Dopaminergic Progenitors Derived From Epiblast Stem Cells Function Similarly to Primary VM-Derived Progenitors When Transplanted Into a Parkinson’s Disease Model

Frontiers in Neuroscience

Andreas Heuer¹  Sophie V. Precious²  Stephen B. Dunnett²  Anne E. Rosser³  Claire M. Kelly⁴  Gaynor A. Smith⁵  Emma L. Lane⁶  Ines Jaeger⁷  Meng Li⁷ 

[1] Behavioural Neuroscience Laboratory, Department of Experimental Medical Sciences, Lund University, Lund, Sweden;Brain Repair Group, School of Biosciences, Cardiff University, Cardiff, United Kingdom;MRC Centre for Neuropsychiatric Genetics and Genomics, School of Medicine, Cardiff University, Cardiff, United Kingdom;School of Health Sciences, Cardiff Metropolitan University, Cardiff, United Kingdom;School of Medicine, UK Dementia Research Institute, Cardiff University, Cardiff, United Kingdom;School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Cardiff, United Kingdom;Stem Cell Neurogenesis Group, School of Medicine and Biosciences, Neuroscience and Mental Health Research Institute, Cardiff University, Cardiff, United Kingdom;Wales Brain Repair and Intracranial Neurotherapeutics Unit, School of Medicine, Cardiff University, Cardiff, United Kingdom;

关键词: transplantation;    Parkinson’s disease;    dopaminergic neurons;    primary fetal ventral mesencephalon;    stem cells;   

DOI  :  10.3389/fnins.2020.00312

来源: DOAJ

【 摘 要 】

Neural transplantation in neurodegenerative diseases such as Parkinson’s disease (PD) offers to replace cells lost during the progression of the disease process. Primary fetal ventral mesencephalon (VM), the origin of bona fide midbrain dopaminergic (DAergic) precursors, is currently the gold standard source of cells for transplantation in PD. However, the use of tissue from this source raises ethical and logistical constraints necessitating the need for alternative supplies of donor cells. The requirement of any alternative donor cell source is to have the capability to generate authentic mature DAergic neurons, which could be utilized in cell-replacement strategies. Mouse pluripotent stem cells can efficiently generate electrochemically mature midbrain DAergic precursors in vitro using a stepwise control of FGF signaling. Here, we have compared DAergic transplants derived from two progenitor cell sources in an allograft system: mouse epiblast stem cells (EpiSC) and primary fetal mouse VM tissue. Cells were transplanted into the striatum of 6-OHDA lesioned mice pre-treated with L-DOPA. Drug-induced rotations, a number of motor tests and drug-induced abnormal involuntary movements (AIMs) were assessed. Functional improvements were demonstrated post-transplantation in some behavioral tests, with no difference in graft volume or the number of TH immuno-positive cells in the grafts of the two transplant groups. L-DOPA-induced AIMs and amphetamine-induced AIMs were observed in both transplant groups, with no differences in rate or severity between the two groups. Collectively, in this mouse-to-mouse allograft system, we report no significant differences in the functional ability between the gold standard primary VM derived and pluripotent stem cell-derived DAergic transplants.

【 授权许可】

Unknown