{"id":"hum0472","version":1,"url":"https://humandbs.dbcls.jp/research/hum0472/v1","datePublished":"2024-08-23","versions":[{"version":1,"datePublished":"2024-08-23"}],"title":{"ja":"iPS細胞を用いた大脳皮質神経細胞製剤の開発に向けた非臨床研究","en":"Non-clinical research for the development of neuronal cells from human iPS cell derived cerebral cortical organoid"},"summary":{"aims":{"ja":"脳梗塞や外傷等により傷害された大脳皮質神経細胞は、原則回復せず、運動麻痺などの後遺症が永続する。治療方法の一つとして、多能性幹細胞から分化誘導した神経細胞の移植が考えられる。これまで、ヒトES細胞を用いて大脳オルガノイドを分化誘導可能であることを示したが、臨床応用には、HLAを適合させた他家移植が可能である点において、ヒトiPS細胞の使用が望まれる。本研究では、ヒトiPS細胞を用いた大脳皮質神経細胞製剤の開発に必要な、ヒトiPS細胞から大脳皮質神経細胞への分化誘導方法の確立や、当該分化細胞の安全性・有効性の確認等の非臨床試験を行う。また、将来の産業化を見据えた大量培養や自動化の検討を行う。","en":"When cerebral cortical neurons are damaged due to stroke or trauma, the injured neurons typically do not recover, resulting in persistent sequelae such as motor paralysis. One potential therapeutic approach is the transplantation of neurons derived from pluripotent stem cells. While we have demonstrated that cerebral organoids can be differentiated from human ES cells, using human iPS cells is more desirable for clinical applications due to the possibility of allogeneic transplantation with HLA compatibility. Here, we will perform non-clinical trials to establish differentiation protocols from hiPSCs to cerebral cortical neurons and assess the safety and efficacy of these differentiated cells. Additionally, we will explore large-scale cell production for future industrialization."},"methods":{"ja":"オルガノイドをNeuron Dissociation Solutionsを用いて単一細胞に分散後、10%（v/v）KSRと10μM Y-27632を添加したHBSSで再懸濁した（1,000細胞/µL）。細胞懸濁液をChromium Next GEM Chip G（2000177 10X Genomics）にロードし、ChromiumコントローラでGel Beads-in-Emulsionを得るために処理した（標的細胞数3000細胞）。ライブラリ調製後、RNA-seqを行った。","en":"Organoids were dissociated into single cells with Neuron Dissociation Solutions. Dissociated cells were re-suspended with HBSS supplemented with 10% (v/v) KSR and 10μM Y-27632 at 1,000 cells/µL density. Cell suspension was loaded onto a Chromium Next GEM Chip G (2000177 10X Genomics), targeting 3,000 cells for capture per well, and processed in the Chromium controller to obtain Gel Beads-in-Emulsion. Libraries were generated and RNA-seq was performed."},"targets":{"ja":"健常者1名の末梢血から樹立されたiPS細胞から大脳皮質神経細胞に分化誘導して作製したオルガノイド","en":"Organoids derived from induced pluripotent stem cells of a single healthy individual."},"url":{"ja":null,"en":null}},"listingSummary":{"methods":{"ja":"発現","en":"Expression profiling"},"targets":{"ja":"健常者1名から樹立されたiPS細胞から分化誘導したオルガノイド：9個\n（細胞株）","en":"Organoids derived from iPS cells of a single healthy individual: 9 samples\n(Cell-line)"},"typeOfData":{"ja":"NGS\n（scRNA-seq）","en":"NGS\n(scRNA-seq)"}},"releaseNote":{"ja":"健常者1名から樹立されたiPS細胞から分化誘導したオルガノイドから抽出したRNAを用いたscRNA-seq解析データをfastqファイルにて提供する。","en":"RNAs extracted from organoids derived from iPS cells of a single healthy individual were used for single-cell RNA-sequencing analysis. Fastq files are provided."},"dataProviders":[{"name":{"ja":"髙橋 淳","en":"Jun Takahashi"},"organization":{"name":{"ja":"京都大学 iPS細胞研究所 臨床応用研究部門 神経再生研究分野","en":"Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University"}}}],"researchProjects":[],"grants":[{"title":{"ja":"iPS細胞を用いた脳梗塞治療実現のための応用研究","en":"Translational study for iPS cell-based therapy for stroke"},"agency":{"ja":"日本医療研究開発機構（AMED） 再生・細胞医療・遺伝子治療実現加速化プログラム","en":"Acceleration Program of R&D and Implementation for Regenerative Medicine and Cell and Gene Therapy, Japan Agency for Medical Research and Development (AMED)"},"grantIds":["JP23bm1223005"]},{"title":{"ja":"脳梗塞に対するiPS細胞由来大脳皮質神経細胞移植の開発","en":"Study of iPS cell-based therapy for stroke"},"agency":{"ja":"日本医療研究開発機構（AMED） 橋渡し研究プログラム","en":"Japan Agency for Medical Research and Development (AMED)"},"grantIds":["JP24ym0126160"]}],"relatedPublications":[{"title":"Validation of non-invasive morphology-based selection of cerebral cortical organoids by paired morphological and single-cell RNA sequencing analyses","doi":"https://doi.org/10.1016/j.stemcr.2024.09.005","datasets":["JGAD000859"]}],"datasets":["JGAD000859"],"controlledAccessUsers":[]}