Interaction of NG2(+) glial progenitors and microglia/macrophages from the injured spinal cord

Glia. 2010 Mar;58(4):410-22. doi: 10.1002/glia.20932.

Abstract

Spinal cord contusion produces a central lesion surrounded by a peripheral rim of residual white matter. Despite stimulation of NG2(+) progenitor cell proliferation, the lesion remains devoid of normal glia chronically after spinal cord injury (SCI). To investigate potential cell-cell interactions of the predominant cells in the lesion at 3 days after injury, we used magnetic activated cell sorting to purify NG2(+) progenitors and OX42(+) microglia/macrophages from contused rat spinal cord. Purified NG2(+) cells from the injured cord grew into spherical masses when cultured in defined medium with FGF2 plus GGF2. The purified OX42(+) cells did not form spheroids and significantly reduced sphere growth by NG2(+) cells in co-cultures. Conditioned medium from these OX42(+) cells, unlike that from normal peritoneal macrophages or astrocytes also inhibited growth of NG2(+) cells, suggesting inhibition by secreted factors. Expression analysis of freshly purified OX42(+) cells for a panel of six genes for secreted factors showed expression of several that could contribute to inhibition of NG2(+) cells. Further, the pattern of expression of four of these, TNFalpha, TSP1, TIMP1, MMP9, in sequential coronal tissue segments from a 2 cm length of cord centered on the injury epicenter correlated with the expression of Iba1, a marker gene for OX42(+) cells, strongly suggesting a potential regional influence by activated microglia/macrophages on NG2(+) cells in vivo after SCI. Thus, the nonreplacement of lost glial cells in the central lesion zone may involve, at least in part, inhibitory factors produced by microglia/macrophages that are concentrated within the lesion.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens / metabolism*
  • Astrocytes / physiology
  • Calcium-Binding Proteins / metabolism
  • Cells, Cultured
  • Coculture Techniques
  • Culture Media, Conditioned
  • Female
  • Macrophages / physiology*
  • Matrix Metalloproteinase 9 / metabolism
  • Microfilament Proteins
  • Microglia / physiology*
  • Neuroglia / physiology*
  • Proteoglycans / metabolism*
  • Rats
  • Spinal Cord Injuries / physiopathology*
  • Stem Cells / physiology*
  • Thrombospondin 1 / metabolism
  • Tissue Inhibitor of Metalloproteinase-1 / metabolism
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Aif1 protein, rat
  • Antigens
  • Calcium-Binding Proteins
  • Culture Media, Conditioned
  • Microfilament Proteins
  • Proteoglycans
  • Thrombospondin 1
  • Tissue Inhibitor of Metalloproteinase-1
  • Tumor Necrosis Factor-alpha
  • chondroitin sulfate proteoglycan 4
  • Matrix Metalloproteinase 9