Dataset Information

CRISPR/Cas9 Edited sRAGE-MSCs Protect Neuronal Death in Parkinsons Disease Model.

ABSTRACT:

Background and objectives

Parkinsons disease (PD) is a fatal and progressive degenerative disease of the nervous system. Until recently, its promising treatment and underlying mechanisms for neuronal death are poorly understood. This study was investigated to identify the molecular mechanism of neuronal death in the substantia nigra and corpus striatum of PD.

Methods

The soluble RAGE (sRAGE) secreting Umbilical Cord Blood-derived Mesenchymal Stem Cell (UCB-MSC) was generated by gene editing method using clustered regularly interspaced short palindromic repeats/CRISPR associated protein 9 (CRISPR/Cas9). These cells were transplanted into Corpus Striatum of rotenone-induced PD animal models then behavioral test, morphological analysis, and immunohistochemical experiments were performed to determine the neuronal cell death and recovery of movement.

Results

The neuronal cell death in Corpus Striatum and Substantia Nigra was dramatically reduced and the movement was improved after sRAGE secreting UCB-MSC treatment in PD mice by inhibition of RAGE in neuronal cells.

Conclusions

We suggest that sRAGE secreting UCB-MSC based therapeutic approach could be a potential treatment strategy for neurodegenerative disease including PD.

SUBMITTER: Lee J

PROVIDER: S-EPMC6457706 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Publications

CRISPR/Cas9 Edited sRAGE-MSCs Protect Neuronal Death in Parkinsons Disease Model.

Lee Jaesuk J Bayarsaikhan Delger D Arivazhagan Roshini R Park Hyejung H Lim Byungyoon B Gwak Peter P Jeong Goo-Bo GB Lee Jaewon J Byun Kyunghee K Lee Bonghee B

International journal of stem cells 20190301 1

<h4>Background and objectives</h4>Parkinsons disease (PD) is a fatal and progressive degenerative disease of the nervous system. Until recently, its promising treatment and underlying mechanisms for neuronal death are poorly understood. This study was investigated to identify the molecular mechanism of neuronal death in the substantia nigra and corpus striatum of PD.<h4>Methods</h4>The soluble RAGE (sRAGE) secreting Umbilical Cord Blood-derived Mesenchymal Stem Cell (UCB-MSC) was generated by g ...[more]

PMID: 30836725

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Project description:Gene editing in large animal models for future applications in translational medicine and food production must be deeply investigated for an increase of knowledge. The mitochondrial transcription factor A (TFAM) is a member of the HMGB subfamily that binds to mtDNA promoters. This gene maintains mtDNA, and it is essential for the initiation of mtDNA transcription. Lately, we generated a new cell line through the disruption of the TFAM gene in bovine fibroblast cells by CRISPR/Cas 9 technology. We showed that the CRISPR/Cas9 design was efficient through the generation of heterozygous mutant clones. In this context, once this gene regulates the mtDNA replication specificity, the study aimed to determine if the post-edited cells are capable of in vitro maintenance and assess if they present changes in mtDNA copies and mitochondrial membrane potential after successive passages in culture. The post-edited cells were expanded in culture, and we performed a growth curve, doubling time, cell viability, mitochondrial DNA copy number, and mitochondrial membrane potential assays. The editing process did not make cell culture unfeasible, even though cell growth rate and viability were decreased compared to control since we observed the cells grow well when cultured in a medium supplemented with uridine and pyruvate. They also exhibited a classical fibroblastoid appearance. The RT-qPCR to determine the mtDNA copy number showed a decrease in the edited clones compared to the non-edited ones (control) in different cell passages. Cell staining with Mitotracker Green and red suggests a reduction in red fluorescence in the edited cells compared to the non-edited cells. Thus, through characterization, we demonstrated that the TFAM gene is critical to mitochondrial maintenance due to its interference in the stability of the mitochondrial DNA copy number in different cell passages and membrane potential confirming the decrease in mitochondrial activity in cells edited in heterozygosis.

Dataset Information

CRISPR/Cas9 Edited sRAGE-MSCs Protect Neuronal Death in Parkinsons Disease Model.

Background and objectives

Methods

Results

Conclusions

Publications

CRISPR/Cas9 Edited sRAGE-MSCs Protect Neuronal Death in Parkinsons Disease Model.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

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Dataset Information

CRISPR/Cas9 Edited sRAGE-MSCs Protect Neuronal Death in Parkinsons Disease Model.

Background and objectives

Methods

Results

Conclusions

Publications

CRISPR/Cas9 Edited sRAGE-MSCs Protect Neuronal Death in Parkinsons Disease Model.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

CRISPR/Cas9 Edited sRAGE-MSCs Protect Neuronal Death in Parkinsons Disease Model.

CRISPR/Cas9 Edited sRAGE-MSCs Protect Neuronal Death in Parkinsons Disease Model.