Long-Term Efficacy and Safety Outcomes of Transplantation of Induced Pluripotent Stem Cell-Derived Neurospheres with Bioabsorbable Nerve Conduits for Peripheral Nerve Regeneration in Mice

2015 ◽  
Vol 200 (1) ◽  
pp. 78-91 ◽  
Author(s):  
Takuya Uemura ◽  
Mikinori Ikeda ◽  
Kiyohito Takamatsu ◽  
Takuya Yokoi ◽  
Mitsuhiro Okada ◽  
...  
2021 ◽  
pp. 1-11
Author(s):  
Takuya Yokoi ◽  
Takuya Uemura ◽  
Kiyohito Takamatsu ◽  
Kosuke Shintani ◽  
Ema Onode ◽  
...  

BACKGROUND: We previously demonstrated that a bioabsorbable nerve conduit coated with mouse induced pluripotent stem cell (iPSC)-derived neurospheres accelerated peripheral nerve regeneration in mice. OBJECTIVE: We examined the fate and utility of iPSC-derived neurospheres transplanted with nerve conduits for the treatment of sciatic nerve gaps in mice. METHODS: Complete 5 mm defects were created in sciatic nerves and reconstructed using nerve conduits that were either uncoated or coated with mouse iPSC-derived neurospheres. The survival of the neurospheres on the nerve conduits was tracked using an in vivo imaging. The localization of the transplanted cells and regenerating axons was examined histologically. The gene expression levels in the nerve conduits were evaluated. RESULTS: The neurospheres survived for at least 14 days, peaking at 4–7 days after implantation. The grafted neurospheres remained as Schwann-like cells within the nerve conduits and migrated into the regenerated axons. The expression levels of ATF3, BDNF, and GDNF in the nerve conduit coated with neurospheres were upregulated. CONCLUSIONS: Mouse iPSC-derived neurospheres transplanted with nerve conduits for the treatment of sciatic nerve defects in mice migrated into regenerating axons, survived as Schwann-like cells, and promoted axonal growth with an elevation in the expression of nerve regeneration-associated trophic factors.


Author(s):  
Jee Myung Yang ◽  
Sunho Chung ◽  
KyungA Yun ◽  
Bora Kim ◽  
Seongjun So ◽  
...  

AbstractRetinal degenerative disorders, including age-related macular degeneration and retinitis pigmentosa (RP), are characterized by the irreversible loss of photoreceptor cells and retinal pigment epithelial (RPE) cells; however, the long-term effect of implanting both human induced pluripotent stem cell (hiPSC)-derived RPE and photoreceptor for retinal regeneration has not yet been investigated. In this study, we evaluated the long-term effects of hiPSC-derived RPE and photoreceptor cell transplantation in Pde6b knockout rats to study RP; cells were injected into the subretinal space of the right eyes of rats before the appearance of signs of retinal degeneration at 2–3 weeks of age. Ten months after transplantation, we evaluated the cells using fundus photography, optical coherence tomography, and histological evaluation, and no abnormal cell proliferation was observed. A relatively large number of transplanted cells persisted during the first 4 months; subsequently, the number of these cells decreased gradually. Notably, immunohistochemical analysis revealed that the hiPSC-derived retinal cells showed characteristics of both RPE cells and photoreceptors of human origin after transplantation. Functional analysis of vision by scotopic electroretinogram revealed significant preservation of vision after transplantation. Our study suggests that the transplantation of hiPSC-derived retinal cells, including RPE cells and photoreceptors, has a potential therapeutic effect against irreversible retinal degenerative diseases.


2012 ◽  
Vol 419 (1) ◽  
pp. 130-135 ◽  
Author(s):  
Takuya Uemura ◽  
Kiyohito Takamatsu ◽  
Mikinori Ikeda ◽  
Mitsuhiro Okada ◽  
Kenichi Kazuki ◽  
...  

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