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Challenges and opportunities for human Organ Chips in FDA assessments and pharma pipelines, 人体器官芯片在FDA评估和制药管道中的挑战和机遇
IF 23.9 1区 医学
Cell stem cell Pub Date : 2026-01-20 DOI: 10.1016/j.stem.2025.12.022
Donald E. Ingber
{"title":"Challenges and opportunities for human Organ Chips in FDA assessments and pharma pipelines,","authors":"Donald E. Ingber","doi":"10.1016/j.stem.2025.12.022","DOIUrl":"https://doi.org/10.1016/j.stem.2025.12.022","url":null,"abstract":"","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"5 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146014811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Activation of a branched-chain amino acid rheostat restores replication-dependent hematopoietic stem cell fitness 支链氨基酸变阻器的激活可以恢复依赖复制的造血干细胞的适应性
IF 23.9 1区 医学
Cell stem cell Pub Date : 2026-01-13 DOI: 10.1016/j.stem.2025.12.018
James Bartram, Sydney Treichel, Baobao Annie Song, Juying Xu, Devyani Sharma, Waseem Nasr, Madeline Frangiosa, Andrew Harley, Travis Nemkov, Angelo D’Alessandro, Nathan Salomonis, H. Leighton Grimes, Marie-Dominique Filippi
{"title":"Activation of a branched-chain amino acid rheostat restores replication-dependent hematopoietic stem cell fitness","authors":"James Bartram, Sydney Treichel, Baobao Annie Song, Juying Xu, Devyani Sharma, Waseem Nasr, Madeline Frangiosa, Andrew Harley, Travis Nemkov, Angelo D’Alessandro, Nathan Salomonis, H. Leighton Grimes, Marie-Dominique Filippi","doi":"10.1016/j.stem.2025.12.018","DOIUrl":"https://doi.org/10.1016/j.stem.2025.12.018","url":null,"abstract":"","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"92 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145962371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Nanoengineered extrusion-aligned tract bioprinting enables functional repair of spinal cord injuries 纳米工程挤压排列束生物打印使脊髓损伤的功能性修复成为可能
IF 23.9 1区 医学
Cell stem cell Pub Date : 2026-01-13 DOI: 10.1016/j.stem.2025.12.021
Wenhui Huang, Shuxian Chen, Kai Li, Yali Ding, Bo Zhan, Diming Zhao, Guoshi Xu, Haitao Guo, Chengyi Sun, Rui Yuan, Hao Gu, Juan Zhang, Kai Guo, Jun Wu, Jianwu Dai, Wei Li, Xiongfei Zheng, Guihai Feng, Baoyang Hu, Qi Gu
{"title":"Nanoengineered extrusion-aligned tract bioprinting enables functional repair of spinal cord injuries","authors":"Wenhui Huang, Shuxian Chen, Kai Li, Yali Ding, Bo Zhan, Diming Zhao, Guoshi Xu, Haitao Guo, Chengyi Sun, Rui Yuan, Hao Gu, Juan Zhang, Kai Guo, Jun Wu, Jianwu Dai, Wei Li, Xiongfei Zheng, Guihai Feng, Baoyang Hu, Qi Gu","doi":"10.1016/j.stem.2025.12.021","DOIUrl":"https://doi.org/10.1016/j.stem.2025.12.021","url":null,"abstract":"","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"30 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145962370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Development of human induced pluripotent stem cell-derived ovarian support cells as a clinical-grade product for in vitro fertilization 人类诱导多能干细胞衍生的卵巢支持细胞作为体外受精的临床级产品的开发
IF 23.9 1区 医学
Cell stem cell Pub Date : 2026-01-13 DOI: 10.1016/j.stem.2025.12.020
Bruna Paulsen, Ferran Barrachina, Sabrina Piechota, Alexander D. Noblett, Mark Johnson, Simone Kats, Cassandra Lew, Maria Marchante, Alexandra B. Figueroa, Itzel Garcia Granada, Elizabeth Ingalls Lopez, Erick Martinez, Paula Ricra, Camila Carlos, Jazmin Meza, Wendy Montanchez, Pilar Pino, Cesar Reategui, Enrique Noriega, Alicia Elias, Luis Noriega-Portella, Gus Haddad, Dina Radenkovic, Eugenia Moran, Pamela Villanueva, Jose Guiterrez, Luis Guzman, Pietro Bortolleto, David F. Albertini, Michel De Vos, Christian C. Kramme
