1. Cryopreserved clinical-grade human embryonic stem cell-derived dopaminergic progenitors function in Parkinson's disease models.
- Author
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Naderi S, Shiri Z, Zarei-Kheirabadi M, Mollamohammadi S, Hosseini P, Rahimi G, Moradmand A, Samadian A, Shojaei A, Yeganeh M, Mousavi SA, Badri M, Taei A, Hassani SN, and Baharvand H
- Subjects
- Humans, Rats, Animals, Dopaminergic Neurons physiology, Cell Differentiation, Dopamine metabolism, Mesencephalon metabolism, Parkinson Disease therapy, Parkinson Disease metabolism, Human Embryonic Stem Cells, Pluripotent Stem Cells
- Abstract
Aim: Parkinson's Disease (PD) is a common age-related neurodegenerative disorder with a rising prevalence. Human pluripotent stem cells have emerged as the most promising source of cells for midbrain dopaminergic (mDA) neuron replacement in PD. This study aimed to generate transplantable mDA progenitors for treatment of PD., Materials and Methods: Here, we optimized and fine-tuned a differentiation protocol using a combination of small molecules and growth factors to induce mDA progenitors to comply with good manufacturing practice (GMP) guidelines based on our clinical-grade human embryonic stem cell (hESC) line., Key Findings: The resulting mDA progenitors demonstrated robust differentiation and functional properties in vitro. Moreover, cryopreserved mDA progenitors were transplanted into 6-hydroxydopamine-lesioned rats, leading to functional recovery., Significance: We demonstrate that our optimized protocol using a clinical hESC line is suitable for generating clinical-grade mDA progenitors and provides the ground work for future translational applications., Competing Interests: Declaration of competing interest No competing financial interests exist., (Copyright © 2023 Elsevier Inc. All rights reserved.)
- Published
- 2023
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