in vivo conditions; however, in most in vitro experimental models, epithelial cells are cultivated as monolayers, in which the establishment of functional epithelial features is not achieved. To overcome this problem, co-culture experiments with probiotics, dendritic cells and intestinal epithelial cells and three-dimensional models attempt to reconcile the complex and dynamic interactions that exist in vivo between the intestinal epithelium and bacteria on the luminal side and between the epithelium and the underlying immune system on the basolateral side. Additional models include tissue explants, bioreactors and organoids. The present review details the in vitro models used to study host–microbe interactions and explores the new tools that may help in understanding the molecular mechanisms of these interactions.

scholarly journals Spheres of Influence: Insights into Salmonella Pathogenesis from Intestinal Organoids

2020 ◽  
Vol 8 (4) ◽  
pp. 504 ◽  
Author(s):  
Smriti Verma ◽  
Stefania Senger ◽  
Bobby J. Cherayil ◽  
Christina S. Faherty
Keyword(s):  
Animal Studies ◽  
Three Dimensional ◽  
Cell Types ◽  
Experimental Models ◽  
Primary Cells ◽  
Spheres Of Influence ◽  
Transformed Cell Lines ◽  
And Function

The molecular complexity of host-pathogen interactions remains poorly understood in many infectious diseases, particularly in humans due to the limited availability of reliable and specific experimental models. To bridge the gap between classical two-dimensional culture systems, which often involve transformed cell lines that may not have all the physiologic properties of primary cells, and in vivo animal studies, researchers have developed the organoid model system. Organoids are complex three-dimensional structures that are generated in vitro from primary cells and can recapitulate key in vivo properties of an organ such as structural organization, multicellularity, and function. In this review, we discuss how organoids have been deployed in exploring Salmonella infection in mice and humans. In addition, we summarize the recent advancements that hold promise to elevate our understanding of the interactions and crosstalk between multiple cell types and the microbiota with Salmonella. These models have the potential for improving clinical outcomes and future prophylactic and therapeutic intervention strategies.

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