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Hemangioblastoma Stromal Cells Show Committed Stem Cell Phenotype

Published online by Cambridge University Press:  02 December 2014

Cassandra M. Welten ,
Emily C. Keats ,
Lee-Cyn Ang  and
Zia A. Khan
Cassandra M. Welten
Affiliation:
Department of Pathology, London Health Sciences Centre
Emily C. Keats
Affiliation:
Department of Pathology, London Health Sciences Centre
Lee-Cyn Ang
Affiliation:
Department of Pathology, London Health Sciences Centre The University of Western Ontario, Division of Neuropathology, London Health Sciences Centre
Zia A. Khan*
Affiliation:
Department of Pathology, London Health Sciences Centre Metabolism and Diabetes Research Program, Lawson Health Research Institute, London, ON Canada
*
4011 Dental Sciences Building, 1151 Richmond Street, London, Ontario, N6A 5C1, Canada. Email: zia.khan@schulich.uwo.ca
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Abstract

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Background:

Hemangioblastomas are benign vascular tumors of the central nervous system that occur sporadically or in association with von Hippel-Lindau disease. These tumors are characteristically composed of a dense capillary network with intervening stromal/interstitial cells. To date, the histogenesis of hemangioblastoma remains unclear. We hypothesize that hemangioblastomas arise from a defective mesodermal stem cell, which gives rise to the atypical vasculature.

Methods:

To test our hypothesis, we have characterized the cellular composition of hemangioblastomas by immunophenotyping pluripotent and committed stem cells and vascular endothelial cells.

Results:

Our findings show that hemangioblastoma endothelial cells are positive for CD133, a stem and progenitor cell marker. Vascular endothelial cells also expressed nuclear Oct4. In addition to the endothelium, both CD133 and Oct4 were present in stromal and perivascular cells. Interestingly, neither the endothelium nor the stromal cells expressed Sox2 or Nanog suggesting a committed stem cell phenotype.

Conclusions:

From these findings, we believe that hemangioblastoma stromal cells are committed stem cells producing both vascular cell types. The findings also show an unusual CD133-positive endothelial phenotype in hemangioblastoma.

Résumé

RÉSUMÉContexte:

Les hémangioblastomes sont des tumeurs vasculaires bénignes du système nerveux central qui surviennent sporadiquement ou en association à la maladie de von Hippel-Lindau. Ces tumeurs sont composées d'un réseau capillaire dense intercalé de cellules stromales/interstitielles. À ce jour, l'histogenèse de l'hémangioblastome demeure obscure. Nous émettons l'hypothèse que les hémangioblastomes proviennent de cellules souches mésodermiques défectueuses qui donnent naissance à un réseau vasculaire anormal.

Méthode:

Nous avons caractérisé la composition cellulaire d'hémangioblastomes par immunophénotypage de cellules souches pluripotentes et de cellules souches commises ainsi que de cellules vasculaires endothéliales afm de vérifier notre hypothèse de travail.

Résultats:

Nos observations démontrent que les cellules endothéliales de l'hémangioblastome sont positives pour CD133, un marqueur des cellules souches et des cellules progénitrices. Les cellules endothéliales vasculaires exprimaient également l'Oct4 au niveau du noyau. En plus d'être présent dans l'endothélium, CD133 et Oct4 étaient également présents dans les cellules stromales et périvasculaires. À noter que ni l'endothélium ni les cellules stromales n'exprimaient Sox2 ou Nanog, ce qui suggère un phénotype de cellules souches commises.

Conclusions:

Ces observations nous laissent croire que les cellules stromales de l'hémangioblastome sont des cellules souches commises qui produisent les deux types de cellules vasculaires. Nous avons également observé un phénotype endothélial CD133 positif inusité dans l'hémangioblastome.

Type
Original Articles
Information
Canadian Journal of Neurological Sciences , Volume 39 , Issue 6 , November 2012 , pp. 821 - 827
Copyright
Copyright © The Canadian Journal of Neurological 2012

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