Tissue Eng Regen Med.  2025 Feb;22(2):167-180. 10.1007/s13770-024-00690-w.

Regenerative Functions of Regulatory T Cells and Current Strategies Utilizing Mesenchymal Stem Cells in Immunomodulatory Tissue Regeneration

• Ahn J
• Kim B
• Bello AB
• Moon JJ
• Arai Y
• Lee SH

• KMID: 2564703
• DOI: http://doi.org/10.1007/s13770-024-00690-w

Abstract

BACKGROUND
Regulatory T cells (Tregs) are essential for maintaining immune homeostasis and facilitating tissue regeneration by fostering an environment conducive to tissue repair. However, in damaged tissues, excessive inflammatory responses can overwhelm the immunomodulatory capacity of Tregs, compromising their functionality and potentially hindering effective regeneration. Mesenchymal stem cells (MSCs) play a key role in enhancing Treg function. MSCs enhance Treg activity through indirect interactions, such as cytokine secretion, and direct interactions via membrane proteins.
METHODS
This review examines the regenerative functions of Tregs across various tissues, including bone, cartilage, muscle, and skin, and explores strategies to enhance Treg functionality using MSCs. Advanced techniques, such as the overexpression of relevant genes in MSCs, are highlighted for their potential to further enhance Treg function. Additionally, emerging technologies utilizing extracellular vesicles (EVs) and cell membrane-derived vesicles derived from MSCs offer promising alternatives to circumvent the potential side effects associated with live cell therapies. This review proposes approaches to enhance Treg function and promote tissue regeneration and also outlines future research directions.
RESULTS
AND CONCLUSION: This review elucidates recent technological advancements aimed at enhancing Treg function using MSCs and examines their potential to improve tissue regeneration efficiency.

Keyword

Regulatory T cells; Immunomodulatory tissue regeneration; Mesenchymal stem cells; Extracellular vesicles; Cell membrane-based vesicles