Dataset ID: 20
Dataset Details
Study Design
| Study Design Background |
Machado-Joseph disease (MJD) or spinocerebellar ataxia type 3, the most common dominant spinocerebellar ataxia (SCA) worldwide, is caused by over-repetition of a CAG repeat in the ATXN3 MJD1 gene, which translates into a polyglutamine tract within the ataxin-3 protein. There is no treatment for this fatal disorder. Despite evidence of the safety and efficacy of mesenchymal stromal cells (MSCs) in delaying SCA disease progression in exploratory clinical trials, unanticipated regression of patients to the status prior to treatment makes the investigation of causes and solutions urgent and imperative. In the present study, we compared the efficacy of a single intracranial injection with repeated systemic MSC administration in alleviating the MJD phenotype of two strongly severe genetic rodent models.
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|---|---|
| Study Description |
Repeated Mesenchymal Stromal Cell Treatment Sustainably Alleviates Machado-Joseph Disease
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| Study Type |
Preclinical
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| Study Subtype |
In vivo
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Publication
| Paper Linked |
Yes
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|---|---|
| Paper Title |
Repeated Mesenchymal Stromal Cell Treatment Sustainably Alleviates Machado-Joseph Disease
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| Paper Authors |
Catarina Oliveira Miranda, Adriana Marcelo, Teresa Pereira Silva, João Barata, Ana Vasconcelos-Ferreira, Dina Pereira, Clévio Nóbrega, Sónia Duarte, Inês Barros, Joana Alves, José Sereno, Lorena Itatí Petrella, João Castelhano, Vitor Hugo Paiva, Paulo Rodrigues-Santos, Vera Alves, Isabel Nunes-Correia, Rui Jorge Nobre, Célia Gomes, Miguel Castelo-Branco, Luís Pereira de Almeida
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| Affiliation |
"1.Center for Neuroscience and Cell Biology (CNC), University of Coimbra, Faculdade de Medicina, Rua Larga, Pólo I, 1° andar, 3004-504 Coimbra, Portugal 2. Institute for Interdisciplinary Research, University of Coimbra, Casa Costa Alemão – Pólo II, Rua Dom Francisco de Lemos, 3030-789 Coimbra, Portugal 3. Centre for Neuroscience and Cell Biology – Institute of Biomedical Imaging and Life Science (CNC.IBILI), University of Coimbra, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal 4. Doctoral Programme of Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal 5. Doctoral Programme in Experimental Biology and Biomedicine, CNC – University of Coimbra, Rua Larga, Faculdade de Medicina, Pólo I, 1° andar, 3004-504 Coimbra, Portugal 6. Coimbra Institute for Biomedical Imaging and Translational Research, Edifício do ICNAS, Polo 3, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal 7. Institute of Nuclear Science Applied to Health, University of Coimbra, Polo 3, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal 8. MARE - Marine and Environmental Sciences Centre, Department of Life Sciences, University of Coimbra, 3004-517 Coimbra, Portugal 9. Immunology Institute, Faculty of Medicine, University of Coimbra, Rua Larga, 3004-504 Coimbra, Portugal 10. Immunology and Oncology Laboratory, Center for Neurosciences and Cell Biology (CNC), University of Coimbra, Rua Larga, 3004-504, Portugal 11. Center of Investigation in Environment, Genetics and Oncobiology, Apartado 9015, 3001-301, Coimbra, Portugal 12. Coimbra Institute for Clinical and Biomedical Research, Faculty of Medicine, University of Coimbra, Polo 3, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal 13 Faculty of Pharmacy, University of Coimbra, Polo 3, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal"
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| Paper Journal |
Molecular Therapy
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| Paper Year |
2018
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| Paper DOI |
10.1016 j.ymthe.2018.07.007
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| Open Access |
Yes
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Study Component
| Multi Modality Images |
Yes
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|---|---|
| Imaging Modality |
MRI
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| Imaging Sub Modality |
T2w and MRS-1H
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| Radiation |
No
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| Imaging Coverage |
Brain
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Dataset Information
| Institution |
University of Coimbra
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|---|---|
| PI |
Luís Pereira de Almeida
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| Co PI |
Miguel Castelo-Branco
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| Country Of Institution |
Portugal
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| Imaging Facility |
Preclinical Imaging Unit
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| Euro Bio Imaging Node |
Brain Imaging Network
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| Country Of Imaging Facility |
Portugal
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| Funding |
Yes
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| Dataset Access |
Public
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| License |
 |
| Contact Person |
In Vivo Experimental Parameters
| Number Of Groups |
3
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|---|---|
| Types Of Groups |
WT, NT-MJD, MJD+MSC
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| Overall Sample Size |
15
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| Disease Model |
Neurological
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| Organ Or Tissue |
Brain
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| Sample Size For Each Group |
5
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| Randomization |
Yes
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| Blinding |
Yes
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| Statistical Methods |
Statistical analyses were performed in R statistical software (v3.0.1). Normality and homogeneity were assessed using Q-Q plots and Cleveland dot plots, respectively. Data were transformed if needed. Significance was set at p < 0.05.
