Mesenchymal stem cells and ferroptosis: Clinical opportunities and challenges

Mengling Cui; Fukun Chen; Lishi Shao; Chanyan Wei; Weihu Zhang; Wenmei Sun; Jiaping Wang

doi:10.1016/j.heliyon.2024.e25251

Mesenchymal stem cells and ferroptosis: Clinical opportunities and challenges

Heliyon. 2024 Feb 3;10(3):e25251. doi: 10.1016/j.heliyon.2024.e25251. eCollection 2024 Feb 15.

Authors

Mengling Cui¹, Fukun Chen², Lishi Shao¹, Chanyan Wei¹, Weihu Zhang¹, Wenmei Sun¹, Jiaping Wang¹

Affiliations

¹ Department of Radiology, Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, 650101, PR China.
² Department of Radiology, Kunming Medical University & the Third Affiliated Hospital, Kunming, Yunnan, 650101, PR China.

Abstract

Objective: This review discusses recent experimental and clinical findings related to ferroptosis, with a focus on the role of MSCs. Therapeutic efficacy and current applications of MSC-based ferroptosis therapies are also discussed.

Background: Ferroptosis is a type of programmed cell death that differs from apoptosis, necrosis, and autophagy; it involves iron metabolism and is related to the pathogenesis of many diseases, such as Parkinson's disease, cancers, and liver diseases. In recent years, the use of mesenchymal stem cells (MSCs) and MSC-derived exosomes has become a trend in cell-free therapies. MSCs are a heterogeneous cell population isolated from a diverse range of human tissues that exhibit immunomodulatory functions, regulate cell growth, and repair damaged tissues. In addition, accumulating evidence indicates that MSC-derived exosomes play an important role, mainly by carrying a variety of bioactive substances that affect recipient cells. The potential mechanism by which MSC-derived exosomes mediate the effects of MSCs on ferroptosis has been previously demonstrated. This review provides the first overview of the current knowledge on ferroptosis, MSCs, and MSC-derived exosomes and highlights the potential application of MSCs exosomes in the treatment of ferroptotic conditions. It summarizes their mechanisms of action and techniques for enhancing MSC functionality. Results obtained from a large number of experimental studies revealed that both local and systemic administration of MSCs effectively suppressed ferroptosis in injured hepatocytes, neurons, cardiomyocytes, and nucleus pulposus cells and promoted the survival and regeneration of injured organs.

Methods: We reviewed the role of ferroptosis in related tissues and organs, focusing on its characteristics in different diseases. Additionally, the effects of MSCs and MSC-derived exosomes on ferroptosis-related pathways in various organs were reviewed, and the mechanism of action was elucidated. MSCs were shown to improve the disease course by regulating ferroptosis.

Keywords: Exosomes; Ferroptosis; Glutathione peroxidase 4; Lipid peroxidation; Lipid reactive oxygen species; Mesenchymal stem cells.

Publication types

Review