In Vivo Survival and Differentiation of Friedreich Ataxia iPSC-Derived Sensory Neurons Transplanted in the Adult Dorsal Root Ganglia-Reference-Cited by-同舟云学术

In Vivo Survival and Differentiation of Friedreich Ataxia iPSC-Derived Sensory Neurons Transplanted in the Adult Dorsal Root Ganglia

Published:2021-03-18 Issue:8 Volume:10 Page:1157-1169
ISSN:2157-6564
Container-title:Stem Cells Translational Medicine
language:en
Short-container-title:

Author:

Viventi Serena¹²,Frausin Stefano²,Howden Sara E.³,Lim Shiang Y.⁴⁵,Finol-Urdaneta Rocio K.⁶,McArthur Jeffrey R.⁶,Abu-Bonsrah Kwaku Dad³⁷,Ng Wayne⁸⁹,Ivanusic Jason¹⁰,Thompson Lachlan²,Dottori Mirella¹⁶¹⁰^ORCID

Affiliation:

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

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.

Funder

Melbourne International Fee Remission Scholarship

Melbourne International Research Scholarship

Australian Research Council Future Fellowship

University of Wollongong

Illawarra Health and Medical Research Institute

The University of Melbourne

Friedreich's Ataxia Research Association Australasia

Friedreich's Ataxia Research Alliance USA

Publisher

Oxford University Press (OUP)

Subject