Density dependent regulation of human Schwann cell proliferation

Gizelda T B Casella, Raimund Wieser, Richard P. Bunge, Irene S. Margitich, Jennifer Katz, Les Olson, Patrick Wood

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Cessation of division is prerequisite for Schwann cell differentiation but regulation of this critical function is poorly understood. Heregulin/forskolin-induced growth of human Schwann cells (HSCs) in vitro was found to be strongly regulated by cell density and thus could model some aspects of negative growth-regulation in vivo. To better understand this phenomenon, the production of an autocrine growth-inhibitor and the role of contact-inhibition were investigated. The possible involvement of two membrane proteins, contactinhibin (CI) and peripheral myelin protein 22 (PMP22) in regulating growth was studied. Thymidine-labeling of HSCs on collagen-coated dishes was inhibited at cell densities less than one tenth of the density at maximal growth-inhibition. Medium from high density cultures did not inhibit the thymidine-labeling of HSCs at low density, a result that argues against the production of a soluble inhibitor. The expression of CI and PMP22 in nerve and HSCs, and the effect of a function-blocking antibody to CI on HSC growth, were determined. CI was detected in fresh nerve by western blotting, and could easily be detected by immunocytochemistry in cultured HSCs by five days and for several weeks thereafter. Twenty-four hour treatment with anti-CI antibody did not increase the thymidine-labeling of HSCs at any density but a significant increase in HSC number was observed in cultures treated with anti-CI for 20 days. This increase was not related to decreased cell death. PMP22, unlike other myelin proteins, was not down-regulated after nerve dissociation and by seven days nearly all HSCs were PMP22 positive. These results provide evidence for a contact-mediated mechanism of growth-regulation in HSCs and suggest that CI is involved in this mechanism. (C) 2000 Wiley-Liss, Inc.

Original languageEnglish
Pages (from-to)165-177
Number of pages13
JournalGLIA
Volume30
Issue number2
DOIs
StatePublished - Apr 25 2000

Fingerprint

Schwann Cells
Cell Proliferation
Myelin Proteins
Growth
Thymidine
Cell Count
Neuregulin-1
Contact Inhibition
Growth Inhibitors
Blocking Antibodies
Colforsin
Cell Differentiation
Anti-Idiotypic Antibodies
Membrane Proteins
Cell Death
Collagen
Western Blotting
Immunohistochemistry

Keywords

  • Cell density
  • Contactinhibin
  • Human cell culture
  • Inhibitory factor
  • Neuregulin
  • Neuroglia
  • Peripheral myelin
  • PMP22
  • Proliferation
  • Schwann cells

ASJC Scopus subject areas

  • Immunology

Cite this

Casella, G. T. B., Wieser, R., Bunge, R. P., Margitich, I. S., Katz, J., Olson, L., & Wood, P. (2000). Density dependent regulation of human Schwann cell proliferation. GLIA, 30(2), 165-177. https://doi.org/10.1002/(SICI)1098-1136(200004)30:2<165::AID-GLIA6>3.0.CO;2-L

Density dependent regulation of human Schwann cell proliferation. / Casella, Gizelda T B; Wieser, Raimund; Bunge, Richard P.; Margitich, Irene S.; Katz, Jennifer; Olson, Les; Wood, Patrick.

In: GLIA, Vol. 30, No. 2, 25.04.2000, p. 165-177.

Research output: Contribution to journalArticle

Casella, GTB, Wieser, R, Bunge, RP, Margitich, IS, Katz, J, Olson, L & Wood, P 2000, 'Density dependent regulation of human Schwann cell proliferation', GLIA, vol. 30, no. 2, pp. 165-177. https://doi.org/10.1002/(SICI)1098-1136(200004)30:2<165::AID-GLIA6>3.0.CO;2-L
Casella GTB, Wieser R, Bunge RP, Margitich IS, Katz J, Olson L et al. Density dependent regulation of human Schwann cell proliferation. GLIA. 2000 Apr 25;30(2):165-177. https://doi.org/10.1002/(SICI)1098-1136(200004)30:2<165::AID-GLIA6>3.0.CO;2-L
Casella, Gizelda T B ; Wieser, Raimund ; Bunge, Richard P. ; Margitich, Irene S. ; Katz, Jennifer ; Olson, Les ; Wood, Patrick. / Density dependent regulation of human Schwann cell proliferation. In: GLIA. 2000 ; Vol. 30, No. 2. pp. 165-177.
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