Focal epilepsy human surgical samples
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA941830 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR23722451_1.fastq.gz | Fastqsanger.gz | |||
| SRR23722451_2.fastq.gz | Fastqsanger.gz | |||
| SRR23722452_1.fastq.gz | Fastqsanger.gz | |||
| SRR23722452_2.fastq.gz | Fastqsanger.gz | |||
| SRR23722453_1.fastq.gz | Fastqsanger.gz |
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Project description:Mesial temporal lobe epilepsy (MTLE) is the most common type of focal seizure disorder. In MTLE, seizures typically originate from a sclerotic hippocampus. Approximately one-third of patients do not respond to anti-seizure drugs and have few effective therapeutic options. Surgery to resect or ablate the affected temporal lobe is one such option, but it is not indicated or adequate for all individuals and can have adverse effects. Here, we report the development of an alternative cell therapy strategy for drug-resistant MTLE. The cell therapeutic is derived from a clinical-grade human embryonic stem cell line, and composed of cryopreserved post-mitotic medial ganglionic eminence (MGE)-type GABAergic inhibitory neurons of a predominantly pallial interneuron lineage. Single-dose intrahippocampal delivery of cryopreserved human pallial interneurons in a chronic mouse model of drug-resistant MTLE resulted in consistent and stable suppression of mesiotemporal seizures, with most animals becoming seizure-free. The grafted human interneurons distributed locally, matured, and persisted in the sclerotic hippocampus throughout the 8.5-month study. Pathological hallmarks of MTLE, such as hippocampal granule cell dispersion and sclerosis, were significantly reduced, and epileptic animal survival rates increased, after administration of the human interneurons. Suppression of seizure activity and amelioration of neuropathology were dose-dependent and suggested a broad therapeutic dosing range. No ectopic tissue or teratoma formation was detected after cell transplantation. Furthermore, behavioral abnormalities were not observed at any dose on a battery of assays. These findings support further development of human pallial MGE-type GABAergic interneuron cell therapy for the treatment of drug-resistant focal epilepsies.
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Project description:Surgical samples have long been used as important subjects for cancer research. In accordance with an increase of neoadjuvant therapy, biopsy samples have recently become imperative for cancer transcriptome. On the other hand, both biopsy and surgical samples are available for expression profiling for predicting clinical outcome by adjuvant therapy; however, it is still unclear whether surgical sample expression profiles are useful for the prediction by the use of biopsy samples because little has been done about comparative gene expression profiling between the two kinds of samples. When gene expression profiles were compared between biopsy and surgical samples, artificially induced epithelial-mesenchymal transition (aiEMT) was found in the surgical samples. This study will evoke the fundamental misinterpretation including underestimation of the prognostic evaluation power of markers by overestimation of EMT in past cancer research, and will furnish some advice for the near future as follows: 1) Understanding how long the tissues were under an ischemic condition; 2) Prevalence of biopsy samples for in vivo expression profiling with low biases on basic and clinical research; and 3) Checking cancer cell contents and normal- or necrotic-tissue contamination in biopsy samples for prevalence.
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