2. Academic Validation
  3. Cryopreserved clinical-grade human embryonic stem cell-derived dopaminergic progenitors function in Parkinson's disease models

Cryopreserved clinical-grade human embryonic stem cell-derived dopaminergic progenitors function in Parkinson's disease models

  • Life Sci. 2023 Jul 29;329:121990. doi: 10.1016/j.lfs.2023.121990.
Somayeh Naderi 1,  Zahra Shiri 2,  Masoumeh Zarei-Kheirabadi 3,  Sepideh Mollamohammadi 3,  Parastoo Hosseini 3,  Golnoosh Rahimi 3,  Azadeh Moradmand 4,  Azam Samadian 4,  Amir Shojaei 5,  Meghdad Yeganeh 3,  Seyed Ahmad Mousavi 3,  Motahare Badri 3,  Adeleh Taei 4,  Seyedeh-Nafiseh Hassani 4,  Hossein Baharvand 6
Affiliations

Affiliations

  • 1 Department of Developmental Biology, School of Basic Sciences and Advanced Technologies in Biology, University of Science and Culture, Tehran, Iran; Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.
  • 2 Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran; Department of Brain and Cognitive Sciences, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.
  • 3 Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.
  • 4 Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran; Advanced Therapy Medicinal Product Technology Development Center (ATMP-TDC), Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.
  • 5 Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
  • 6 Department of Developmental Biology, School of Basic Sciences and Advanced Technologies in Biology, University of Science and Culture, Tehran, Iran; Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran. Electronic address: [email protected].
PMID: 37524159 DOI: 10.1016/j.lfs.2023.121990
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.

Keywords

Cell transplantation; Dopaminergic neurons; GMP; Human embryonic stem cells; Parkinson's disease.

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