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Recent advances in understanding mesenchymal stromal cells.

ABSTRACT: Mesenchymal stromal cells (MSCs) are among of the most studied cell type for cellular therapy thanks to the ease of isolation, cultivation, and the high ex vivo expansion potential. In 2018, the European Medicines Agency finally granted the first marketing authorization for an MSC product. Despite the numerous promising results in preclinical studies, translation into routine practice still lags behind: therapeutic benefits of MSCs are not as satisfactory in clinical trial settings as they appear to be in preclinical models. The bench-to-bedside-and-back approach and careful evaluation of discrepancies between preclinical and clinical results have provided valuable insights into critical components of MSC manufacturing, their mechanisms of action, and how to evaluate and quality-control them. We sum up these past developments in the introductory section ("Mesenchymal stromal cells: name follows function"). From the huge amount of information, we then selected a few examples to illustrate challenges and opportunities to improve MSCs for clinical purposes. These include tissue origin of MSCs, MSC culture conditions, immune compatibility, and route of application and dosing. Finally, we add some information on MSC mechanisms of action and translation into potency assays and give an outlook on future perspectives raising the question of whether the future clinical product may be cell-based or cell-derived.

SUBMITTER: Rendra E

PROVIDER: S-EPMC7047922 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Recent advances in understanding mesenchymal stromal cells.

Rendra Erika E Scaccia Eleonora E Bieback Karen K

F1000Research 20200227

Mesenchymal stromal cells (MSCs) are among of the most studied cell type for cellular therapy thanks to the ease of isolation, cultivation, and the high <i>ex vivo</i> expansion potential. In 2018, the European Medicines Agency finally granted the first marketing authorization for an MSC product. Despite the numerous promising results in preclinical studies, translation into routine practice still lags behind: therapeutic benefits of MSCs are not as satisfactory in clinical trial settings as the ...[more]

PMID: 32148780

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Project description:Vitiligo, an acquired depigmentation disorder, manifests as white macules on the skin and can cause significant psychological stress and stigmatization. Recent advances have shed light on key components that drive disease onset and progression as well as therapeutic approaches. Vitiligo can be triggered by stress to the melanin pigment-producing cells of the skin, the melanocytes. The triggers, which range from sunburn to mechanical trauma and chemical exposures, ultimately cause an autoimmune response that targets melanocytes, driving progressive skin depigmentation. The most significant progress in our understanding of disease etiology has been made on three fronts: (1) identifying cellular responses to stress, including antioxidant pathways and the unfolded protein response (UPR), as key players in disease onset, (2) characterizing immune responses that target melanocytes and drive disease progression, and (3) identifying major susceptibility genes. The current model for vitiligo pathogenesis postulates that oxidative stress causes cellular disruptions, including interruption of protein maturation in the endoplasmic reticulum (ER), leading to the activation of the UPR and expression of UPR-regulated chemokines such as interleukin 6 (IL-6) and IL-8. These chemokines recruit immune components to the skin, causing melanocytes to be targeted for destruction. Oxidative stress can further increase melanocyte targeting by promoting antigen presentation. Two key components of the autoimmune response that promote disease progression are the interferon (IFN)-?/CXCL10 axis and IL-17-mediated responses. Several genome-wide association studies support a role for these pathways, with the antioxidant gene NRF2, UPR gene XBP1, and numerous immune-related genes including class I and class II major histocompatibility genes associated with a risk for developing vitiligo. Novel approaches to promote repigmentation in vitiligo are being investigated and may yield effective, long-lasting therapies.

Dataset Information

Recent advances in understanding mesenchymal stromal cells.

Publications

Recent advances in understanding mesenchymal stromal cells.

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