Publication: The histopathology of a human mesenchymal stem cell experimental tumor model: support for an hMSC origin for Ewing`s sarcoma?
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Date
2008
Authors
Burns, Jorge S. ; Abdallah, Basem M. ; Schröder, Henrik E. ; Kassem, Moustapha
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Publisher
Murcia : F. Hernández
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DOI
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info:eu-repo/semantics/article
Description
Abstract
Sarcomas display varied degrees of
karyotypic abnormality, vascularity and mesenchymal with a branching periodic acid Schiff reaction pattern.
Such clone-specific differences in host vascular response
provide novel models to explore interactions between mesenchymal stem and endothelial cells. Despite the
lack of a characteristic chromosomal translocation, the
histomorphology, biomarkers and oncogenic changes
were similar to those prevalent for Ewing’s sarcomas.
The phenotype and ontogenesis of hMSC-TERT20
tumors was consistent with the hypothesis that sarcomas
may arise from hMSC, providing a unique diploid model
for exploring human sarcoma biology.
differentiation. We have reported that a strain of
telomerized adult human bone marrow mesenchymal
stem cells (hMSC-TERT20) spontaneously evolved a
tumorigenic phenotype after long-term continuous
culture. We asked to what extent our hMSC-TERT20
derived tumors reflected events found in human
sarcomas using routine histopathological procedures.
Early versus late passage hMSC-TERT20 cultures
persistently expressed mesenchymal lineage proteins e.g.
CD105, CD44, CD99 and vimentin. However, late
passage cultures, showed increased immunohistochemical
staining for CyclinD1 and
p21WAF1/Cip1, whereas p27Kip1 staining was reduced.
Notably, spectral karyotyping showed that tumorigenic
hMSC-TERT20 cells retained a normal diploid
karyotype, with no detectable chromosome
abnormalities. Consistent with the bone-forming
potential of early passage hMSC-TERT20 cells, tumors
derived from late passage cells expressed early
biomarkers of osteogenesis. However, hMSC-TERT20
cells were heterogeneous for alpha smooth muscle actin
(ASMA) expression and one out of six hMSC-TERT20
derived single cell clones was strongly ASMA positive.
Tumors from this ASMA+ clone had distinctive vascular
qualities with hot spots of high CD34+ murine
endothelial cell density, together with CD34- regions
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