Human Experimental Models in Molecular Pharmacology

A special issue of Biology (ISSN 2079-7737).

Deadline for manuscript submissions: closed (31 March 2022) | Viewed by 12612

Special Issue Editor


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Guest Editor
Department of Geriatric Medicine, RWTH University Hospital, 52074 Aachen, Germany
Interests: drug discovery; translational genomics; molecular biology; cell biology; molecular pharmacology; gene regulation

Special Issue Information

Dear Colleagues,

Animal models have long had an important role in the development of novel drugs. When a new drug or disease target is discovered, lead candidate molecules are then optimized using preclinical testing in animal models. However, generalizing results from animal models to humans has become a critical biomedical challenge causing failures in moving therapeutics from preclinical studies to clinical trials.

This Special Issue will feature the latest scientific research in the development of human experimental models or the improvement of their utility in one of the most rapidly growing fields of molecular pharmacology, which investigates the molecular mode of drug action using genetic and molecular biology methods. We aim to outline the usefulness, caveats, and potential of human experimental models. Therefore, humanized animal models or human clinical studies will not be considered for publication in this Special Issue. We encourage the submission of manuscripts that report significant advances in human experimental models, with a special focus on the molecular level, in drug research.

Dr. Mahtab Nourbakhsh
Guest Editor

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Keywords

  • experimental model
  • human
  • compounds
  • drugs
  • molecular biology
  • genetics
  • molecular pharmacology
  • cells
  • tissue

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Published Papers (2 papers)

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Research

13 pages, 3212 KiB  
Article
In Vitro Model of Human Skeletal Muscle Tissue for the Study of Resident Macrophages and Stem Cells
by Dandan Hao, Nils Becker, Eva Mückter, Aline Müller, Miguel Pishnamaz, Leo Cornelis Bollheimer, Frank Hildebrand and Mahtab Nourbakhsh
Biology 2022, 11(6), 936; https://doi.org/10.3390/biology11060936 - 19 Jun 2022
Cited by 3 | Viewed by 3783
Abstract
Findings from studies of muscle regeneration can significantly contribute to the treatment of age-related loss of skeletal muscle mass, which may predispose older adults to severe morbidities. We established a human experimental model using excised skeletal muscle tissues from reconstructive surgeries in eight [...] Read more.
Findings from studies of muscle regeneration can significantly contribute to the treatment of age-related loss of skeletal muscle mass, which may predispose older adults to severe morbidities. We established a human experimental model using excised skeletal muscle tissues from reconstructive surgeries in eight older adults. Muscle samples from each participant were preserved immediately or maintained in agarose medium for the following 5, 9, or 11 days. Immunofluorescence analyses of the structural proteins, actin and desmin, confirmed the integrity of muscle fibers over 11 days of maintenance. Similarly, the numbers of CD80-positive M1 and CD163-positive M2 macrophages were stable over 11 days in vitro. However, the numbers of PAX7-positive satellite cells and MYOD-positive myoblasts changed in opposite ways, suggesting that satellite cells partially differentiated in vitro. Further experiments revealed that stimulation with unsaturated fatty acid C18[2]c (linoleic acid) increased resident M1 macrophages and satellite cells specifically. Thus, the use of human skeletal muscle tissue in vitro provides a direct experimental approach to study the regulation of muscle tissue regeneration by macrophages and stem cells and their responses to therapeutic compounds. Full article
(This article belongs to the Special Issue Human Experimental Models in Molecular Pharmacology)
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16 pages, 3987 KiB  
Article
Retinoic Acid-Differentiated Neuroblastoma SH-SY5Y Is an Accessible In Vitro Model to Study Native Human Acid-Sensing Ion Channels 1a (ASIC1a)
by Aleksandr P. Kalinovskii, Dmitry I. Osmakov, Sergey G. Koshelev, Kseniya I. Lubova, Yuliya V. Korolkova, Sergey A. Kozlov and Yaroslav A. Andreev
Biology 2022, 11(2), 167; https://doi.org/10.3390/biology11020167 - 20 Jan 2022
Cited by 12 | Viewed by 7879
Abstract
Human neuroblastoma SH-SY5Y is a prominent neurobiological tool used for studying neuropathophysiological processes. We investigated acid-sensing (ASIC) and transient receptor potential vanilloid-1 (TRPV1) and ankyrin-1 (TRPA1) ion channels present in untreated and differentiated neuroblastoma SH-SY5Y to propose a new means for their study [...] Read more.
Human neuroblastoma SH-SY5Y is a prominent neurobiological tool used for studying neuropathophysiological processes. We investigated acid-sensing (ASIC) and transient receptor potential vanilloid-1 (TRPV1) and ankyrin-1 (TRPA1) ion channels present in untreated and differentiated neuroblastoma SH-SY5Y to propose a new means for their study in neuronal-like cells. Using a quantitative real-time PCR and a whole-cell patch-clamp technique, ion channel expression profiles, functionality, and the pharmacological actions of their ligands were characterized. A low-level expression of ASIC1a and ASIC2 was detected in untreated cells. The treatment with 10 μM of retinoic acid (RA) for 6 days resulted in neuronal differentiation that was accompanied by a remarkable increase in ASIC1a expression, while ASIC2 expression remained almost unaltered. In response to acid stimuli, differentiated cells showed prominent ASIC-like currents. Detailed kinetic and pharmacological characterization suggests that homomeric ASIC1a is a dominant isoform among the present ASIC channels. RA-treatment also reduced the expression of TRPV1 and TRPA1, and minor electrophysiological responses to their agonists were found in untreated cells. Neuroblastoma SH-SY5Y treated with RA can serve as a model system to study the effects of different ligands on native human ASIC1a in neuronal-like cells. This approach can improve the characterization of modulators for the development of new neuroprotective and analgesic drugs. Full article
(This article belongs to the Special Issue Human Experimental Models in Molecular Pharmacology)
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