دورية أكاديمية
Advancing Parkinson's disease treatment: cell replacement therapy with neurons derived from pluripotent stem cells.
| العنوان: | Advancing Parkinson's disease treatment: cell replacement therapy with neurons derived from pluripotent stem cells. |
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| المؤلفون: | Clark BJ; Department of Biomedical Engineering, UC Irvine, Irvine, CA 92697, United States., Lelos MJ; School of Biosciences, Museum Avenue, Cardiff University, Cardiff, CF10 3AX, United Kingdom., Loring JF; Department of Molecular Medicine, Scripps Research, La Jolla, CA 92030, United States. |
| المصدر: | Stem cells (Dayton, Ohio) [Stem Cells] 2024 Sep 10; Vol. 42 (9), pp. 781-790. |
| نوع المنشور: | Journal Article; Review |
| اللغة: | English |
| بيانات الدورية: | Publisher: Oxford University Press Country of Publication: England NLM ID: 9304532 Publication Model: Print Cited Medium: Internet ISSN: 1549-4918 (Electronic) Linking ISSN: 10665099 NLM ISO Abbreviation: Stem Cells Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2022- : Oxford : Oxford University Press Original Publication: Dayton, OH : AlphaMed Press, c1993- |
| مواضيع طبية MeSH: | Parkinson Disease*/therapy, Humans ; Pluripotent Stem Cells/cytology ; Pluripotent Stem Cells/transplantation ; Dopaminergic Neurons/transplantation ; Dopaminergic Neurons/metabolism ; Dopaminergic Neurons/cytology ; Cell- and Tissue-Based Therapy/methods ; Induced Pluripotent Stem Cells/cytology ; Induced Pluripotent Stem Cells/transplantation ; Stem Cell Transplantation/methods ; Animals ; Cell Differentiation |
| مستخلص: | The motor symptoms of Parkinson's disease (PD) are caused by the progressive loss of dopamine neurons from the substantia nigra. There are currently no treatments that can slow or reverse the neurodegeneration. To restore the lost neurons, international groups have initiated clinical trials using human embryonic or induced pluripotent stem cells (PSCs) to derive dopamine neuron precursors that are used as transplants to replace the lost neurons. Proof-of-principle experiments in the 1980s and 1990s showed that grafts of fetal ventral mesencephalon, which contains the precursors of the substantial nigra, could, under rare circumstances, reverse symptoms of the disease. Improvements in PSC technology and genomics have inspired researchers to design clinical trials using PSC-derived dopamine neuron precursors as cell replacement therapy for PD. We focus here on 4 such first-in-human clinical trials that have begun in the US, Europe, and Japan. We provide an overview of the sources of PSCs and the methods used to generate cells for transplantation. We discuss pros and cons of strategies for allogeneic, immune-matched, and autologous approaches and novel methods for overcoming rejection by the immune system. We consider challenges for safety and efficacy of the cells for durable engraftment, focusing on the genomics-based quality control methods to assure that the cells will not become cancerous. Finally, since clinical trials like these have never been undertaken before, we comment on the value of cooperation among rivals to contribute to advancements that will finally provide relief for the millions suffering from the symptoms of PD. (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.) |
| معلومات مُعتمدة: | F-1502 Parkinson's UK Senior Research Fellowship |
| فهرسة مساهمة: | Keywords: Parkinson’s disease; cell therapy; clinical trial; dopamine neurons; pluripotent stem cells |
| تواريخ الأحداث: | Date Created: 20240621 Date Completed: 20240910 Latest Revision: 20240910 |
| رمز التحديث: | 20240910 |
| DOI: | 10.1093/stmcls/sxae042 |
| PMID: | 38902932 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1549-4918 |
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| DOI: | 10.1093/stmcls/sxae042 |