{"title":"Development of human induced pluripotent stem cell-derived ovarian support cells as a clinical-grade product for in vitro fertilization","authors":"Bruna Paulsen, Ferran Barrachina, Sabrina Piechota, Alexander D. Noblett, Mark Johnson, Simone Kats, Cassandra Lew, Maria Marchante, Alexandra B. Figueroa, Itzel Garcia Granada, Elizabeth Ingalls Lopez, Erick Martinez, Paula Ricra, Camila Carlos, Jazmin Meza, Wendy Montanchez, Pilar Pino, Cesar Reategui, Enrique Noriega, Alicia Elias, Luis Noriega-Portella, Gus Haddad, Dina Radenkovic, Eugenia Moran, Pamela Villanueva, Jose Guiterrez, Luis Guzman, Pietro Bortolleto, David F. Albertini, Michel De Vos, Christian C. Kramme","doi":"10.1016/j.stem.2025.12.020","DOIUrl":"https://doi.org/10.1016/j.stem.2025.12.020","url":null,"abstract":"","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"265 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145962526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Retinal ganglion cell survival and functional maturation in transiently vascularized human retinal organoids. 短暂血管化人视网膜类器官视网膜神经节细胞存活和功能成熟。
IF 23.9 1区 医学
Cell stem cell Pub Date : 2026-01-12 DOI: 10.1016/j.stem.2025.12.013
Kritika Sharma,Rouhollah Habibey,Mariana M Ribeiro,Bohao Cui,Rebecca A Siwicki,Johannes Striebel,Julia S Pawlick,Jasmin Zorn,Larissa Utz,Magdalena Renner,Simone Picelli,Frank G Holz,Carmen Ruiz de Almodóvar,Cameron S Cowan,Volker Busskamp
{"title":"Retinal ganglion cell survival and functional maturation in transiently vascularized human retinal organoids.","authors":"Kritika Sharma,Rouhollah Habibey,Mariana M Ribeiro,Bohao Cui,Rebecca A Siwicki,Johannes Striebel,Julia S Pawlick,Jasmin Zorn,Larissa Utz,Magdalena Renner,Simone Picelli,Frank G Holz,Carmen Ruiz de Almodóvar,Cameron S Cowan,Volker Busskamp","doi":"10.1016/j.stem.2025.12.013","DOIUrl":"https://doi.org/10.1016/j.stem.2025.12.013","url":null,"abstract":"Retinal organoids are widely used to model human retinal development and disease, but their utility is limited by the absence of vascular networks and stable axonal projections, which contribute to retinal ganglion cell degeneration and loss of function. To address these challenges, we incorporated stem cell-derived endothelial cells to induce transient vascular-like networks and used microfluidic devices to stabilize axonal growth. The resulting organoids showed reduced hypoxia, increased size, and decreased apoptosis, indicating improved long-term survival and maturation of retinal ganglion cells. Integration with microfluidic-microelectrode arrays enabled stable recordings of spontaneous and optogenetically evoked activity, which persisted beyond the time when control organoids lost function. At later stages, these transiently vascularized organoids displayed photoreceptor-driven ON, OFF, and ON-OFF light responses, indicating circuit-level retinal activity. This bioengineered platform establishes a long-term, functional model of the human retina as a transformative tool for retinal research and therapeutic innovation.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"12 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145961381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Human pluripotent stem cell-derived innate and adaptive immune cells for cancer immunotherapy. 人类多能干细胞衍生的先天性和适应性免疫细胞用于癌症免疫治疗。
IF 23.9 1区 医学
Cell stem cell Pub Date : 2026-01-08 DOI: 10.1016/j.stem.2025.12.017
Zahir Shah,Lei Tian,Michael A Caligiuri,Dan S Kaufman,Jianhua Yu
