A5042827609- Pluripotent Stem Cells Research
- Parkinson's Disease Mechanisms and Treatments
- CRISPR and Genetic Engineering
- Neuroscience and Neuropharmacology Research
- Neuroscience and Neural Engineering
- Neurological disorders and treatments
- Neurogenesis and neuroplasticity mechanisms
- 3D Printing in Biomedical Research
- Nerve injury and regeneration
- RNA Interference and Gene Delivery
- RNA Research and Splicing
- Single-cell and spatial transcriptomics
- Alzheimer's disease research and treatments
- Neurotransmitter Receptor Influence on Behavior
- Nuclear Receptors and Signaling
- Glioma Diagnosis and Treatment
- Additive Manufacturing and 3D Printing Technologies
- Diet and metabolism studies
- Cell Image Analysis Techniques
- Autophagy in Disease and Therapy
- Spectroscopy Techniques in Biomedical and Chemical Research
- MicroRNA in disease regulation
- Memory and Neural Mechanisms
- Ion channel regulation and function
- Neurological diseases and metabolism
Lund University
2016-2025
Lund Science (Sweden)
2023
Wallenberg Wood Science Center
2018
Fondazione Santa Lucia
2013
Istituti di Ricovero e Cura a Carattere Scientifico
2013
Stem cell treatments for neurodegenerative diseases are expected to reach clinical trials soon. Most of the approaches currently under development involve transplantation immature progenitors that subsequently undergo phenotypic and functional maturation in vivo, predicting long-term graft outcome already at progenitor stage remains a challenge. Here, we took an unbiased approach identify predictive markers expressed dopamine neuron correlate with animal model Parkinson's disease through...
The possibility of directly converting non-neuronal cells into neurons in situ the brain would open therapeutic avenues aimed at repairing after injury or degenerative disease. We have developed an adeno-associated virus (AAV)-based reporter system that allows selective GFP labeling reprogrammed neurons. In this system, is turned on only where it stable and maintained for long time periods, allowing histological functional characterization mature When combined with a modified rabies...
Abstract Objective: Striatal serotonin projections have been implicated in levodopa‐induced dyskinesia by providing an unregulated source of dopamine release. We set out to determine whether these are affected levodopa treatment a way that would favor the occurrence dyskinesia. Methods: As index terminal innervation density, we measured radioligand binding plasma membrane transporter (SERT) levodopa‐treated dyskinetic and nondyskinetic subjects, using brain tissue from both rat monkey models...
l-DOPA-induced dyskinesia (LID) in Parkinson9s disease has been linked to altered dopamine and glutamate transmission within the basal ganglia. In present study, we compared compounds targeting specific subtypes of receptors or calcium channels for their ability attenuate LID associated activation striatal nuclear signaling gene expression rat. Rats with 6-hydroxydopamine lesions were treated acutely chronically l-DOPA combination following selective compounds: antagonists group I...
Glial progenitor cells are widely distributed in brain parenchyma and represent a suitable target for future therapeutic interventions that generate new neurons via situ reprogramming. Previous studies have shown successful reprogramming of mouse glia into whereas the conversion human glial remains challenging due to limited accessibility tissue. Here, we used recently developed stem cell-based model (hGPCs) direct neural by overexpressing set transcription factors involved GABAergic...
Converting resident glia into functional and subtype-specific neurons in vivo by delivering reprogramming genes directly to the brain provides a step forward toward possibility of treating injuries or diseases. To date, it has been possible obtain GABAergic glutamatergic via conversion, but precise phenotype these cells not yet analyzed detail. Here, we show that reprogrammed using Ascl1, Lmx1a, Nurr1 functionally mature integrate existing circuitry majority have properties fast-spiking,...
Abstract Direct conversion of human fibroblasts into mature and functional neurons, termed induced neurons ( iN s), was achieved for the first time 6 years ago. This technology offers a promising shortcut obtaining patient‐ disease‐specific disease modeling, drug screening, other biomedical applications. However, from adult donors do not reprogram as easily fetal donors, no current reprogramming approach is sufficiently efficient to allow use this using patient‐derived material large‐scale...
Abstract Three-dimensional brain organoids have emerged as a valuable model system for studies of human development and pathology. Here we establish midbrain organoid culture to study the developmental trajectory from pluripotent stem cells mature dopamine neurons. Using single cell RNA sequencing, identify presence three molecularly distinct subtypes neurons with high similarity those in developing adult midbrain. However, despite significant advancements field, use can be limited by issues...
