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Review
. 2025 May 28;16(1):265.
doi: 10.1186/s13287-025-04360-z.

Clinical application of mesenchymal stem cells in immunosenescence: a qualitative review of their potential and challenges

Xu Wang  1   2 , Dan Guo  1 , Chengmei He  3 , Xiaoxi Wang  1 , Yi Wei  2 , Fengchun Zhang  4 , Li Wang  5 , Yanlei Yang  6
Affiliations
Review

Clinical application of mesenchymal stem cells in immunosenescence: a qualitative review of their potential and challenges

Xu Wang et al. Stem Cell Res Ther. .

Abstract

Aging leads to a gradual decline in immune function, termed immunosenescence, which significantly elevates the susceptibility to infections, cancers, and other aging-related diseases. Recent advancements have shed light on the molecular underpinnings of immune aging and pioneered novel therapeutic interventions to counteract its effects. Mesenchymal stem cells (MSCs)-a type of multipotent stromal cells with regenerative potential, low immunogenicity, and strong immunomodulatory properties-are increasingly recognized as a promising therapeutic option to reverse or alleviate immunosenescence-related dysfunction. This review systematically summarizes recent discoveries on how MSCs counteract immune aging, particularly their ability to rejuvenate aged immune cells and restore immune homeostasis. It also addresses key challenges, such as variations in MSC sources, donor variability, and the lack of standardized protocols, while proposing future directions to enhance therapeutic precision. Although preclinical and clinical studies highlight the potential of MSC-based strategies for delaying immunosenescence, critical issues remain unresolved, including long-term safety and efficacy, optimizing cell delivery systems, and elucidating context-specific mechanisms. Addressing these challenges will accelerate the development of MSC-based therapies to combat aging-associated immune decline.

Keywords: Adaptive immunity; Challenges; Immunosenescence; Inflammaging; Innate immunity; Mesenchymal stem cells.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Characteristics of immunosenescence and effects of mesenchymal stem cells on immunosenescence. BCR, B-cell receptor; MSC, mesenchymal stem cell; TCR, T-cell receptor. Aging is a complex process driven by mechanisms such as telomere shortening, DNA damage, oxidative stress, and chronic inflammation, all of which contribute to immunosenescence. This decline affects both the quantity and function of innate and adaptive immune cells to varying degrees. MSCs exert anti-inflammatory and immunomodulatory effects through direct cell-cell interactions and indirect mechanisms that counteract immunosenescence.
Fig. 2
Fig. 2
Challenges and future perspectives in the clinical application of mesenchymal stem cells (MSCs)
See this image and copyright information in PMC

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