Third trimester NG2-positive amniotic fluid cells are effective in improving repair in spinal cord injury

Exp Neurol. 2014 Apr:254:121-33. doi: 10.1016/j.expneurol.2014.01.015. Epub 2014 Jan 29.

Abstract

Spinal cord injury presents a significant therapeutic challenge since the treatments available are mostly vain. The use of stem cells to treat this condition represents a promising new therapeutic strategy; therefore, a variety of stem cell treatments have been recently examined in animal models of CNS trauma. In this work, we analyzed the effects of third trimester amniotic fluid cells in a mouse model of spinal cord injury. Among the different cultures used for transplantation, some were able to induce a significant improvement in motor recovery (cultures #3.5, #3.6 and #7.30), evaluated by means of open field free locomotion. All effective cell cultures expressed the surface marker nerve/glial antigen 2, ortholog of the human chondroitin sulfate proteoglycan 4, which is present on several types of immature progenitor cells. The improved motor functional recovery was correlated with higher myelin preservation in the ventral horn white matter and an increased vascularization in the peri-lesion area. Real-Time PCR analysis showed higher expression levels of vascular endothelial growth factor and hypoxia-inducible factor-1α mRNA two days after cells transplantation compared to PBS-treated animals, indicating that an angiogenic pathway might have been activated by these cells, possibly through the production of hepatocyte growth factor. This cytokine appears to be produced mostly in filtering organs, such as the lung, of the transplanted animals and is likely released in the blood suggesting an endocrine role of hepatocyte growth factor in targeting the injury site.

Keywords: Amniotic fluid cells; Angiogenesis; HGF; NG2; Spinal cord injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amniotic Fluid / cytology*
  • Angiogenic Proteins / genetics
  • Animals
  • Antigens / metabolism
  • Biomarkers / metabolism
  • Disease Models, Animal
  • Female
  • Hepatocyte Growth Factor / blood
  • Hepatocyte Growth Factor / genetics
  • Humans
  • Lung / cytology
  • Male
  • Mice
  • Neovascularization, Physiologic / genetics
  • Neovascularization, Physiologic / physiology
  • Pluripotent Stem Cells / cytology
  • Pluripotent Stem Cells / metabolism
  • Pluripotent Stem Cells / transplantation*
  • Pregnancy
  • Pregnancy Trimester, Third
  • Proteoglycans / metabolism
  • Recovery of Function / physiology
  • Spinal Cord / blood supply
  • Spinal Cord / pathology*
  • Spinal Cord Injuries / pathology*
  • Spinal Cord Injuries / therapy*
  • Stem Cell Transplantation / methods*
  • Treatment Outcome

Substances

  • Angiogenic Proteins
  • Antigens
  • Biomarkers
  • Proteoglycans
  • chondroitin sulfate proteoglycan 4
  • Hepatocyte Growth Factor