CD200-based cell sorting results in homogeneous transplantable striatal neuroblasts for human cell therapy for Huntington's disease

Neurodegenerative diseases are characterized by selective loss of neurons. Cell replacement therapies are the most promising therapeutic strategies to restore the neuronal functions lost during these neurodegenerative processes. However, cell replacement-based clinical trials for Huntington's (...

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Main Authors: Francisco J. Molina-Ruiz, Phil Sanders, Cinta Gomis, Jordi Abante, Francisco Londoño, Georgina Bombau, Mireia Galofré, Gal la Vinyes-Bassols, Veronica Monforte, Josep M. Canals
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Language:English
Published: Elsevier 2025-06-01
Series:Neurobiology of Disease
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Online Access:http://www.sciencedirect.com/science/article/pii/S0969996125001214
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author Francisco J. Molina-Ruiz
Phil Sanders
Cinta Gomis
Jordi Abante
Francisco Londoño
Georgina Bombau
Mireia Galofré
Gal la Vinyes-Bassols
Veronica Monforte
Josep M. Canals
author_facet Francisco J. Molina-Ruiz
Phil Sanders
Cinta Gomis
Jordi Abante
Francisco Londoño
Georgina Bombau
Mireia Galofré
Gal la Vinyes-Bassols
Veronica Monforte
Josep M. Canals
author_sort Francisco J. Molina-Ruiz
collection DOAJ
description Neurodegenerative diseases are characterized by selective loss of neurons. Cell replacement therapies are the most promising therapeutic strategies to restore the neuronal functions lost during these neurodegenerative processes. However, cell replacement-based clinical trials for Huntington's (HD) and Parkinson's diseases (PD) failed due to the large heterogeneity of the samples.Here, we identify CD200 as a cell surface marker for human striatal neuroblasts (NBs) using massively parallel single-cell RNA sequencing. Next, we set up a CD200-based immunomagnetic sorting pipeline that allows high-yield enrichment of human striatal NBs from in vitro differentiation of human pluripotent stem cells (hPSCs). We also show that sorted CD200-positive cells are striatal projection neuron (SPN)-committed NBs which survive upon intra-striatal transplantation in adult mice with no evidence of graft overgrowth in vivo.In conclusion, we implemented a new CD200 cell selection strategy that reduces the heterogeneity and batch-to-batch variation and potentially decreases the teratogenic risk of hPSC-based cell therapy for neurodegenerative diseases.
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spelling doaj-art-6d10bf5bfdb34f9f98014ac7032f3c902025-08-20T03:18:58ZengElsevierNeurobiology of Disease1095-953X2025-06-0120910690510.1016/j.nbd.2025.106905CD200-based cell sorting results in homogeneous transplantable striatal neuroblasts for human cell therapy for Huntington's diseaseFrancisco J. Molina-Ruiz0Phil Sanders1Cinta Gomis2Jordi Abante3Francisco Londoño4Georgina Bombau5Mireia Galofré6Gal la Vinyes-Bassols7Veronica Monforte8Josep M. Canals9Laboratory of Stem Cells and Regenerative Medicine, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences; Institute of Neurosciences; and Creatio, Production and Validation Center of Advanced Therapies, University of Barcelona, 08036 Barcelona, Spain; August Pi i Sunyer Biomedical Research Institute (IDIBAPS), 08036 Barcelona, SpainLaboratory of Stem Cells and Regenerative Medicine, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences; Institute of Neurosciences; and Creatio, Production and Validation Center of Advanced Therapies, University of Barcelona, 08036 Barcelona, Spain; August Pi i Sunyer Biomedical Research Institute (IDIBAPS), 08036 Barcelona, SpainLaboratory of Stem Cells and Regenerative Medicine, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences; Institute of Neurosciences; and Creatio, Production and Validation Center of Advanced Therapies, University of Barcelona, 08036 Barcelona, Spain; August Pi i Sunyer Biomedical Research Institute (IDIBAPS), 08036 Barcelona, SpainLaboratory of Stem Cells and Regenerative Medicine, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences; Institute of Neurosciences; and Creatio, Production and Validation Center of Advanced Therapies, University of Barcelona, 08036 Barcelona, Spain; August Pi i Sunyer Biomedical Research Institute (IDIBAPS), 08036 Barcelona, Spain; Department of Biomedical Data Science, Stanford University, Stanford, CA, United States of AmericaLaboratory of Stem Cells and Regenerative Medicine, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences; Institute of Neurosciences; and Creatio, Production and Validation Center of Advanced Therapies, University of Barcelona, 08036 Barcelona, Spain; August Pi i Sunyer Biomedical Research Institute (IDIBAPS), 08036 