Human neural stem cell transplantation reduces spontaneous recurrent seizures following pilocarpine-induced status epilepticus in adult rats

Chu, Kon; Kim, Manho; Jung, Keun Hwa; Jeon, Daejong; Kim, Ju-Hyun; Jeong, Seonghun; Kim, Seung Up; Lee, Sang Kun; Shin, Hee Sup; Roh, Jae Kyu

doi:10.1016/j.brainres.2004.07.045

Cited by 120 publications

(89 citation statements)

References 39 publications

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“…Human neural stem cells transplanted into the pilocarpine-induced rat model of TLE differentiate into GABA-IR interneurons in the damaged hippocampus. Such grafted cells also reduce generalized convulsive seizure frequency and severity [88] .…”

Section: Cell Therapymentioning

confidence: 97%

Dysfunction of hippocampal interneurons in epilepsy

Liu

et al. 2014

Neurosci. Bull.

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Gamma-amino-butyric acid (GABA)-containing interneurons are crucial to both development and function of the brain. Down-regulation of GABAergic inhibition may result in the generation of epileptiform activity. Loss, axonal sprouting, and dysfunction of interneurons are regarded as mechanisms involved in epileptogenesis. Recent evidence suggests that network connectivity and the properties of interneurons are responsible for excitatory-inhibitory neuronal circuits. The balance between excitation and inhibition in CA1 neuronal circuitry is considerably altered during epileptic changes. This review discusses interneuron diversity, the causes of interneuron dysfunction in epilepsy, and the possibility of using GABAergic neuronal progenitors for the treatment of epilepsy.

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Section: Cell Therapymentioning

confidence: 97%

Dysfunction of hippocampal interneurons in epilepsy

Liu

et al. 2014

Neurosci. Bull.

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“…NPCs injected systemically into healthy animals were in fact never found in the CNS, while exclusively accumulating (and persisting only for a short period) in peripheral organs (Pluchino et al, 2003). Specific homing of transplanted NPCs has been shown, so far, in experimental brain stroke (Chu et al, 2003;Lindvall and Kokaia, 2011), SCI (Takeuchi et al, 2007), epilepsy (Chu et al, 2004;Hattiangady et al, 2008), HD (Lee et al, 2006), and glioblastoma (Aboody et al, 2000;Ahmed et al, 2011).…”

Section: Homing and Extravasationmentioning

confidence: 99%

How stem cells speak with host immune cells in inflammatory brain diseases

Pluchino

Cossetti

2013

Glia

111

109

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Advances in stem cell biology have raised great expectations that diseases and injuries of the central nervous system (CNS) may be ameliorated by the development of non-hematopoietic stem cell medicines. Yet, the application of adult stem cells as CNS therapeutics is challenging and the interpretation of some of the outcomes ambiguous. In fact, the initial idea that stem cell transplants work only via structural cell replacement has been challenged by the observation of consistent cellular signaling between the graft and the host. Cellular signaling is the foundation of coordinated actions and flexible responses, and arises via networks of exchanging and interacting molecules that transmit patterns of information between cells. Sustained stem cell graft-to-host communication leads to remarkable trophic effects on endogenous brain cells and beneficial modulatory actions on innate and adaptive immune responses in vivo, ultimately promoting the healing of the injured CNS. Among a number of adult stem cell types, mesenchymal stem cells (MSCs) and neural stem/precursor cells (NPCs) are being extensively investigated for their ability to signal to the immune system upon transplantation in experimental CNS diseases. Here, we focus on the main cellular signaling pathways that grafted MSCs and NPCs use to establish a therapeutically relevant cross talk with host immune cells, while examining the role of inflammation in regulating some of the bidirectionality of these communications. We propose that the identification of the players involved in stem cell signaling might contribute to the development of innovative, high clinical impact therapeutics for inflammatory CNS diseases.

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“…This study was important for a number of reasons. First, it extended the anticonvulsant effect of transplanted cells from days to several weeks (reported in other studies 51,53,55 ) to several months to 1 year, by pretreatment of the tissue with growth factors and antiapoptotic agents. Second, it demonstrated that, in a model of SE that produces hippocampal and extrahippocampal damage (also seen in clinical cases of TLE 66 ), transplanting exclusively into the hippocampus could block seizure occurrence.…”

Section: Fetal and Embryonic Tissue Transplantsmentioning

confidence: 90%

“…21 Immortalized neural cell lines (both neuronal and glial) engineered to overexpress glutamate decarboxylase (GAD) and GABA have been shown to suppress seizures in several seizure model. 50 -54 More recently, rodent embryonic stem cells (SCs) that overproduce adenosine 36 and human embryonic SCs that can differentiate into GABAergic neurons 55 have been shown to suppress seizures. Some reports indicate that synaptic integration within the host is not required for seizure relief, 56 and that anticonvulsant effects can be achieved by raising GABA concentrations focally 57 (at least in the short term), but others stress the need for synaptic integration and brain repair for effective seizure control.…”

Section: Transplantation In Tlementioning

confidence: 99%

“…Some investigators have argued that the majority of transplant recipients in clinical settings will in fact be older, intractable patients suffering from neurodegenerative processes 88 and that therefore transplantation studies in aged rats should be explored. 101 A study by Chu et al 55 is notable for reported reduction of recurrent spontaneous seizures, cell dispersion into areas of damage, and enhanced GABAergic inhibition in the damaged hippocampus after transplantation of NSC. In that study, animals experienced 1 hour of continuous seizure induced by LiPC SE.…”

Section: Stem/progenitor Cell Transplantsmentioning

confidence: 99%

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Transplantation of GABA-Producing Cells for Seizure Control in Models of Temporal Lobe Epilepsy

Thompson

2009

Neurotherapeutics

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Summary:A high percentage of patients with temporal lobe epilepsy (TLE) are refractory to conventional pharmacotherapy. The progressive neurodegenerative processes associated with a lifetime of uncontrolled seizures mandate the development of alternative approaches to treat this disease. Transplantation of inhibitory cells has been suggested as a potential therapeutic strategy to achieve seizure suppression in humans with intractable TLE. Preclinical investigations over 20 years have demonstrated that multiple cell types from several sources can produce anticonvulsant, and antiepileptogenic, effects in animal models of TLE. Transplanting GABA-producing cells, in particular, has been shown to reduce seizures in several well-established models. This review addresses experimentation using different sources of transplantable GABAergic cells, highlighting progress with fetal tissue, neural cell lines, and stem cells. Regardless of the source of the GABAergic cells used in seizure studies, common challenges have emerged. Several variables influence the anticonvulsant potential of GABA-producing cells. For example, tissue availability, graft survival, immunogenicity, tumorigenicity, and varying levels of cell migration, differentiation, and integration into functional circuits and the microenvironment provided by sclerotic tissue all contribute to the efficacy of transplanted cells. The challenge of understanding how all of these variables work in concert, in a disease process that has no well-established etiology, suggests that there is still much basic research to be done before rational cell-based therapies can be developed for TLE.

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Human neural stem cell transplantation reduces spontaneous recurrent seizures following pilocarpine-induced status epilepticus in adult rats

Cited by 120 publications

References 39 publications

Dysfunction of hippocampal interneurons in epilepsy

Dysfunction of hippocampal interneurons in epilepsy

How stem cells speak with host immune cells in inflammatory brain diseases

Transplantation of GABA-Producing Cells for Seizure Control in Models of Temporal Lobe Epilepsy

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