Novel artificial nerve transplantation of human iPSC-derived neurite bundles enhanced nerve regeneration after peripheral nerve injury

Takayuki Nishijima, Kentaro Okuyama, Shinsuke Shibata, Hiroo Kimura, Munehisa Shinozaki, Takehito Ouchi, Yo Mabuchi, Tatsukuni Ohno, Junpei Nakayama, Manabu Hayatsu, Keiko Uchiyama, Tomoko Shindo, Eri Niiyama, Sayaka Toita, Jiro Kawada, Takuji Iwamoto, Masaya Nakamura, Hideyuki Okano, Narihito Nagoshi

研究成果: ジャーナルへの寄稿学術論文査読

抄録

Background: Severe peripheral nerve damage always requires surgical treatment. Autologous nerve transplantation is a standard treatment, but it is not sufficient due to length limitations and extended surgical time. Even with the available artificial nerves, there is still large room for improvement in their therapeutic effects. Novel treatments for peripheral nerve injury are greatly expected. Methods: Using a specialized microfluidic device, we generated artificial neurite bundles from human iPSC-derived motor and sensory nerve organoids. We developed a new technology to isolate cell-free neurite bundles from spheroids. Transplantation therapy was carried out for large nerve defects in rat sciatic nerve with novel artificial nerve conduit filled with lineally assembled sets of human neurite bundles. Quantitative comparisons were performed over time to search for the artificial nerve with the therapeutic effect, evaluating the recovery of motor and sensory functions and histological regeneration. In addition, a multidimensional unbiased gene expression profiling was carried out by using next-generation sequencing. Result: After transplantation, the neurite bundle-derived artificial nerves exerted significant therapeutic effects, both functionally and histologically. Remarkably, therapeutic efficacy was achieved without immunosuppression, even in xenotransplantation. Transplanted neurite bundles fully dissolved after several weeks, with no tumor formation or cell proliferation, confirming their biosafety. Posttransplant gene expression analysis highlighted the immune system’s role in recovery. Conclusion: The combination of newly developed microfluidic devices and iPSC technology enables the preparation of artificial nerves from organoid-derived neurite bundles in advance for future treatment of peripheral nerve injury patients. A promising, safe, and effective peripheral nerve treatment is now ready for clinical application.

本文言語英語
論文番号6
ジャーナルInflammation and Regeneration
44
1
DOI
出版ステータス出版済み - 12-2024

All Science Journal Classification (ASJC) codes

  • 免疫アレルギー学
  • 免疫学
  • 細胞生物学

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