Abstract

In regenerative medicine applications, the differentiation stage of implanted stem cells must be optimized to control cell fate and enhance therapeutic efficacy. We investigated the therapeutic potential of human induced pluripotent stem cell (iPSC)-derived cells at two differentiation stages on peripheral nerve regeneration. Neural crest stem cells (NCSCs) and Schwann cells (NCSC-SCs) derived from iPSCs were used to construct a tissue-engineered nerve conduit that was applied to bridge injured nerves in a rat sciatic nerve transection model. Upon nerve conduit implantation, the NCSC group showed significantly higher electrophysiological recovery at 1 month as well as better gastrocnemius muscle recovery at 5 months than the acellular group, but the NCSC-SC group didn’t. Both transplanted NCSCs and NCSC-SCs interacted with newly-growing host axons, while NCSCs showed better survival rate and distribution. The transplanted NCSCs mainly differentiated into Schwann cells with no teratoma formation, and they secreted higher concentrations of brain-derived neurotrophic factor and nerve growth factor than NCSC-SCs. In conclusion, transplantation of iPSC-NCSCs accelerated functional nerve recovery with the involvement of stem cell differentiation and paracrine signaling. This study unravels the in vivo performance of stem cells during tissue regeneration, and provides a rationale of using appropriate stem cells for regenerative medicine.

Details

Title
The Differentiation Stage of Transplanted Stem Cells Modulates Nerve Regeneration
Author
Ching-Wen, Huang 1 ; Wen-Chin, Huang 2 ; Qiu, Xuefeng 3 ; Flavia Fernandes Ferreira da Silva 4 ; Wang, Aijun 5   VIAFID ORCID Logo  ; Patel, Shyam 1 ; Nesti, Leon J 6 ; Mu-Ming Poo 7 ; Li, Song 8 

1  Department of Bioengineering, University of California, Berkeley, California, USA 
2  Department of Bioengineering, University of California, Berkeley, California, USA; UC Berkeley-UCSF Graduate Program in Bioengineering, Berkeley, California, USA 
3  Department of Bioengineering, University of California, Berkeley, California, USA; Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China 
4  Instituto de Macromoléculas Professora Eloisa Mano, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil 
5  Department of Surgery, University of California, Davis, School of Medicine, Sacramento, California, USA 
6  Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA; Clinical and Experimental Orthopaedics, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA; Department of Orthopaedic Surgery, Walter Reed National Military Medical Center, Bethesda, Maryland, USA 
7  Department of Molecular and Cell Biology, University of California, Berkeley, California, USA 
8  Department of Bioengineering, University of California, Berkeley, California, USA; Department of Bioengineering, University of California, Los Angeles, California, USA; Department of Medicine, University of California, Los Angeles, California, USA 
Pages
1-12
Publication year
2017
Publication date
Dec 2017
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41598-017-17043-4
ProQuest document ID
1983425057
Copyright
© 2017. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.