Mesenchymal Stromal/Stem Cells Know Best:The Remarkable Complexities of Its InteractionsWith Polymorphonuclear Neutrophils

Li Tzu Wang, Wei Lee, Ko Jiunn Liu, Huey Kang Sytwu, Men Luh Yen, B. Linju Yen

Research output: Contribution to journalReview articlepeer-review

1 Citation (Scopus)

Abstract

Polymorphonuclear neutrophils (PMNs), the predominant immune cell type in humans, have long been known as first-line effector cells against bacterial infections mainly through phagocytosis and production of reactive oxygen species (ROS). However, recent research has unveiled novel and pivotal roles of these abundant but short-lived granulocytes in health and disease. Human mesenchymal stromal/stem cells (MSCs), renowned for their regenerative properties and modulation of T lymphocytes from effector to regulatory phenotypes, exhibit complex and context-dependent interactions with PMNs. Regardless of species or source, MSCs strongly abrogate PMN apoptosis, a critical determinant of PMN function, except if PMNs are highly stimulated. MSCs also have the capacity to fine-tune PMN activation, particularly in terms of CD11b expression and phagocytosis. Moreover, MSCs can modulate numerous other PMN functions, spanning migration, ROS production, and neutrophil extracellular trap (NET) formation/NETosis, but directionality is remarkably dependent on the underlying context: in normal nondiseased conditions, MSCs enhance PMN migration and ROS production, whereas in inflammatory conditions, MSCs reduce both these functions and NETosis. Furthermore, the state of the MSCs themselves, whether isolated from diseased or healthy donors, and the specific secreted products and molecules, can impact interactions with PMNs; while healthy MSCs prevent PMN infiltration and NETosis, MSCs isolated from patients with cancer promote these functions. This comprehensive analysis highlights the intricate interplay between PMNs and MSCs and its profound relevance in healthy and pathological conditions, shedding light on how to best strategize the use of MSCs in the expanding list of diseases with PMN involvement.

Original languageEnglish
Pages (from-to)403-415
Number of pages13
JournalStem Cells
Volume42
Issue number5
DOIs
Publication statusPublished - May 2024

Keywords

  • : polymorphonuclear neutrophils
  • apoptosis
  • CD11b
  • mesenchymal stromal/stem cells
  • migration
  • NETosis
  • phagocytosis
  • reactive oxygen species

ASJC Scopus subject areas

  • General Medicine

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