Human in vitro models of neural tissue with tunable microenvironment and defined spatial arrangement are needed to facilitate studies brain development disease. Towards this end, embedded printing inside granular gels holds great promise as it allows precise patterning extremely soft constructs. However, support formulations restricted only a handful materials. Therefore, there has been need for novel materials that take advantage versatile biomimicry bulk hydrogels while providing...
Many neurodegenerative diseases are characterized by the presence of intracellular protein aggregates, resulting in alterations autophagy. However, consequences impaired autophagy for neuronal function remain poorly understood. In this study, we used cell culture and mouse models huntingtin aggregation as well post-mortem material from patients with Huntington's disease to demonstrate that Argonaute-2 (AGO2) accumulates aggregates is due Accumulation AGO2, a key factor RNA-induced silencing...
We have developed an efficient approach to generate functional induced dopaminergic (DA) neurons from adult human dermal fibroblasts. When performing DA neuronal conversion of patient fibroblasts with idiopathic Parkinson's disease (PD), we could specifically detect disease-relevant pathology in these cells. show that the patient-derived maintain age-related properties donor and exhibit lower basal chaperone-mediated autophagy compared healthy donors. Furthermore, stress-induced resulted...
Induced neurons (iNs) offer a novel source of human that can be explored for applications disease modelling, diagnostics, drug screening and cell replacement therapy. Here we present protocol highly efficient generation functional iNs from fetal fibroblasts also demonstrate the ability these converted (hiNs) to survive transplantation maintain their phenotype in adult rat brain. The encompasses delay transgene activation after viral transduction resulted significant increase conversion...
Reprogramming of cellular identity using exogenous expression transcription factors (TFs) is a powerful and exciting tool for tissue engineering, disease modeling, regenerative medicine. However, generation desired cell types this approach often plagued by inefficiency, slow conversion, an inability to produce mature functional cells. Here, we show that constitutively active SMAD2/3 significantly improves the efficiency induced pluripotent stem (iPSC) Yamanaka factors. Mechanistically, SMAD3...
Significant efforts are ongoing to develop refined differentiation protocols generate midbrain dopamine (DA) neurons from pluripotent stem cells for application in disease modeling, diagnostics, drug screening and cell-based therapies Parkinson's disease. An increased understanding of the timing molecular mechanisms that promote generation distinct subtypes human DA during development will be essential guiding future molecularly defined subtype-specific cells. Here, we use droplet-based...
ABSTRACT Intracerebral transplantation of stem cell-derived oligodendrocytes (OLs) holds promise as a new strategy for repairing demyelinated brain tissue. However, two challenges hinder clinical translation: the slow and inefficient generation human OLs using protocols described to date, limited insight into their remyelination potential, which has only been evaluated in vitro or xenotransplantation studies, failing capture critical human-specific cellular interactions involved myelination....
Recent findings show that human fibroblasts can be directly programmed into functional neurons without passing via a proliferative stem cell intermediate. These open up the possibility of generating subtype-specific origin for therapeutic use from fetal cell, patients themselves, or matched donors. In this study, we present an improved system direct neural conversion fibroblasts. The reprogramming genes are regulated by neuron-specific microRNA, miR-124, such each turns off expression once...
The transcription factor ΔFosB is a mediator of maladaptive neuroplasticity in animal models Parkinson's disease (PD) and L-DOPA-induced dyskinesia. Using an antibody that recognizes all known isoforms FosB ΔFosB, we have examined the expre
Human pluripotent stem cells (hPSCs) are intrinsically able to self-organize into cerebral organoids that mimic features of developing human brain tissue. These three-dimensional structures provide a unique opportunity generate cytoarchitecture and cell-cell interactions reminiscent complexity in dish. However, current vitro organoid methodologies often result intra-organoid variability, limiting their use recapitulating later developmental stages as well disease modeling drug discovery. In...
Human glial progenitor cells (hGPCs) are promising cellular substrates to explore for the in situ production of new neurons brain repair. Proof concept direct neuronal reprogramming progenitors has been obtained mouse models vivo, but conversion using human not yet demonstrated. Such studies have difficult perform since hGPCs born late during fetal development, with limited accessibility vitro culture. In this study, we show proof hGPC and also establish a renewable reproducible stem...