{"title":"Human pluripotent stem cell-derived innate and adaptive immune cells for cancer immunotherapy.","authors":"Zahir Shah,Lei Tian,Michael A Caligiuri,Dan S Kaufman,Jianhua Yu","doi":"10.1016/j.stem.2025.12.017","DOIUrl":"https://doi.org/10.1016/j.stem.2025.12.017","url":null,"abstract":"Allogeneic cell-based therapies hold great promise for cancer immunotherapy but face challenges like scalability, immune rejection, graft-versus-host disease, and toxicities. Human pluripotent stem cells (hPSCs), including embryonic and induced pluripotent stem cells (iPSCs), offer a scalable and adaptable platform to address these limitations. hPSCs provide an inexhaustible source of immune cells that can be genetically modified at the single-cell level to enhance anti-tumor activity and reduce immunogenicity. Recent advancements in generating iPSC-derived natural killer (NK) cells, T cells, and macrophages are opening the door to safer and more effective immunotherapies. This review examines the progress, challenges, and future directions in utilizing hPSC-derived immune cells to enhance cancer treatment and overcome barriers in allogeneic therapy.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"5 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145937748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A sculptor of modern regenerative medicine. 现代再生医学的雕刻家。
IF 23.9 1区 医学
Cell stem cell Pub Date : 2026-01-08 DOI: 10.1016/j.stem.2025.12.014
Sarah Stanley
{"title":"A sculptor of modern regenerative medicine.","authors":"Sarah Stanley","doi":"10.1016/j.stem.2025.12.014","DOIUrl":"https://doi.org/10.1016/j.stem.2025.12.014","url":null,"abstract":"Editors' note: The Ogawa-Yamanaka Stem Cell Prize recognizes groundbreaking work in translational regenerative medicine using reprogrammed cells. The prize is supported by Gladstone Institutes, in partnership with Cell Press. Among his myriad accomplishments, Rudolf Jaenisch-winner of the 2025 Ogawa-Yamanaka Stem Cell Prize-was the first to demonstrate the potential of induced pluripotent stem cells to treat disease.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"3 1","pages":"10-12"},"PeriodicalIF":23.9,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145937749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Transcriptional code for circuit integration in the injured brain by transplanted human neurons. 移植的人神经元损伤脑内电路整合的转录编码。
IF 23.9 1区 医学
Cell stem cell Pub Date : 2026-01-08 DOI: 10.1016/j.stem.2025.12.008
Zhifu Wang,Danyi Zheng,Shu-Min Chou,Phil Jun Kang,Fei Ye,Su-Chun Zhang
{"title":"Transcriptional code for circuit integration in the injured brain by transplanted human neurons.","authors":"Zhifu Wang,Danyi Zheng,Shu-Min Chou,Phil Jun Kang,Fei Ye,Su-Chun Zhang","doi":"10.1016/j.stem.2025.12.008","DOIUrl":"https://doi.org/10.1016/j.stem.2025.12.008","url":null,"abstract":"Neural transplantation holds the potential to repair damaged neural circuits in neurological diseases. However, it remains unknown how the grafted neurons project axons to and make functional connections with the appropriate targets to repair the damaged circuit at the adult stage. Here, we report that human cortical progenitors, transplanted into the ischemic mouse motor cortex, matured and integrated into cortical and subcortical neural circuits, including the corticospinal tract. Neuronal tracing combined with single-nuclei RNA sequencing revealed the close relationship between the transcription profiles of a cortical neuronal subtype, especially those of axon guidance and synapse assembly, with the specific target projection and synapse organization. Machine learning-based regression further identified the transcriptional codes for the targeted projection and circuit integration to reconstruct the damaged circuits. Our finding opens a promising strategy for treating neurological diseases through promoting regeneration and neural transplantation.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"397 1","pages":"44-57.e7"},"PeriodicalIF":23.9,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145937751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Two isoforms, two outcomes: How NTRK2 shapes vascular regeneration. 两种亚型，两种结果：NTRK2如何影响血管再生。
