Transplantation of tauroursodeoxycholic acid-inducing M2-phenotype macrophages promotes an anti-neuroinflammatory effect and functional recovery after spinal cord injury in rats

Cell Prolif. 2021 Jun;54(6):e13050. doi: 10.1111/cpr.13050. Epub 2021 May 7.

Abstract

Objectives: In this study, we study the transplantation of tauroursodeoxycholic acid (TUDCA)-induced M2-phenotype (M2) macrophages and their ability to promote anti-neuroinflammatory effects and functional recovery in a spinal cord injury (SCI) model.

Methods: To this end, compared to the granulocyte-macrophage colony-stimulating factor (GM-CSF), we evaluated whether TUDCA effectively differentiates bone marrow-derived macrophages (BMDMs) into M2 macrophages.

Results: The M2 expression markers in the TUDCA-treated BMDM group were increased more than those in the GM-CSF-treated BMDM group. After the SCI and transplantation steps, pro-inflammatory cytokine levels and the mitogen-activated protein kinase (MAPK) pathway were significantly decreased in the TUDCA-induced M2 group more than they were in the GM-CSF-induced M1 group and in the TUDCA group. Moreover, the TUDCA-induced M2 group showed significantly enhanced tissue volumes and improved motor functions compared to the GM-CSF-induced M1 group and the TUDCA group. In addition, biotinylated dextran amine (BDA)-labelled corticospinal tract (CST) axons and neuronal nuclei marker (NeuN) levels were increased in the TUDCA-induced M2 group more than those in the GM-CSF-induced M1 group and the TUDCA group.

Conclusions: This study demonstrates that the transplantation of TUDCA-induced M2 macrophages promotes an anti-neuroinflammatory effect and motor function recovery in SCI. Therefore, we suggest that the transplantation of TUDCA-induced M2 macrophages represents a possible alternative cell therapy for SCI.

Keywords: bone marrow-derived macrophages; neuroinflammation; spinal cord injuries; tauroursodeoxycholic acid; transplantation.

MeSH terms

  • Animals
  • Cells, Cultured
  • Female
  • Inflammation / metabolism
  • Inflammation / physiopathology
  • Inflammation / therapy
  • Macrophages / metabolism
  • Macrophages / transplantation*
  • Rats
  • Rats, Sprague-Dawley
  • Recovery of Function
  • Spinal Cord Injuries / metabolism
  • Spinal Cord Injuries / physiopathology
  • Spinal Cord Injuries / therapy*
  • Taurochenodeoxycholic Acid / metabolism*

Substances

  • Taurochenodeoxycholic Acid
  • ursodoxicoltaurine