Barcelona, SpainLaboratory of Stem Cells and Regenerative Medicine, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences; Institute of Neurosciences; and Creatio, Production and Validation Center of Advanced Therapies, University of Barcelona, 08036 Barcelona, Spain; August Pi i Sunyer Biomedical Research Institute (IDIBAPS), 08036 Barcelona, SpainLaboratory of Stem Cells and Regenerative Medicine, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences; Institute of Neurosciences; and Creatio, Production and Validation Center of Advanced Therapies, University of Barcelona, 08036 Barcelona, Spain; August Pi i Sunyer Biomedical Research Institute (IDIBAPS), 08036 Barcelona, SpainLaboratory of Stem Cells and Regenerative Medicine, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences; Institute of Neurosciences; and Creatio, Production and Validation Center of Advanced Therapies, University of Barcelona, 08036 Barcelona, Spain; August Pi i Sunyer Biomedical Research Institute (IDIBAPS), 08036 Barcelona, SpainLaboratory of Stem Cells and Regenerative Medicine, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences; Institute of Neurosciences; and Creatio, Production and Validation Center of Advanced Therapies, University of Barcelona, 08036 Barcelona, Spain; August Pi i Sunyer Biomedical Research Institute (IDIBAPS), 08036 Barcelona, SpainLaboratory of Stem Cells and Regenerative Medicine, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences; Institute of Neurosciences; and Creatio, Production and Validation Center of Advanced Therapies, University of Barcelona, 08036 Barcelona, Spain; August Pi i Sunyer Biomedical Research Institute (IDIBAPS), 08036 Barcelona, Spain; Corresponding author at: Laboratory of Stem Cells and Regenerative Medicine, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences; Institute of Neurosciences; and Creatio, Production and Validation Center of Advanced Therapies, University of Barcelona, 08036 Barcelona, Spain.Neurodegenerative diseases are characterized by selective loss of neurons. Cell replacement therapies are the most promising therapeutic strategies to restore the neuronal functions lost during these neurodegenerative processes. However, cell replacement-based clinical trials for Huntington's (HD) and Parkinson's diseases (PD) failed due to the large heterogeneity of the samples.Here, we identify CD200 as a cell surface marker for human striatal neuroblasts (NBs) using massively parallel single-cell RNA sequencing. Next, we set up a CD200-based immunomagnetic sorting pipeline that allows high-yield enrichment of human striatal NBs from in vitro differentiation of human pluripotent stem cells (hPSCs). We also show that sorted CD200-positive cells are striatal projection neuron (SPN)-committed NBs which survive upon intra-striatal transplantation in adult mice with no evidence of graft overgrowth in vivo.In conclusion, we implemented a new CD200 cell selection strategy that reduces the heterogeneity and batch-to-batch variation and potentially decreases the teratogenic risk of hPSC-based cell therapy for neurodegenerative diseases.http://www.sciencedirect.com/science/article/pii/S0969996125001214Huntington's diseaseNeurodegenerative diseasesCell selectionCell replacement therapyRegenerative medicine
spellingShingle Francisco J. Molina-Ruiz
Phil Sanders
Cinta Gomis
Jordi Abante
Francisco Londoño
Georgina Bombau
Mireia Galofré
Gal la Vinyes-Bassols
Veronica Monforte
Josep M. Canals
CD200-based cell sorting results in homogeneous transplantable striatal neuroblasts for human cell therapy for Huntington's disease
Neurobiology of Disease
Huntington's disease
Neurodegenerative diseases
Cell selection
Cell replacement therapy
Regenerative medicine
title CD200-based cell sorting results in homogeneous transplantable striatal neuroblasts for human cell therapy for Huntington's disease
title_full CD200-based cell sorting results in homogeneous transplantable striatal neuroblasts for human cell therapy for Huntington's disease
title_fullStr CD200-based cell sorting results in homogeneous transplantable striatal neuroblasts for human cell therapy for Huntington's disease
title_full_unstemmed CD200-based cell sorting results in homogeneous transplantable striatal neuroblasts for human cell therapy for Huntington's disease
title_short CD200-based cell sorting results in homogeneous transplantable striatal neuroblasts for human cell therapy for Huntington's disease
title_sort cd200 based cell sorting results in homogeneous transplantable striatal neuroblasts for human cell therapy for huntington s disease
topic Huntington's disease
Neurodegenerative diseases
Cell selection
Cell replacement therapy
Regenerative medicine
url http://www.sciencedirect.com/science/article/pii/S0969996125001214
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