Ferroptosis Profiles of Human Mesenchymal Stromal Cell Subsets at the Single-Cell Level

Xin Wen1,2, Shuai Ding2, Yujie Zhou1

  • 1Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, China Pharmaceutical University, Nanjing, China.

DNA and Cell Biology
|November 28, 2025
PubMed

Insights

Mesenchymal stromal cells (MSCs) exhibit unique ferroptosis gene profiles. Umbilical cord MSCs (UC-MSCs), particularly the C1 subset, show increased ferroptosis, impacting their clinical applications.

Area of Science:

  • Cell Biology
  • Immunology
  • Regenerative Medicine

Background:

  • Mesenchymal stromal cells (MSCs) are utilized in clinical trials for their differentiation and immunomodulatory properties.
  • Characterization of cell death pathways, specifically ferroptosis, in MSC subsets is crucial for understanding their behavior.
  • Umbilical cord-derived MSCs (UC-MSCs) are a promising cell source, but their ferroptosis profiles require detailed investigation.

Purpose of the Study:

  • To investigate the ferroptosis profiles of MSC subsets from various tissues.
  • To elucidate the role of ferroptosis in UC-MSCs, particularly the C1 subset.
  • To assess the impact of ferroptosis modulation on UC-MSC populations.

Main Methods:

  • Analysis of differentially expressed ferroptotic genes in MSC subsets from adipose, bone marrow, dermis, and umbilical cord tissues.
  • Assessment of ferroptosis levels and sensitivity in UC-MSC subsets.
  • Treatment of UC-MSCs with ferroptosis inducers (Erastin) and inhibitors (Fer-1) during expansion.

Main Results:

  • Unique ferroptotic gene expression patterns were identified across different MSC tissue origins.
  • The C1 subset of UC-MSCs demonstrated significantly increased ferroptosis levels and sensitivity.
  • Expansion of UC-MSCs with ferroptosis modulators altered the proportion of C1 UC-MSCs.

Conclusions:

  • Ferroptosis plays a critical role in UC-MSCs, especially the C1 subset.
  • Understanding MSC ferroptosis is essential for optimizing cell-based therapies.
  • Targeting ferroptosis may allow for the selection and expansion of specific MSC subtypes for improved clinical efficacy.