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Biology
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Preclinical Models in Translational Medicine
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Preclinical Models in Translational Medicine

A special issue of Biology (ISSN 2079-7737). This special issue belongs to the section "Medical Biology".

Deadline for manuscript submissions: closed (31 December 2021) | Viewed by 22080

Special Issue Editors

Dr. Dario Brunetti

E-Mail Website
Guest Editor
Mitochondrial Medicine Laboratory, Department of Medical Biotechnology and Translational Medicine, University of Milan, Via Vanvitelli 32, 20123 Milan, Italy
Interests: investigating mitochondrial dysfunction in genetic metabolic and aging related disease; production of cell (iPS and organoids) and animal models of neuromuscular disease; development of pharmacological treatment and gene therapy for mitochondrial disease
Special Issues, Collections and Topics in MDPI journals
Dr. Emanuela Bottani

E-Mail Website
Guest Editor
Department of Diagnostic and Public Health, Section of Pharmacology, University of Verona, 37134 Verona, Italy
Interests: mitochondrial medicine; mitochondrial disorders; neuroscience; cellular metabolism
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Translational medicine, also known as disease-targeted research, aims to improve human health by determining the relevance of novel biological sciences discoveries to human disease. Translational medicine is based on a bidirectional concept, which entails the conversion of clinical observations into new research hypotheses and the so-called “from-bench-to-bedside” process, according to which new research discoveries are directly applied to develop new therapeutic protocols for patients.

The recent progresses in molecular genetics, gene editing and stem cell technologies have led to an acceleration in the production and characterization of in vitro and in vivo preclinical models that play a central role in the translational process.

For this Special Issue, authors are invited to present novel data regarding translational medicine, including, but not limited to, the following topics: understanding the patho-mechanisms of human disease; studying cellular and tissue metabolism; developing therapeutic protocols, ranging from regenerative medicine (i.e., stem cell transplantation and xenotransplantation) to pharmacological and gene therapy or combined treatments; performing small or large drug screenings and drug repositioning; discovering novel biomarkers.

This Special Issue welcomes original research articles, comprehensive reviews, and short communications that will supply important novel data.

Dr. Dario Brunetti
Dr. Emanuela Bottani
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biology is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • stem cells
  • organoids
  • animal models
  • drug screening
  • cell therapy
  • gene therapy

Published Papers (4 papers)

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Research

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17 pages, 1718 KiB  
Article
Assessing Scientific Soundness and Translational Value of Animal Studies on DPP4 Inhibitors for Treating Type 2 Diabetes Mellitus
by Nuno Henrique Franco, Sonia Batista Miranda, Nóra Kovács, Attila Nagy, Bùi Quốc Thiện, Flávio Reis and Orsolya Varga
Biology 2021, 10(2), 155; https://doi.org/10.3390/biology10020155 - 16 Feb 2021
Viewed by 3670
Abstract
Although there is a wide range of animal models of type 2 diabetes mellitus (T2DM) used in research; we have limited evidence on their translation value. This paper provides a) a comparison of preclinical animal and clinical results on the effect of five [...] Read more.
Although there is a wide range of animal models of type 2 diabetes mellitus (T2DM) used in research; we have limited evidence on their translation value. This paper provides a) a comparison of preclinical animal and clinical results on the effect of five dipeptidyl peptidase-4 (DPP4) inhibitors by comparing the pharmaceutical caused glucose changes, and b) an evaluation of methodological and reporting standards in T2DM preclinical animal studies. DPP4 inhibitors play an important role in the clinical management of T2DM: if metformin alone is not sufficient enough to control the blood sugar levels, DPP4 inhibitors are often used as second-line therapy; additionally, DPP-4 inhibitors are also used in triple therapies with metformin and sodium-glucose co-transporter-2 (SGLT-2) inhibitors or with metformin and insulin. In our analysis of 124 preclinical studies and 47 clinical trials, (1) we found no evidence of species differences in glucose change response to DPP4 inhibitors, which may suggest that, for this drug class, studies in mice and rats may be equally predictive of how well a drug will work in humans; and (2) there is good reporting of group size, sex, age, euthanasia method and self-reported compliance with animal welfare regulations in animal studies but poor reporting of justification of group size, along with a strong bias towards the use of male animals and young animals. Instead of the common non-transparent model selection, we call for a reflective and evidenced-based assessment of predictive validity of the animal models currently available. Full article
(This article belongs to the Special Issue Preclinical Models in Translational Medicine)
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16 pages, 3336 KiB  
Article
Time-Dependent Pathological Changes in Hypoperfusion-Induced Abdominal Aortic Aneurysm
by Hirona Kugo, Wanida Sukketsiri, Hiroki Tanaka, Rena Fujishima, Tatsuya Moriyama and Nobuhiro Zaima
Biology 2021, 10(2), 149; https://doi.org/10.3390/biology10020149 - 14 Feb 2021
Cited by 8 | Viewed by 2207
Abstract
Hypoperfusion due to vasa vasorum stenosis can cause wall hypoxia and abdominal aortic aneurysm (AAA) development. Even though hypoperfusion is an important contributor toward pathological changes in AAA, the correlation between hypoperfusion and AAA is not fully understood. In this study, a time-dependent [...] Read more.
Hypoperfusion due to vasa vasorum stenosis can cause wall hypoxia and abdominal aortic aneurysm (AAA) development. Even though hypoperfusion is an important contributor toward pathological changes in AAA, the correlation between hypoperfusion and AAA is not fully understood. In this study, a time-dependent semi-quantitative pathological analysis of hypoperfusion-induced aortic wall changes was performed to understand the mechanisms underlying the gradual degradation of the aortic wall leading to AAA formation. AAA-related factors evaluated in this study were grouped according to the timing of dynamic change, and five groups were formed as follows: first group: angiotensin II type 1 receptor, endothelin-1 (ET-1), and malondialdehyde (MDA); second group: matrix metalloproteinase (MMP)-2, -9, -12, M1 macrophages (Mac387+ cells), and monocyte chemotactic protein-1; third group: synthetic smooth muscle cells (SMCs); fourth group: neutrophil elastase, contractile SMCs, and angiotensinogen; and the fifth group: M2 macrophages (CD163+ cells). Hypoxia-inducible factor-1α, ET-1, MDA, and MMP-9 were colocalized with alpha-smooth muscle actin cells in 3 h, suggesting that hypoperfusion-induced hypoxia directly affects the activities of contractile SMCs in the initial stage of AAA. Time-dependent pathological analysis clarified the cascade of AAA-related factors. These findings provide clues for understanding complicated multistage pathologies in AAA. Full article
(This article belongs to the Special Issue Preclinical Models in Translational Medicine)
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Review