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| Species |
Mice
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| Strain |
Tg-ATXN3-69Q MJD mice
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| Immune Status |
Immunecompetent
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| Sex |
Male and female
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| Age |
7 weeks
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| Weight |
20-24 grams
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| Genetic Manipulation |
Transgenic mouse model
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| Gene |
ATXN3 MJD1 gene
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Experimental Procedures
| Pharmacological Procedures Intervention And Control |
Yes
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|---|---|
| Pharmacological Drug |
Mesenchimal stem cells
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| Drug Dose |
4.5–8 × 107 MSCs kg
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| Volume |
70–150 μL
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| Site Or Route Of Administration |
Cerebellum
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| Frequency Of Administration |
Every 2–3 weeks four consecutive times
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| Blood Sampling |
No
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| Surgical Procedures Including Sham Surgery |
Yes
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| Target Organ Tissue |
Cerebellum
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| Pathogen Infection Intervention And Control |
No
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| Analgesic Plan To Relieve Pain Suffering And Distress |
Yes
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| Analgesic Name |
Buprenorphine
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| Route |
Intravenous
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| Anesthesia For Imaging |
Yes
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| Anesthesia Type |
Gas
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| Duration |
60 minutes
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| Anesthesia Drugs |
Isoflurane
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| Anesthesia Dose |
2% isoflurane
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| Monitoring Regime |
Respiratory and temperature raterespiratory and temperature rate
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| Euthanasia |
Yes
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| Method |
Anaesthesia overdose and cervical dislocation
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| Histology |
Yes
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| Tissues Collected Post Euthanasia |
Cerebellum
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| Timing Of Collection |
End of imaging
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| Imaging |
Yes
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| Frequency Of Imaging |
One time
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| Timing Of Imaging |
One time in the end of the treatment
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| Contrast Agent Or Radio Isotope Or Challenge With Gas Molecule |
No
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| Cell Lines |
Yes
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| Cell Line |
Mesenchymal stem cells
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| Provenance |
Isolated from the bone marrow of 6- to 8-week-old WT mice of both genders with a C57BL 6 background
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Image Acquisition
| Instrument Vendor |
BRUKER
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|---|---|
| Instrument Type |
Biospec 94 20 USR
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| Instrument Specifics |
9,4T
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| Image Acquisition Parameters |
T2_TuboRARE (TE TR=33.0 3800ms, 10 averages, 34 continuous slices with 0.5mm thickness and axial orientation); MRS cerebellum with PRESS_1H (TE TR=16.225 2500ms, 720 averages, voxel size 4.0*1.1*1.0)
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| Correction |
Room temperature coils (volume coil for excitation (86 112 mm of inner outer diameter, respectively) and a quadrature mouse surface coil for signal detection)
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| QA/QC |
Yes (Quality assurance of the resonators coils through QA-SNR sequence - BUKER method)
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Image Data
| Image Type |
DICOM
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|---|---|
| Image Scale |
DICOM
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| Format Compression |
DICOM
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| Dimensions |
2D
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| Overall Number Of Images |
57
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| Field Of View |
20 x 20
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| Dimension Extents |
256 x 256 x 34 slices
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| Size Description |
19.968*19.968*17mm
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| PI xel Voxel Size Description |
19.968*19.968*17mm
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| Quality Control |
No
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Analyzed Data
| Data Used For Analysis |
T2 (The cerebellum segmentation was carried out with custom made software developed in MATLAB programming language, describer in the paper). For MRS we use Lcmodel software.
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|---|---|
| Updated Year |
2025
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