担当区分：筆頭著者   掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Science and Business Media LLC  

Abstract

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.

DOI： 10.1186/s41232-024-00319-4

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その他リンク： https://link.springer.com/article/10.1186/s41232-024-00319-4/fulltext.html

掲載種別：研究論文（学術雑誌）   出版者・発行元：Wiley  

DOI： 10.1111/jdv.19357

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

Mitophagy plays an important role in mitochondrial homeostasis by selective degradation of mitochondria. During mitophagy, mitochondria should be fragmented to allow engulfment within autophagosomes, whose capacity is exceeded by the typical mitochondria mass. However, the known mitochondrial fission factors, dynamin-related proteins Dnm1 in yeasts and DNM1L/Drp1 in mammals, are dispensable for mitophagy. Here, we identify Atg44 as a mitochondrial fission factor that is essential for mitophagy in yeasts, and we therefore term Atg44 and its orthologous proteins mitofissin. In mitofissin-deficient cells, a part of the mitochondria is recognized by the mitophagy machinery as cargo but cannot be enwrapped by the autophagosome precursor, the phagophore, due to a lack of mitochondrial fission. Furthermore, we show that mitofissin directly binds to lipid membranes and brings about lipid membrane fragility to facilitate membrane fission. Taken together, we propose that mitofissin acts directly on lipid membranes to drive mitochondrial fission required for mitophagy.

DOI： 10.1016/j.molcel.2023.04.022

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担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

Squamate reptiles rely on the vomeronasal organ for chemoperception of their environment. This organ functionally associates with several structures, such as the nasolacrimal duct and choanal groove, which are morphologically diverse among species. In this study, we investigated the morphological characteristics and embryogenesis of the vomeronasal organ and its associated structures in the Japanese Grass Lizard (Takydromus tachydromoides). Separation of the complex of the nasolacrimal duct from the vomeronasal organ was observed in this species, a characteristic morphological feature among squamates. Additionally, we integrated the morphological characteristics of the vomeronasal organ and associated structures among squamates, focusing on topological relationships among the structures. The parsimony and likelihood methods for ancestral state reconstruction suggested the parallelism of several morphological characteristics during the evolutionary history of squamates: loss or reduction of the choanal groove, fusion between the nasolacrimal duct and choanal groove, and separation of the nasolacrimal duct from the vomeronasal organ.

DOI： 10.1643/h2020163

Scopus

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Herpetological Society of Japan  

The Japanese grass lizard, Takydromus tachydromoides, is a species endemic to Japan. While several studies have investigated the reproductive ecology of T. tachydromoides, the embryogenesis of this species has not been reported in detail. In the current study, we observed the external morphological characteristics of 247 embryo specimens that developed under a constant temperature (28°C) throughout the duration from oviposition to hatching. We identified 17 consecutive developmental stages for the post-ovipositional developmental process of this species based on the staging criteria that have been widely used for the description of embryogenesis of lizards. The youngest embryos on the day of oviposition corresponded to stage 26, which is a relatively early period in pharyngula stages, and juveniles hatched at stage 42, approximately 30 days after oviposition. The entire developmental sequence of key morphological features was shared with other species of Lacertidae, except for the timing of the beginning of the first body pigmentation. This is the first description of the complete sequence of post-ovipositional developmental stages for the oviparous species of Lacertidae, providing valuable information for further evolutionary developmental studies.

DOI： 10.5358/HSJ.40.66

Scopus

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記述言語：日本語   出版者・発行元：公益社団法人 日本顕微鏡学会  

近年注目される電子顕微鏡用の連続切片を三次元的に解析可能なATUM-SEM法は，樹脂包埋試料のSEM観察法の中でも特に広い範囲の生体構造を高解像度観察が可能であることや，繰り返し切片の観察ができることなど優れた特徴を有する手法である．さらにこの手法で作製された連続切片の観察に，61本のビームを並行照射してイメージングするマルチビームSEMを用いることにより試料の全体像を素早くかつ高分解能で画像化することができ，ミクロレベルのオーダーからナノレベルのオーダーまでの試料の三次元的な構造解析が実施可能となる．最近ではマルチビームSEMとCLEM法を組み合わせた解析により，特定分子の局在を広範囲の切片上にて可視化することができている．本解説ではATUM-SEM法，マルチビームSEMを使った広範囲試料の解析法を概説し，さらにマルチビームSEMによる広範囲CLEM法のイメージング技術についても述べる．

DOI： 10.11410/kenbikyo.56.3_124

CiNii Article

CiNii Books

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その他リンク： https://search.jamas.or.jp/link/ui/2022162912

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会議種別：口頭発表（一般）  

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会議種別：口頭発表（一般）  

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会議種別：ポスター発表  

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