In vivo survival and differentiation of Friedreich ataxia iPSC-derived sensory neurons transplanted in the adult dorsal root ganglia

Serena Viventi; Stefano Frausin; Sara E Howden; Shiang Y Lim; Rocio K Finol-Urdaneta; Jeffrey R McArthur; Kwaku Dad Abu-Bonsrah; Wayne Ng; Jason Ivanusic; Lachlan Thompson; Mirella Dottori

doi:10.1002/sctm.20-0334

In vivo survival and differentiation of Friedreich ataxia iPSC-derived sensory neurons transplanted in the adult dorsal root ganglia

Stem Cells Transl Med. 2021 Aug;10(8):1157-1169. doi: 10.1002/sctm.20-0334. Epub 2021 Mar 18.

Authors

Serena Viventi^{1

2}, Stefano Frausin², Sara E Howden³, Shiang Y Lim^{4

5}, Rocio K Finol-Urdaneta⁶, Jeffrey R McArthur⁶, Kwaku Dad Abu-Bonsrah^{3

7}, Wayne Ng^{8

9}, Jason Ivanusic¹⁰, Lachlan Thompson², Mirella Dottori^{1

6

10}

Affiliations

¹ Department of Biomedical Engineering, The University of Melbourne, Parkville, Australia.
² The Florey Institute of Neuroscience and Mental Health, Parkville, Australia.
³ The Murdoch Children's Research Institute, Royal Children's Hospital, Parkville, Australia.
⁴ O'Brien Institute Department, St Vincent's Institute of Medical Research, Fitzroy, Australia.
⁵ Department of Surgery, The University of Melbourne, St Vincent Hospital, Fitzroy, Australia.
⁶ Illawarra Health and Medical Research Institute, University of Wollongong, Keiraville, Australia.
⁷ Department of Paediatrics, The University of Melbourne, Parkville, Australia.
⁸ School of Medicine, Griffith University, Gold Coast, Australia.
⁹ Department of Neurosurgery, Gold Coast University Hospital, Southport, Australia.
¹⁰ Department of Anatomy and Neuroscience, The University of Melbourne, Parkville, Australia.

Abstract

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.

Keywords: dorsal root ganglia; human pluripotent stem cells; sensory neurons; transplantation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Friedreich Ataxia* / metabolism
Friedreich Ataxia* / therapy
Ganglia, Spinal
Humans
Induced Pluripotent Stem Cells* / metabolism
Peripheral Nervous System Diseases*
Sensory Receptor Cells