Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Supramolecular Mimic of Glial Cell Line-Derived Neurotrophic Factor and its Bioactivity on Human Dopaminergic Neurons

ABSTRACT: The cardinal motor symptoms of Parkinson´s disease (PD) are caused by the degeneration of dopaminergic neurons, making it in principle amenable to treatment by cell replacement therapy. Although this strategy has shown promise in animal models, it has not been as successful in clinical trials. One likely reason for this lack of success is the poor survival of grafted neurons. In animal models, glial cell line-derived neurotrophic factor (GDNF) increases the survival of transplanted dopaminergic neurons, but the ability of GDNF to promote survival is undoubtedly limited by its diffusion away from the graft site and its degradation. We report here on supramolecular nanofibers that display a GDNF-mimetic peptide on their surfaces. This nanostructure mimicked the biological effects of GDNF on human dopaminergic neurons by improving cell survival and promoting morphological, synaptic and electrophysiological maturation, as well as a neuroprotective effect that correlates with the upregulation of genes related to these biological processes. The GDNF nanostructures also enhanced the morphological maturation of human midbrain-like organoids. Thus, the GDNF supramolecular mimic provides a self-assembling matrix that could be delivered in the future with transplanted dopaminergic neurons to enhance their survival and maturation in vivo.

ORGANISM(S): Homo sapiens

PROVIDER: GSE253788 | GEO | 2024/07/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Viral Delivery Of GDNF Promotes Functional Integration Of Human Stem Cell Grafts In Parkinson’s Disease

Project description:Dopaminergic neurons (DAn), generated from human pluripotent stem cells (hPSC), are capable of functionally integrating following transplantation and have recently advanced to clinical trials for Parkinson’s disease (PD). However, pre-clinical studies have highlighted the low proportion of DAn within hPSC-derived grafts and their inferior plasticity compared to fetal tissue. Here we examined whether delivery of a developmentally critical protein, glial cell line-derived neurotrophic factor (GDNF), could improve graft outcomes. We tracked the response of DAn implanted into either a GDNF-rich environment, or after a delay in exposure. Early GDNF promoted survival and plasticity of non-DAn, leading to enhanced motor recovery in PD rats. Delayed exposure to GDNF promoted functional recovery through increases in DAn specification, DAn plasticity and dopamine metabolism. Transcriptional profiling revealed a role for MAPK-signalling downstream of GDNF. Collectively these results demonstrate the potential of neurotrophic gene therapy strategies to improve hPSC graft outcomes.

2020-01-06 | GSE143136 | GEO

Human iPSC-derived neural progenitor cells secreting GDNF provide protection in rodent models of ALS and retinal degeneration

Project description:Expanded populations of human fetal-derived neural progenitor cells transduced to produce GDNF (fNPC-GDNF) have now been shown to survive for over three years following injection into the human spinal cord and can provide neuroprotection in many animal models. However, low availability of starting material limits their widespread use. Human induced pluripotent stem cells (iPSCs) are an alternative, renewable cell source that can be differentiated into NPCs and transduced with GDNF (iNPC-GDNF). The goal of the current study was to characterize iNPC-GDNF cells and test their therapeutic potential and safety. Single nuclei RNA- seq showed that fNPC-GDNF and iNPC-GDNF had both overlapping and unique clusters of cells, suggesting that the two products were not identical. When transplanted into the subretinal space of a rodent model of retinal degeneration, iNPC-GDNF preserved photoreceptors and visual function. Transplantation of iNPC-GDNF into the lumbar spinal cord of a rodent model of ALS preserved motor neurons. Finally, to evaluate long-term safety and tolerability, iNPC-GDNF were transplanted into the spinal cord of athymic nude rats for 9 months. Surviving grafts secreting GDNF were found in all animals with no signs of tumor formation or cell proliferation. iNPC-GDNF survive long-term, are safe, and provide neuroprotection in models of both retinal degeneration and ALS, indicating their potential for clinical trials as a cell and gene therapy-based treatment for various neurodegenerative diseases.

2023-04-19 | GSE214210 | GEO

A Co-Culture Model of Dopaminergic and Glutamatergic Neurons Derived from Patients with Idiopathic Schizophrenia reveals a Hypodopaminergic Phenotype

Project description:To identify morphological and functional phenotypes relevant for SCZ, we generated iPSC-derived dopaminergic neurons from three healthy controls and four patient with schizophrenia. We then performed gene expression profiling analysis using data obtained from RNA-seq of four schizophrenia patients and three controls to determine significantly deregulated genes in schizophrenia dopaminergic neurons.

2024-08-27 | GSE275064 | GEO

Gene expression in spinal cord neurons grown on polyornithine or on carbon nanotube (CNT)-based substrates

Project description:Carbon nanotubes are cylindrically-shaped carbon nanostructures, made up of layers of graphene rolled onto themselves, with diameters similar to those of neuronal processes. In the last decade, CNT have been used as biocompatible growing substrates for neuronal attachment, differentiation and growth. In the perspective of new developments in tissue engineering, and in particular in spinal cord repair strategies, based on the use of CNTs, our aim is to clarify the biophysical interactions between CNTs and spinal cord neurons, studying the development of the morphological and functional characteristics of spinal neurons grown on CNT-based interfaces. In this context, we used microarrays to show whether cultured dissociated spinal neurons show a difference in gene expression when grown in control conditions (polyornithine-covered substrates) or on CNT-based substrates. Gene expression profiling was evaluated from 3 replicates each of neurons grown on nanotubes and control conditions.

