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Tissue factor pathway inhibitor promotes the migration, proliferation and colonization of MSCs by regulating

Miao Li1, Dongze Qiu2, Yufan Li1

  • 1Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.

Biochemical and Biophysical Research Communications
|July 13, 2025
PubMed

Insights

Tissue factor pathway inhibitors (TFPI) enhance mesenchymal stem cell (MSC) migration and homing, improving lung injury recovery. TFPI regulates the CXCL12/CXCR4 pathway, boosting MSC colonization and function in lung injury models.

Area of Science:

  • Regenerative Medicine
  • Cell Biology
  • Pulmonary Medicine

Background:

  • Mesenchymal stem cells (MSCs) show therapeutic potential for lung injury but suffer poor retention at injury sites.
  • Tissue factor pathway inhibitors (TFPI) are known to enhance stem/progenitor cell migration and homing.
  • Combining MSCs with TFPI may overcome MSC retention limitations in lung injury treatment.

Purpose of the Study:

  • To evaluate the efficacy of combining TFPI with MSCs for treating lung injury.
  • To investigate the underlying mechanisms by which TFPI influences MSC behavior and lung repair.
  • To explore the role of the CXCL12/CXCR4 signaling pathway in TFPI-mediated MSC homing.

Main Methods:

  • Lipopolysaccharide (LPS)-induced acute lung injury (ALI) mouse model treated with rhTFPI and/or MSCs.
  • Assessment of lung histology, coagulation function, inflammatory markers (TNF-α, IL-1β), and cell colonization.
  • In vitro assays for MSC migration, viability, and proliferation; RNA sequencing for gene expression analysis.
  • Genetic manipulation of MSCs to overexpress or knockdown TFPI.

Main Results:

  • Combined rhTFPI and MSC treatment significantly improved lung injury recovery and survival rates.
  • rhTFPI enhanced MSC viability, proliferation, and migration, promoting better colonization in lung injury sites.
  • RNA sequencing revealed CXCL12 as a key upregulated gene, suggesting its involvement in the therapeutic mechanism.
  • TFPI levels modulated MSC migration, proliferation, and colonization, correlating with CXCL12/CXCR4 pathway activity.

Conclusions:

  • TFPI combined with MSCs offers a promising strategy for enhancing lung injury repair.
  • TFPI promotes MSC migration, proliferation, and homing, potentially by regulating the CXCL12/CXCR4 signaling pathway.
  • This study elucidates a novel mechanism for improving stem cell therapy efficacy in lung injury.
Keywords:
Acute lung injuryCXCL12CXCR4Mesenchymal stem cellsTissue factor pathway inhibitors

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