A Review of the Evidence for Tryptophan and the Kynurenine Pathway as a Regulator of Stem Cell Niches in Health and Disease.

Autor: Summers BS; Applied Neurosciences Program, Peter Duncan Neurosciences Research Unit, St. Vincent's Centre for Applied Medical Research, Sydney, NSW, Australia.; Faculty of Medicine and Health, School of Clinical Medicine, UNSW Sydney, NSW, Australia., Thomas Broome S; Faculty of Science, Laboratory of Cellular and Molecular Neuroscience, School of Life Sciences, University of Technology Sydney, NSW, Australia., Pang TWR; Faculty of Medicine and Health, The University of Sydney, NSW, Australia., Mundell HD; Faculty of Medicine and Health, New South Wales Brain Tissue Resource Centre, School of Medical Sciences, Charles Perkins Centre, University of Sydney, NSW, Australia., Koh Belic N; School of Life Sciences, University of Technology, Sydney, NSW, Australia., Tom NC; Formerly of the Department of Physiology, University of Sydney, NSW, Australia., Ng ML; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore., Yap M; Formerly of the Atherothrombosis and Vascular Biology Laboratory, Baker Heart and Diabetes Institute, Melbourne, VIC, Australia., Sen MK; Applied Neurosciences Program, Peter Duncan Neurosciences Research Unit, St. Vincent's Centre for Applied Medical Research, Sydney, NSW, Australia.; School of Medicine, Western Sydney University, NSW, Australia.; Faculty of Medicine and Health, School of Medical Sciences, Charles Perkins Centre, The University of Sydney, NSW, Australia., Sedaghat S; Montreal Neurological Institute, McGill University, Montreal, QC, Canada., Weible MW; School of Environment and Science, Griffith University, Brisbane, QLD, Australia.; Griffith Institute for Drug Discovery, Griffith University, Brisbane, QLD, Australia., Castorina A; Faculty of Science, Laboratory of Cellular and Molecular Neuroscience, School of Life Sciences, University of Technology Sydney, NSW, Australia., Lim CK; Faculty of Medicine, Macquarie University, Sydney, NSW, Australia., Lovelace MD; Applied Neurosciences Program, Peter Duncan Neurosciences Research Unit, St. Vincent's Centre for Applied Medical Research, Sydney, NSW, Australia.; Faculty of Medicine and Health, School of Clinical Medicine, UNSW Sydney, NSW, Australia., Brew BJ; Applied Neurosciences Program, Peter Duncan Neurosciences Research Unit, St. Vincent's Centre for Applied Medical Research, Sydney, NSW, Australia.; Faculty of Medicine and Health, School of Clinical Medicine, UNSW Sydney, NSW, Australia.; Departments of Neurology and Immunology, St. Vincent's Hospital, Sydney, NSW, Australia.; University of Notre Dame, Darlinghurst, Sydney, NSW, Australia.
Jazyk: angličtina
Zdroj: International journal of tryptophan research : IJTR [Int J Tryptophan Res] 2024 May 15; Vol. 17, pp. 11786469241248287. Date of Electronic Publication: 2024 May 15 (Print Publication: 2024).
DOI: 10.1177/11786469241248287
Abstrakt: Stem cells are ubiquitously found in various tissues and organs in the body, and underpin the body's ability to repair itself following injury or disease initiation, though repair can sometimes be compromised. Understanding how stem cells are produced, and functional signaling systems between different niches is critical to understanding the potential use of stem cells in regenerative medicine. In this context, this review considers kynurenine pathway (KP) metabolism in multipotent adult progenitor cells, embryonic, haematopoietic, neural, cancer, cardiac and induced pluripotent stem cells, endothelial progenitor cells, and mesenchymal stromal cells. The KP is the major enzymatic pathway for sequentially catabolising the essential amino acid tryptophan (TRP), resulting in key metabolites including kynurenine, kynurenic acid, and quinolinic acid (QUIN). QUIN metabolism transitions into the adjoining de novo pathway for nicotinamide adenine dinucleotide (NAD) production, a critical cofactor in many fundamental cellular biochemical pathways. How stem cells uptake and utilise TRP varies between different species and stem cell types, because of their expression of transporters and responses to inflammatory cytokines. Several KP metabolites are physiologically active, with either beneficial or detrimental outcomes, and evidence of this is presented relating to several stem cell types, which is important as they may exert a significant impact on surrounding differentiated cells, particularly if they metabolise or secrete metabolites differently. Interferon-gamma (IFN-γ) in mesenchymal stromal cells, for instance, highly upregulates rate-limiting enzyme indoleamine-2,3-dioxygenase (IDO-1), initiating TRP depletion and production of metabolites including kynurenine/kynurenic acid, known agonists of the Aryl hydrocarbon receptor (AhR) transcription factor. AhR transcriptionally regulates an immunosuppressive phenotype, making them attractive for regenerative therapy. We also draw attention to important gaps in knowledge for future studies, which will underpin future application for stem cell-based cellular therapies or optimising drugs which can modulate the KP in innate stem cell populations, for disease treatment.
Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Prof. Bruce Brew is a member of the International Journal for Tryptophan Research journal editorial board. The other co-authors declare that they have no conflict of interest.
(© The Author(s) 2024.)
Databáze: MEDLINE
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