Effects of Schwann cell secreted factors on PC12 cell neuritogenesis and surviva

[Guest guest]

J Neurobiol. 2005 Apr;63(1):29-48.

Effects of Schwann cell secreted factors on PC12 cell neuritogenesis

and survival.

Bampton ET, JS.

Department of Human Anatomy and Genetics, University of Oxford,

Oxford OX1 3QX, United Kingdom.

We have used PC12 cells to examine the effects of factors secreted by

Schwann cells that promote cell survival and neurite outgrowth, and

hence are likely candidates for promoting neuronal regeneration.

RT-PCR showed that primary Schwann cells produced a range of

neurotrophins, excluding NT3, but this profile was different from

either of two cell lines SCTM41 or PVGSCSV40T, or forskolin-expanded

Schwann cells. The effects of Schwann cell conditioned media on

neurite outgrowth was tested against a range of factors, and showed

clear neuritogenic effects.

Of the factors tested, only NGF had a significant response on

neuritogenesis. Western blotting for neurofilaments showed that

primary Schwann cells induced a strong response close to that of NGF.

The Trk tyrosine kinase inhibitor K252a did not block the

neuritogenic effects of primary Schwann cells. In contrast, K252a

blocked both NGF and the SCTM41 cell effects. Schwann cell

conditioned media also enhanced PC12 cell survival.

Again, in contrast with NGF or SCTM41 cells, the primary Schwann cell

effect was Trk tyrosine kinase independent. The Schwann cell

conditioned medium contains a protein factor (greater than 12 kDa and

broken down by trypsin treatment) with remarkable thermal stability

(unaffected at 95 degrees C for 15 min) and the ability to bind

heparin.

Our results provide clear evidence that Schwann cells produce factors

other than those already known to stimulate a neural phenotype in

PC12 cells, and which thus have potential regeneration enhancing

effects.