Tryptophan in Molecular Hematopoiesis

Haznedaroğlu, İbrahim C.

doi:10.1007/978-3-319-15630-9_11

Cited by 1 publication

(1 citation statement)

References 65 publications

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“…As precursors of cells comprising the immune system, understanding the biology of HSCs is of significant clinical interest in autoimmune diseases, transplantation biology, and myelodysplastic syndromes. 154 Due to their relatively non-invasive accessibility and knowledge built up over the past few decades which led to their use in stem cell transplants, they have been one of the most intensively studied stem cell types.…”

Section: Stem Cellsmentioning

confidence: 99%

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

Summers,

Thomas Broome,

Pang

et al. 2024

Int J�Tryptophan�Res

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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.

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Section: Stem Cellsmentioning

confidence: 99%