TY - JOUR
T1 - Role of iron and iron-related proteins in mesenchymal stem cells: Cellular and clinical aspects
AU - Mehta, Kosha
N1 - Funding Information:
This article was made open access with the financial support of King's College London.
Publisher Copyright:
© 2021 The Authors. Journal of Cellular Physiology published by Wiley Periodicals LLC
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/4
Y1 - 2021/4
N2 - Mesenchymal stem cells (MSCs) are located in various tissues where these cells show niche-dependent multilineage differentiation and secrete immunomodulatory molecules to support numerous physiological processes. Due to their regenerative and reparative properties, MSCs are extremely valuable for cell-based therapy in tackling several pathological conditions including COVID-19. Iron is essential for MSC processes but iron-loading, which is common in several chronic conditions, hinders normal MSC functionality. This not only aggravates disease pathology but can also affect allogeneic and autologous MSC therapy. Thus, understanding MSCs from an iron perspective is of clinical significance. Accordingly, this review highlights the roles of iron and iron-related proteins in MSC physiology. It describes the contribution of iron and endogenous iron-related effectors like hepcidin, ferroportin, transferrin receptor, lactoferrin, lipocalin-2, bone morphogenetic proteins and hypoxia inducible factors in MSC biology. It summarises the excess-iron-induced alterations in MSC components, processes and discusses signalling pathways involving ROS, PI3K/AKT, MAPK, p53, AMPK/MFF/DRP1 and Wnt. Additionally, it evaluates the endogenous and exogenous saviours of MSCs against iron-toxicity. Lastly, it elaborates on the involvement of MSCs in the pathology of clinical conditions of iron-excess, namely, hereditary hemochromatosis, diabetes, β-thalassaemia and myelodysplastic syndromes. This unique review integrates the distinct fields of iron regulation and MSC physiology. Through an iron-perspective, it describes both mechanistic and clinical aspects of MSCs and proposes an iron-linked MSC-contribution to physiology, pathology and therapeutics. It advances the understanding of MSC biology and may aid in identifying signalling pathways, molecular targets and compounds for formulating adjunctive iron-based therapies for excess-iron conditions, and thereby inform regenerative medicine.
AB - Mesenchymal stem cells (MSCs) are located in various tissues where these cells show niche-dependent multilineage differentiation and secrete immunomodulatory molecules to support numerous physiological processes. Due to their regenerative and reparative properties, MSCs are extremely valuable for cell-based therapy in tackling several pathological conditions including COVID-19. Iron is essential for MSC processes but iron-loading, which is common in several chronic conditions, hinders normal MSC functionality. This not only aggravates disease pathology but can also affect allogeneic and autologous MSC therapy. Thus, understanding MSCs from an iron perspective is of clinical significance. Accordingly, this review highlights the roles of iron and iron-related proteins in MSC physiology. It describes the contribution of iron and endogenous iron-related effectors like hepcidin, ferroportin, transferrin receptor, lactoferrin, lipocalin-2, bone morphogenetic proteins and hypoxia inducible factors in MSC biology. It summarises the excess-iron-induced alterations in MSC components, processes and discusses signalling pathways involving ROS, PI3K/AKT, MAPK, p53, AMPK/MFF/DRP1 and Wnt. Additionally, it evaluates the endogenous and exogenous saviours of MSCs against iron-toxicity. Lastly, it elaborates on the involvement of MSCs in the pathology of clinical conditions of iron-excess, namely, hereditary hemochromatosis, diabetes, β-thalassaemia and myelodysplastic syndromes. This unique review integrates the distinct fields of iron regulation and MSC physiology. Through an iron-perspective, it describes both mechanistic and clinical aspects of MSCs and proposes an iron-linked MSC-contribution to physiology, pathology and therapeutics. It advances the understanding of MSC biology and may aid in identifying signalling pathways, molecular targets and compounds for formulating adjunctive iron-based therapies for excess-iron conditions, and thereby inform regenerative medicine.
UR - http://www.scopus.com/inward/record.url?scp=85103561366&partnerID=8YFLogxK
U2 - 10.1002/jcp.30383
DO - 10.1002/jcp.30383
M3 - Review article
SN - 0021-9541
VL - 236
SP - 7266
EP - 7289
JO - Journal of Cellular Physiology
JF - Journal of Cellular Physiology
IS - 10
ER -