2013-08-05 | E-GEOD-27212 | biostudies-arrayexpress

Supramolecular Mimic of Glial Cell Line-Derived Neurotrophic Factor and its Bioactivity on Human Dopaminergic Neurons

Project description:Supramolecular Mimic of Glial Cell Line-Derived Neurotrophic Factor and its Bioactivity on Human Dopaminergic Neurons

| PRJNA1067128 | ENA

Gene expression in spinal cord neurons grown on polyornithine or on carbon nanotube (CNT)-based substrates

2013-08-05 | GSE27212 | GEO

Elevated endogenous GDNF levels associate with schizophrenia in humans and mice

Project description:Recent studies have identified presynaptic increase in striatal dopamine as the primary dopaminergic abnormality in schizophrenia, responsible for changes in cortical dopamine function in schizophrenic individuals. However, increased dopamine synthesis and release are not recapitulated in existing mouse models, limiting studies on disease progression and potential treatments. We found that the levels of glial cell line-derived neurotrophic factor (GDNF), a strong dopamine system modulator, are increased in the cerebrospinal fluid of first episode psychosis patients. Using a novel strategy to conditionally increase endogenous gene expression, we developed a mouse model with timed elevation of endogenous GDNF. Conditional ‘Knock Up’ of endogenous GDNF expression (GDNF cKU) in the central nervous system at midgestation resulted in an increase of dopamine levels in the presynaptic compartment of nigrostriatal dopamine neurons, hypodopaminergia in the prefrontal cortex (PFC) and schizophrenia-like behavioural deficits in the mouse. RNA sequencing from the PFC revealed gene expression changes similar to those previously found in schizophrenia patients, including downregulation of dopamine receptor 2 and adenosine A2a receptor (A2AR). Treatment of mice with A2AR antagonist istradefylline partially restored striatal and cortical dopamine levels, suggesting a potential therapeutic strategy to alleviate symptoms associated with schizophrenia. Taken together, our results demonstrate that timed increase in GDNF expression is sufficient to drive schizophrenia-like molecular and behavioural phenotypes, and represents a novel model for studying schizophrenia-associated pathologies in mice.

2023-01-03 | GSE162974 | GEO

ChIP-seq of SATB1-bound regions in human ESC-derived dopaminergic (DA) neurons at different time points. ATAC-Seq and RNA-Seq of DA and cortical neurons (WT and SATB1-KO)

Project description:SATB1 is a genetic master regulator in dopaminergic neurons. We try to identify the downstream regulated genes and pathways of SATB1 in human dopaminergic and CTX neurons. The RNA-Seq experiment was performed to investigate the role of the genetic master regulator SATB1 in human dopaminergic neurons in comparison to cortical neurons. We generated a human embryonic stem cell knockout clone for SATB1 and differentiated this clone into either dopaminergic or cortical neurons. Immature dopaminergic (day 30 of differentiation), mature dopaminergic (day 50 of differentiation) and mature cortical neurons (day 30 of differentiation) were subsequently subjected to RNA-Seq. We compared wild type and SATB1-KO neurons at the afore mentioned time points, to characterize the regulatory role of SATB1 in the different neuron subtypes.

2019-09-20 | E-MTAB-5965 | biostudies-arrayexpress

Biomimetic strategy for cartilage formation: synergy of stem cell micro-aggregates and supramolecular peptide nanofibers

Project description:Biomimetic strategy for cartilage formation: synergy of stem cell micro-aggregates and supramolecular peptide nanofibers

| PRJNA552994 | ENA

Direct reprogramming of human fibroblasts to expandable induced dopaminergic neuronal progenitors for Parkinson’s disease therapy [Array]

Project description:Personalized cell therapy is being explored as promising treatments for incurable diseases such as Parkinson’s disease (PD). Here, we directly reprogrammed human fibroblasts into induced dopaminergic neuronal progenitors (hiDPs) and assess their applicability for regenerative PD therapy. We found that hiDPs maintain progenitor characteristics over 20 passages and showed unaltered differentiation potential to midbrain dopaminergic neurons. By next-generation sequencing, we confirm that even long-term cultured hiDPs retain genomic stability, resulting in absence of tumorigenicity when transplanted, indicating preclinical safety. The hiDPs differentiate into highly pure dopaminergic neurons expressing markers associated with positive graft outcomes without unwanted serotonergic neurons known to cause graft-induced dyskinesia. The therapeutic effect and safety were confirmed by transplantation in rodent PD models. Because our optimized reprogramming conditions generate highly expandable hiDPs enabling scaled production of clonal cells and overcoming quality control issues, we propose that our hiDPs can become a preferred autologous therapy for aged and feeble PD patients vulnerable to immunosuppression regimens.

2023-08-31 | GSE157392 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data