Therapeutic function of iPSCs-derived primitive neuroepithelial cells in a rat model of Parkinson's disease

• Published in: Neurochemistry international Vol. 155; p. 105324
• Main Authors: Guo, Yu, Guan, Yuhan, Zhu, Huan, Sun, Tingting, Wang, Yuanyuan, Huang, Yuqi, Ma, Caiyun, Emery, Rik, Guan, Weijun, Wang, Chunjing, Liu, Changqing
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.05.2022
• Subjects: Animals; Cell Differentiation - physiology; Cell transplantation; Disease Models, Animal; Dopaminergic Neurons; Induced Pluripotent Stem Cells; Neuroepithelial cells; Neuroepithelial Cells - transplantation; Oxidopamine - toxicity; Parkinson Disease - therapy; Parkinson's disease; Rat induced pluripotent stem cells; Rats; Substantia Nigra; Rat induced pluripotent stem cells; Neuroepithelial cells; Parkinson's disease; Cell transplantation
• ISSN: 0197-0186; 1872-9754
• DOI: 10.1016/j.neuint.2022.105324

Induced pluripotent stem cells (iPSCs) are a promising unlimited source for cell replacement therapy of neurodegenerative disorders, including Parkinson's disease (PD). In the present study, rat iPSCs-derived primitive neuroepithelial cells (RiPSCs-iNECs) were successfully induced from rat iPSCs (RiPSCs) following two major developmental stages, and could generate neurospheres and differentiated into both neurons and astrocytes in vitro. Then, the RiPSCs-iNECs-GFP+ were unilaterally transplanted into the right substantia nigra (SN) of 6-hydroxydopamine-lesioned rat models of PD. The results demonstrated that the grafted RiPSCs-iNECs could survive in parkinsonian rat brain for at least 150 days, and many of them differentiated into tyrosine hydroxylase (TH)-positive cells. Furthermore, the PD model rats grafted with RiPSCs-iNECs exhibited a significant functional recovery from their parkinsonian behavioral defects. Histological studies showed that RiPSCs-iNECs could differentiate into multiple types of neurons including dopaminergic neurons, GFAP, Pax6, FoxA2 and DAT-positive cells, and induced dopaminergic neurons extended dense neurites into the host striatum. Thus, iPSCs derived primitive neuroepithelial cells could be an attractive candidate as a source of donor material for the treatment of PD, but the molecular mechanism needs further clarification. •RiPSCs could be induced into RiPSC-iNECs following two major stages in Vitro.•RiPSC-iNECs significantly improved the functional recovery of PD rat models.•Grafted RiPSCs-iNECs could survive in rat substantia nigra for at least 150 days.•Grafted RiPSCs-iNECs differentiated into neurons in the substantia nigra.