ArticleProceedings of the National Academy of Sciences of the United States of America2015
Transcriptome analysis reveals transmembrane targets on transplantable midbrain dopamine progenitors.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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37 citing papers in PubMed, 57 citations in OpenAlex.
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- iPS cell-based therapy for Parkinson's disease: A Kyoto trial.Regenerative therapy · 2020Article
- Preclinical evaluation of patient-derived cells shows promise for Parkinson's disease.The Journal of clinical investigation · 2020Article
- Midbrain Dopaminergic Neuron Development at the Single Cell Level:Frontiers in cell and developmental biology · 2020Review
- Pluripotent Stem Cell Therapies for Parkinson Disease: Present Challenges and Future Opportunities.Frontiers in cell and developmental biology · 2020Review
- Induced pluripotent stem cell-derived vascular smooth muscle cells.Vascular biology (Bristol, England) · 2020Review
- Modeling Parkinson's Disease Using Induced Pluripotent Stem Cells.Stem cells international · 2020Review
- Isolation of LMX1a Ventral Midbrain Progenitors Improves the Safety and Predictability of Human Pluripotent Stem Cell-Derived Neural Transplants in Parkinsonian Disease.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Article
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5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
An important challenge for the continued development of cell therapy for Parkinson's disease (PD) is the establishment of procedures that better standardize cell preparations for use in transplantation. Although cell sorting has been an anticipated strategy, its application has been limited by lack of knowledge regarding transmembrane proteins that can be used to target and isolate progenitors for midbrain dopamine (mDA) neurons. We used a "FACS-array" approach to identify 18 genes for transmembrane proteins with high expression in mDA progenitors and describe the utility of four of these targets (Alcam, Chl1, Gfra1, and Igsf8) for isolating mDA progenitors from rat primary ventral mesencephalon through flow cytometry. Alcam and Chl1 facilitated a significant enrichment of mDA neurons following transplantation, while targeting of Gfra1 allowed for robust separation of dopamine and serotonin neurons. Importantly, we also show that mDA progenitors isolated on the basis of transmembrane proteins are capable of extensive, functional innervation of the host striatum and correction of motor impairment in a unilateral model of PD. These results are highly relevant for current efforts to establish safe and effective stem cell-based procedures for PD, where clinical translation will almost certainly require safety and standardization measures in order to deliver well-characterized cell preparations.
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