Assessing the efficacy of endoscopic office olfactory biopsy sites to produce neural progenitor cell cultures for the study of neuropsychiatric disorders

Abstract

Introduction The olfactory region is capable of continuous neurogenesis. Situated on the cribriform plate and segments of the superior septum and both superior and middle turbinates, it is accessible through office-based biopsy and can be used to generate neural progenitor cells to study molecular abnormalities associated with neuropsychiatric disorders. The purpose of the study was to evaluate the efficacy of the endoscopic office olfactory biopsy from middle turbinate and superior-posterior septum to produce the neural progenitor cells. Methods Endoscopic office-based biopsy samples were collected and cultured neuronal cells derived from olfactory neuroepithelium (CNON) were established from 40 healthy individuals and 40 schizophrenia patients. All patients underwent biopsies of both the middle turbinate and the superior-posterior septum. Specific culture conditions promoted the growth of neural progenitor cells from these biopsy sites. CNON cultures were established from such outgrowing neuronal cells. The study was IRB approved and informed consent was obtained. Results Cultures were successfully developed from 98.8% of participants. No complications were observed. The single, unsuccessful specimen failed to grow any cell types due to tissue mishandling. Overall, we have observed no significant difference in the effectiveness of biopsy from middle turbinate and superior-posterior septum to produce neural progenitor cells. Conclusions The middle turbinate biopsies contain viable neural progenitor cells capable of generating neuronal cell cultures. Thus technically more simple biopsy of the middle turbinate can be used to propagate neural progenitor cells.

Analysis of Gene Expression Variance in Schizophrenia Using Structural Equation Modeling

“…Several lines of evidence point to neurodevelopment as playing a primary role in etiology of the disease (Weinberger, 1987; Raedler et al, 1998; Lewis and Levitt, 2002). To elucidate neurodevelopmental aspects of SCZ mechanisms we studied gene expression profiles in CNON cells derived from SCZ patients and healthy individuals, a suitable experimental model to analyze the neurodevelopment processes (Evgrafov et al, 2006, 2017; Wrobel et al, 2013). SCZ-related genes that differ between SCZ and control groups in the mean expression levels have been identified from these data (Evgrafov et al, 2017).…”

“…The details of biopsy and cell cultivation were described previously (Evgrafov et al, 2006; Wrobel et al, 2013). RNA libraries extracted from cells were prepared and sequenced on HiSeq2000 (Illumina) as previously described (Evgrafov et al, 2017).…”

“…Because SCZ can be considered a neurodevelopmental disorder (Weinberger, 1987; Raedler et al, 1998; Lewis and Levitt, 2002; Alexander-Bloch et al, 2014), the use of port-mortem samples may not necessarily accurately capture the alterations in neurodevelopmental processes important in SCZ, but rather the consequences of these changes in terminally-differentiated cells. An alternative is to use cultured patient-derived neural progenitor cells, such as those derived from olfactory neuroepithelium (CNON; Wrobel et al, 2013), whereby neurodevelopmental changes can be modeled; environmental effects that are a component of post-mortem tissue samples can be reduced; and conditions can be standardized across samples. We analyzed the gene expression profiles in CNON cells from SCZ patients and control individuals to study alterations in gene expression reflective of the potential neurodevelopmental aspects of the disease.…”

The Olfactory Neural Epithelium As a Tool in Neuroscience

“…OE tissue was conventionally obtained by punch biopsy through nasal endoscopy [3]. In contrast, a newly developed brushing technique allows a quicker and less invasive biopsy minimizing or avoiding the use of local anesthesia.…”

Gene expression in patient-derived neural progenitors implicates WNT5A signaling in the etiology of schizophrenia

“…Here we present a study of transcriptome expression profiles using RNA-Seq (strand-specific, rRNA-depleted total RNA) in CNON lines derived from 144 SCZ and 111 control (CTL) individuals. Table 1), under approved IRB protocols (6,7). All CNON lines were cultured using the same lot of medium and cells were usually harvested after the third passage (see Online Methods).…”