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Newly Generated 3D Schwann-Like Cell Spheroids From Human Adipose-Derived Stem Cells Using a Modified Protocol
Peripheral nerve injury (PNI) is a relatively frequent type of trauma that results in the suffering of many patients worldwide every year. Schwann cells (SCs) are expected to be applied in cell therapy because of their ability to promote peripheral nerve regeneration. However, the lack of clinically...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
SAGE Publications
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9087224/ https://www.ncbi.nlm.nih.gov/pubmed/35469470 http://dx.doi.org/10.1177/09636897221093312 |
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author | Chen, Shuhai Ikemoto, Tetsuya Tokunaga, Takuya Okikawa, Shouhei Miyazaki, Katsuki Yamada, Shinichiro Saito, Yu Morine, Yuji Shimada, Mitsuo |
author_facet | Chen, Shuhai Ikemoto, Tetsuya Tokunaga, Takuya Okikawa, Shouhei Miyazaki, Katsuki Yamada, Shinichiro Saito, Yu Morine, Yuji Shimada, Mitsuo |
author_sort | Chen, Shuhai |
collection | PubMed |
description | Peripheral nerve injury (PNI) is a relatively frequent type of trauma that results in the suffering of many patients worldwide every year. Schwann cells (SCs) are expected to be applied in cell therapy because of their ability to promote peripheral nerve regeneration. However, the lack of clinically renewable sources of SCs hinders the application of SC-based therapies. Adipose-derived stem cells (ADSCs) have generated great interest in recent years because of their multipotency and ease of harvest, and they have already been verified to differentiate into Schwann-like cells (SLCs) in vitro. However, the efficiency of differentiation and the functions of SLCs remain unsatisfactory. We newly generated three-dimensional (3D) SLC spheroids from ADSCs using a modified protocol with human recombinant peptide (RCP) petaloid μ-piece. Morphological analysis, gene expression analysis by qRT-PCR, ELISA measurement of the secretion capabilities of neurotrophic factors, and neurite formation assay were performed to evaluate the functions of these 3D SLCs in vitro. Motor function recovery was measured in a sciatic nerve injury mouse model to analyze the nerve regeneration-promoting effect of 3D SLCs in vivo. The differentiation efficiency and the secretion of neurotrophic factors were enhanced in 3D SLCs compared with conventional SLCs. 3D SLCs could more effectively promote neurite growth and longer neurite extension in a neuron-like SH-SY5Y model. Additionally, 3D SLCs had a better therapeutic effect on nerve regeneration after transplantation into the sciatic nerve injury mouse model. These findings demonstrated that the potential of ADSC-derived SLCs to promote nerve regeneration could be significantly increased using our modified differentiation protocol and by assembling cells into a 3D sphere conformation. Therefore, these cells have great potential and can be used in the clinical treatment of PNI. |
format | Online Article Text |
id | pubmed-9087224 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | SAGE Publications |
record_format | MEDLINE/PubMed |
spelling | pubmed-90872242022-05-11 Newly Generated 3D Schwann-Like Cell Spheroids From Human Adipose-Derived Stem Cells Using a Modified Protocol Chen, Shuhai Ikemoto, Tetsuya Tokunaga, Takuya Okikawa, Shouhei Miyazaki, Katsuki Yamada, Shinichiro Saito, Yu Morine, Yuji Shimada, Mitsuo Cell Transplant Original Article Peripheral nerve injury (PNI) is a relatively frequent type of trauma that results in the suffering of many patients worldwide every year. Schwann cells (SCs) are expected to be applied in cell therapy because of their ability to promote peripheral nerve regeneration. However, the lack of clinically renewable sources of SCs hinders the application of SC-based therapies. Adipose-derived stem cells (ADSCs) have generated great interest in recent years because of their multipotency and ease of harvest, and they have already been verified to differentiate into Schwann-like cells (SLCs) in vitro. However, the efficiency of differentiation and the functions of SLCs remain unsatisfactory. We newly generated three-dimensional (3D) SLC spheroids from ADSCs using a modified protocol with human recombinant peptide (RCP) petaloid μ-piece. Morphological analysis, gene expression analysis by qRT-PCR, ELISA measurement of the secretion capabilities of neurotrophic factors, and neurite formation assay were performed to evaluate the functions of these 3D SLCs in vitro. Motor function recovery was measured in a sciatic nerve injury mouse model to analyze the nerve regeneration-promoting effect of 3D SLCs in vivo. The differentiation efficiency and the secretion of neurotrophic factors were enhanced in 3D SLCs compared with conventional SLCs. 3D SLCs could more effectively promote neurite growth and longer neurite extension in a neuron-like SH-SY5Y model. Additionally, 3D SLCs had a better therapeutic effect on nerve regeneration after transplantation into the sciatic nerve injury mouse model. These findings demonstrated that the potential of ADSC-derived SLCs to promote nerve regeneration could be significantly increased using our modified differentiation protocol and by assembling cells into a 3D sphere conformation. Therefore, these cells have great potential and can be used in the clinical treatment of PNI. SAGE Publications 2022-04-25 /pmc/articles/PMC9087224/ /pubmed/35469470 http://dx.doi.org/10.1177/09636897221093312 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by-nc/4.0/This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage). |
spellingShingle | Original Article Chen, Shuhai Ikemoto, Tetsuya Tokunaga, Takuya Okikawa, Shouhei Miyazaki, Katsuki Yamada, Shinichiro Saito, Yu Morine, Yuji Shimada, Mitsuo Newly Generated 3D Schwann-Like Cell Spheroids From Human Adipose-Derived Stem Cells Using a Modified Protocol |
title | Newly Generated 3D Schwann-Like Cell Spheroids From Human
Adipose-Derived Stem Cells Using a Modified Protocol |
title_full | Newly Generated 3D Schwann-Like Cell Spheroids From Human
Adipose-Derived Stem Cells Using a Modified Protocol |
title_fullStr | Newly Generated 3D Schwann-Like Cell Spheroids From Human
Adipose-Derived Stem Cells Using a Modified Protocol |
title_full_unstemmed | Newly Generated 3D Schwann-Like Cell Spheroids From Human
Adipose-Derived Stem Cells Using a Modified Protocol |
title_short | Newly Generated 3D Schwann-Like Cell Spheroids From Human
Adipose-Derived Stem Cells Using a Modified Protocol |
title_sort | newly generated 3d schwann-like cell spheroids from human
adipose-derived stem cells using a modified protocol |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9087224/ https://www.ncbi.nlm.nih.gov/pubmed/35469470 http://dx.doi.org/10.1177/09636897221093312 |
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