Balloon cells in human cortical dysplasia and tuberous sclerosis: isolation of a pathological progenitor-like cell

Abstract

Neural stem cells are present in the human post-natal brain and are important in the development of brain tumours. However, their contribution to non-neoplastic human disease is less clear. We have tested the hypothesis that malformations of cortical development contain abnormal (pathological) stem cells. Such malformations are a major cause of epilepsy. Two of the most common malformations [focal cortical dysplasia (FCD) and cortical tubers] are characterised by the presence of a population of abnormal cells known as balloon cells. The identity of these cells is unknown but one hypothesis is that they are an abnormal stem cell that contributes to the pathogenesis of the malformation. We have characterised in tissue, and isolated in culture, an undifferentiated population of balloon cells from surgical resections of FCD and cortical tubers. We show that beta1-integrin labels a sub-population of balloon cells with a stem cell phenotype and show for the first time that these cells can be isolated in vitro. We have characterised the immunohistochemical, morphological and ultrastructural features of these cells. This is the first isolation of an abnormal cell with features of a progenitor/stem cell from a non-neoplastic disease of the brain.

FCD Type II and mTOR pathway: Evidence for different mechanisms involved in the pathogenesis of dysmorphic neurons

“…Involvement of the PI3k-Akt upstream pathway has been previously suggested, particularly in BCs (Ljungberg et al, 2006;Schick et al, 2006;Schick et al, 2007;Yasin et al, 2010;Lin et al, 2015). In line with this literature, we observed pAkt and pPDK1 expression in high percentage of BCs.…”

A developmental and genetic classification for malformations of cortical development: update 2012

“…In contrast, cells from FCDI express few early proteins (Hadjivassiliou et al , 2010; Orlova et al , 2010) and those expressed are found in more superficial layers (junction of layers I and II) (Hadjivassiliou et al , 2010). Other studies (Yasin et al , 2010; Han et al , 2011) suggest that balloon cells in patients with FCDII originate from glioneuronal progenitor cells, strongly suggesting that defects of neuronal and glial specifications are important in the histogenesis of FCDII. These findings support the concept that cells of FCDII derive from radial glial progenitors (Lamparello et al , 2007) and may support the ‘dysmature cerebral developmental hypothesis’ that seizures in some forms of FCD may be the result of interactions of dysmature cells with normal postnatal ones (Cepeda et al , 2006).…”

Layer-specific gene expression in epileptogenic type II focal cortical dysplasia: normal-looking neurons reveal the presence of a hidden laminar organization

“…In addition to morphological changes (cytomegaly, abnormal dendritic arbors, and the loss of radial orientation), DNs are characterised by the aberrant expression of neuronal and glial markers with a prevalently neuronal-mature identity. BCs are also characterised by morphological anomalies such as voluminous cytoplasms, displaced nuclei and the co-expression of different mature/immature neuronal/glial markers with a prevalently glial-immature phenotype [5-7]. The lack of a clear cell-type specification may reflect alterations in normal neuronal and glial proliferation [2,8] and subsequent migration.…”