IF 23.9 1区 医学
Cell stem cell Pub Date : 2026-01-08 DOI: 10.1016/j.stem.2025.12.003
Yun Zhao,Xi Wang,Kai Wang
{"title":"Two isoforms, two outcomes: How NTRK2 shapes vascular regeneration.","authors":"Yun Zhao,Xi Wang,Kai Wang","doi":"10.1016/j.stem.2025.12.003","DOIUrl":"https://doi.org/10.1016/j.stem.2025.12.003","url":null,"abstract":"In this issue of Cell Stem Cell, Zhang et al. identify a pathological NTRK2 isoform switch in bronchopulmonary dysplasia that alters the regenerative capacity of capillary endothelial cells, highlighting isoform-specific targeting as a promising strategy for vascular repair.1.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"244 1","pages":"7-9"},"PeriodicalIF":23.9,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145937753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Nanoengineered 3D culture substrate enables superior persistence and polyclonal engraftment of genetically engineered hematopoietic stem cells 纳米工程三维培养基质使基因工程造血干细胞具有优异的持久性和多克隆植入性
IF 23.9 1区 医学
Cell stem cell Pub Date : 2026-01-08 DOI: 10.1016/j.stem.2025.12.016
Federico Midena, Laura Alessandrini, Claudio Conci, Matteo Barcella, Francesco Gazzo, Emanuela Jacchetti, Edoardo Carsana, Fabrizio Benedicenti, Roberta Vacca, Lucrezia della Volpe, Sergio Arévalo, Kety Giannetti, Dafne Barozzi, Martina Franchino, Erika Zonari, Francesca Ferrua, Giacomo Farina, Chiara Brombin, Federica Cugnata, Martina Fiumara, Raffaella Di Micco
{"title":"Nanoengineered 3D culture substrate enables superior persistence and polyclonal engraftment of genetically engineered hematopoietic stem cells","authors":"Federico Midena, Laura Alessandrini, Claudio Conci, Matteo Barcella, Francesco Gazzo, Emanuela Jacchetti, Edoardo Carsana, Fabrizio Benedicenti, Roberta Vacca, Lucrezia della Volpe, Sergio Arévalo, Kety Giannetti, Dafne Barozzi, Martina Franchino, Erika Zonari, Francesca Ferrua, Giacomo Farina, Chiara Brombin, Federica Cugnata, Martina Fiumara, Raffaella Di Micco","doi":"10.1016/j.stem.2025.12.016","DOIUrl":"https://doi.org/10.1016/j.stem.2025.12.016","url":null,"abstract":"<em>Ex vivo</em> culture of hematopoietic stem and progenitor cells (HSPCs) is required for gene therapy applications but inadvertently triggers detrimental cellular responses, potentially threatening clinical success. In this study, we employ nichoids, biocompatible 3D culture substrates with cell-scale resolution, to provide HSPCs with mechanical support during <em>ex vivo</em> manipulation. This innovative 3D system improves HSPC multi-lineage differentiation and engraftment capacity by leveraging mechanobiological control over nuclear morphology, cytoskeleton organization, metabolism, and DNA integrity. Notably, 3D culture enables efficient genetic engineering across multiple platforms, including long-range gene editing, base- and prime-editing, and lentiviral-mediated gene addition. Moreover, this scaffold increases the clonal output and persistence of genetically engineered cells in xenotransplantation experiments, including a clinical protocol for lentiviral gene addition in Wiskott-Aldrich syndrome. Overall, we propose a transformative approach to enhance the efficacy and safety of emerging and established hematopoietic stem cell-based gene therapy applications.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"44 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145937535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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