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15 pages, 1522 KiB  
Review
Companion Animal Model in Translational Oncology; Feline Oral Squamous Cell Carcinoma and Canine Oral Melanoma
by Antonio Giuliano
Biology 2022, 11(1), 54; https://doi.org/10.3390/biology11010054 - 31 Dec 2021
Cited by 12 | Viewed by 8895
Abstract
Companion animals with naturally occurring cancers can provide an advantageous model for cancer research and in particular anticancer drug development. Compared to commonly utilized mouse models, companion animals, specifically dogs and cats, share a closer phylogenetical distance, body size, and genome organization. Most [...] Read more.
Companion animals with naturally occurring cancers can provide an advantageous model for cancer research and in particular anticancer drug development. Compared to commonly utilized mouse models, companion animals, specifically dogs and cats, share a closer phylogenetical distance, body size, and genome organization. Most importantly, pets develop spontaneous, rather than artificially induced, cancers. The incidence of cancer in people and companion animals is quite similar and cancer is the leading cause of death in dogs over 10 years of age. Many cancer types in dogs and cats have similar pathological, molecular, and clinical features to their human counterparts. Drug toxicity and response to anti-cancer treatment in dogs and cats are also similar to those in people. Companion animals share their lives with their owners, including the environmental and socioeconomic cancer-risk factors. In contrast to humans, pets have a shorter life span and cancer progression is often more rapid. Clinical trials in companion animals are cheaper and less time consuming compared to human trials. Dogs and cats with naturally occurring cancers are an ideal and unique model for human cancer research. Model selection for the specific type of cancer is of pivotal importance. Although companion animal models for translational research have been reviewed previously, this review will try to summarize the most important advantages and disadvantages of this model. Feline oral squamous cell carcinoma as a model for head and neck squamous cell carcinoma and canine oral melanoma as a model for mucosal melanoma and immunotherapy in people will be discussed as examples. Full article
(This article belongs to the Special Issue Preclinical Models in Translational Medicine)
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20 pages, 2887 KiB  
Review
Heterotypic Multicellular Spheroids as Experimental and Preclinical Models of Sprouting Angiogenesis
by Igor V. Vakhrushev, Elizaveta K. Nezhurina, Pavel A. Karalkin, Anastasia V. Tsvetkova, Nataliya S. Sergeeva, Alexander G. Majouga and Konstantin N. Yarygin
Biology 2022, 11(1), 18; https://doi.org/10.3390/biology11010018 - 23 Dec 2021
Cited by 3 | Viewed by 5925
Abstract
Sprouting angiogenesis is the common response of live tissues to physiological and pathological angiogenic stimuli. Its accurate evaluation is of utmost importance for basic research and practical medicine and pharmacology and requires adequate experimental models. A variety of assays for angiogenesis were developed, [...] Read more.
Sprouting angiogenesis is the common response of live tissues to physiological and pathological angiogenic stimuli. Its accurate evaluation is of utmost importance for basic research and practical medicine and pharmacology and requires adequate experimental models. A variety of assays for angiogenesis were developed, none of them perfect. In vitro approaches are generally less physiologically relevant due to the omission of essential components regulating the process. However, only in vitro models can be entirely non-xenogeneic. The limitations of the in vitro angiogenesis assays can be partially overcome using 3D models mimicking tissue O2 and nutrient gradients, the influence of the extracellular matrix (ECM), and enabling cell-cell interactions. Here we present a review of the existing models of sprouting angiogenesis that are based on the use of endothelial cells (ECs) co-cultured with perivascular or other stromal cells. This approach provides an excellent in vitro platform for further decoding of the cellular and molecular mechanisms of sprouting angiogenesis under conditions close to the in vivo conditions, as well as for preclinical drug testing and preclinical research in tissue engineering and regenerative medicine. Full article
(This article belongs to the Special Issue Preclinical Models in Translational Medicine)
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