Artikel
Investigation of nerve regeneration promoting factor in bioabsorbable nerve conduits coated with induced pluripotent stem cell-derived neurospheres
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Autoren
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Takuya Yokoi
- The Department of Orthopaedic Surgery, Osaka City University, Graduate School of Medicine, Osaka, Japan
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Takuya Uemura
- The Department of Orthopaedic Surgery, Osaka General Hospital of West Japan Railway Company, Osaka, Japan
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Kiyohito Takamatsu
- The Department of Orthopaedic Surgery, Yodogawa Christian Hospital, Osaka, Japan
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Kosuke Shintani
- The Department of Orthopaedic Surgery, Osaka City University, Graduate School of Medicine, Osaka, Japan
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Ema Onode
- The Department of Orthopaedic Surgery, Osaka City University, Graduate School of Medicine, Osaka, Japan
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Mitsuhiro Okada
- The Department of Orthopaedic Surgery, Osaka City University, Graduate School of Medicine, Osaka, Japan
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Hiroaki Nakamura
- The Department of Orthopaedic Surgery, Osaka City University, Graduate School of Medicine, Osaka, Japan
| Veröffentlicht: | 6. Februar 2020 |
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Gliederung
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Introduction: We previously reported the effectiveness of a bioabsorbable nerve conduit coated with iPSc-derived neurospheres in young and aged mice. Transplanted neurospheres in the nerve conduit differentiated into S100 positive - Schwann-like cells and migrated adjacent to nerve stumps. These cells maintained thier propertiy and remained, and located in the vicinity of the axons at least 14 days after transplantation. Here, we ivestigated nerve regeneration promoting factor in bioabsorbable nerve conduits coated with neurospheres.
Methods: The nerve conduit (external diameter 2 mm, internal diameter 1 mm and length 7 mm) was composed of an outer layer of a poly lactide mesh and an inner layer of a porous sponge composed of 50% L-lactide and 50% caprolactone. Mouse iPS cells were neurally induced in vitro using a published protocol. The secondary neurospheres derived from mouse iPS cells were suspended in each conduit (2,600,000-4,000,000 cells per conduit) and cultured in the conduit for 14 days. We then implanted them in the left sciatic nerve gap (5 mm) as iPSc groups (young mouse; n=6, aged mouse; n=6). Bridging of the nerve gap using the nerve conduit alone was designated as the control groups (young mouse group; n=5, aged mouse group; n=5). We investgaed gene expression of nerve regeneration factor in the nerve conduit by using real time PCR on Day 4 and Day 7 after transplantation and compared iPS group with control group.
Results and Conclusions: In the iPSc groups, on Day 4 and Day 7 after transplantation, gene expression of nerve regeneration promoting factors (ATF3, BDNF, and GDNF) was elevated compared with control groups.
According to in vivo imaging results in the same experimental system, the survival rate of transplanted neurospheres in the nerve cousuit increases at the early phase (Day 4 and Day 7) after transplantation. From the results of this study, it is considered that the these neurotrophic factors and transcription factor increased in the nerve conduit at the early phase, which may promoted peripheral nerve regeneration.
