In vivo survival and differentiation of Friedreich ataxia iPSC-derived sensory neurons transplanted in the adult dorsal root ganglia.
Serena ViventiStefano FrausinSara E HowdenShiang Y LimRocio K Finol-UrdanetaJeffrey R McArthurKwaku Dad Abu-BonsrahWayne NgJason IvanusicLachlan ThompsonMirella DottoriPublished in: Stem cells translational medicine (2021)
Friedreich ataxia (FRDA) is an autosomal recessive disease characterized by degeneration of dorsal root ganglia (DRG) sensory neurons, which is due to low levels of the mitochondrial protein Frataxin. To explore cell replacement therapies as a possible approach to treat FRDA, we examined transplantation of sensory neural progenitors derived from human embryonic stem cells (hESC) and FRDA induced pluripotent stem cells (iPSC) into adult rodent DRG regions. Our data showed survival and differentiation of hESC and FRDA iPSC-derived progenitors in the DRG 2 and 8 weeks post-transplantation, respectively. Donor cells expressed neuronal markers, including sensory and glial markers, demonstrating differentiation to these lineages. These results are novel and a highly significant first step in showing the possibility of using stem cells as a cell replacement therapy to treat DRG neurodegeneration in FRDA as well as other peripheral neuropathies.
Keyphrases
- induced pluripotent stem cells
- spinal cord
- cell therapy
- stem cells
- replacement therapy
- neuropathic pain
- embryonic stem cells
- single cell
- induced apoptosis
- early onset
- oxidative stress
- spinal cord injury
- endothelial cells
- cell cycle arrest
- smoking cessation
- intellectual disability
- brain injury
- mesenchymal stem cells
- machine learning
- binding protein
- signaling pathway
- blood brain barrier
- deep learning
- cell proliferation
- young adults
- childhood cancer
- artificial intelligence
- chemotherapy induced