Stem Cell Reports最新文献_第9页

From responsibility to responsibilization in stem cell research: An ethical framework. 干细胞研究从责任到责任：伦理框架。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2025-02-11 Epub Date: 2025-01-09 DOI: 10.1016/j.stemcr.2024.102389

Lars S Assen, Annelien L Bredenoord, Rosario Isasi, Morris A Fabbri, Marianna A Tryfonidou, Karin R Jongsma

引用次数: 0

Chemically defined and dynamic click hydrogels support hair cell differentiation in human inner ear organoids. 化学定义和动态点击水凝胶支持人内耳类器官的毛细胞分化。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2025-02-11 Epub Date: 2025-01-09 DOI: 10.1016/j.stemcr.2024.12.001

Matthew R Arkenberg, Mahboubeh Jafarkhani, Chien-Chi Lin, Eri Hashino

{"title":"Chemically defined and dynamic click hydrogels support hair cell differentiation in human inner ear organoids.","authors":"Matthew R Arkenberg, Mahboubeh Jafarkhani, Chien-Chi Lin, Eri Hashino","doi":"10.1016/j.stemcr.2024.12.001","DOIUrl":"10.1016/j.stemcr.2024.12.001","url":null,"abstract":"The mechanical properties in the inner ear microenvironment play a key role in its patterning during embryonic development. To recapitulate inner ear development in vitro, three-dimensional tissue engineering strategies including the application of representative tissue models and scaffolds are of increasing interest. Human inner ear organoids are a promising model to recapitulate developmental processes; however, the current protocol requires Matrigel that contains ill-defined extracellular matrix components. Here, we implement an alternative, chemically defined, dynamic hydrogel to support the differentiation of human inner ear organoids. Specifically, thiol-norbornene and hydrazide-aldehyde click chemistries are used to fabricate inner ear organoid-laden, gelatin-based scaffolds. We identify optimal formulations to support hair cell development with comparable efficiency and fidelity to Matrigel-cultured organoids. These results suggest that the chemically defined hydrogel may serve as a viable alternative to Matrigel for inner ear tissue engineering.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102386"},"PeriodicalIF":5.9,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11864144/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142967024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Transplantation of genome-edited retinal organoids restores some fundamental physiological functions coordinated with severely degenerated host retinas. 基因组编辑的视网膜类器官移植恢复了与严重退化的宿主视网膜协调的一些基本生理功能。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2025-02-11 Epub Date: 2025-01-16 DOI: 10.1016/j.stemcr.2024.102393

Mikiya Watanabe, Takayuki Yamada, Chieko Koike, Masayo Takahashi, Masao Tachibana, Michiko Mandai

{"title":"Transplantation of genome-edited retinal organoids restores some fundamental physiological functions coordinated with severely degenerated host retinas.","authors":"Mikiya Watanabe, Takayuki Yamada, Chieko Koike, Masayo Takahashi, Masao Tachibana, Michiko Mandai","doi":"10.1016/j.stemcr.2024.102393","DOIUrl":"10.1016/j.stemcr.2024.102393","url":null,"abstract":"We have previously shown that the transplantation of stem cell-derived retinal organoid (RO) sheets into animal models of end-stage retinal degeneration can lead to host-graft synaptic connectivity and restoration of vision, which was further improved using genome-edited Islet1-/- ROs (gROs) with a reduced number of ON-bipolar cells. However, the details of visual function restoration using this regenerative therapeutic approach have not yet been characterized. Here, we evaluated the electrophysiological properties of end-stage rd1 retinas after transplantation (TP-rd1) and compared them with those of wild-type (WT) retinas using multi-electrode arrays. Notably, retinal ganglion cells (RGCs) in TP-rd1 retinas acquired light sensitivity comparable to that of WT retinas. Furthermore, RGCs in TP-rd1 retinas showed light adaptation to a photopic background and responded to flickering stimuli. These results demonstrate that transplantation of gRO sheets may restore some fundamental physiological functions, possibly coordinating with the remaining functions in retinas with end-stage degeneration.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102393"},"PeriodicalIF":5.9,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11864131/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143011922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Selective activation of FZD2 and FZD7 reveals non-redundant function during mesoderm differentiation. FZD2和FZD7的选择性激活揭示了在中胚层分化过程中的非冗余功能。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2025-02-11 Epub Date: 2025-01-16 DOI: 10.1016/j.stemcr.2024.102391

Rony Chidiac, Andy Yang, Elli Kubarakos, Nicholas Mikolajewicz, Hong Han, Maira P Almeida, Pierre E Thibeault, Sichun Lin, Graham MacLeod, Jean-Philippe Gratton, Jason Moffat, Stephane Angers

{"title":"Selective activation of FZD2 and FZD7 reveals non-redundant function during mesoderm differentiation.","authors":"Rony Chidiac, Andy Yang, Elli Kubarakos, Nicholas Mikolajewicz, Hong Han, Maira P Almeida, Pierre E Thibeault, Sichun Lin, Graham MacLeod, Jean-Philippe Gratton, Jason Moffat, Stephane Angers","doi":"10.1016/j.stemcr.2024.102391","DOIUrl":"10.1016/j.stemcr.2024.102391","url":null,"abstract":"During gastrulation, Wnt-β-catenin signaling dictates lineage bifurcation generating different mesoderm cell types. However, the specific role of Wnt receptors in mesoderm specification remains elusive. Using selective Frizzled (FZD) and LRP5/6 antibody-based agonists, we examined FZD receptors' function during directed mesoderm differentiation of human pluripotent stem cells (hPSCs). We found that FZD2 and FZD7 receptors are expressed at the membrane of hPSCs and that their activation triggers β-catenin signaling with different kinetics, thereby influencing mesoderm patterning choices. Specifically, FZD7 activation enhances both paraxial and lateral mesoderm differentiation, whereas FZD2 activation favors paraxial mesoderm. Mechanistically, FZD2 activation promotes sustained Wnt-β-catenin levels, guiding hPSCs differentiation toward paraxial mesoderm, while blocking lateral mesoderm. In contrast, FZD7 activation kinetics display similar initial activation but more dampening of β-catenin signaling, permitting lateral mesoderm induction in addition to paraxial mesoderm specification. Our findings reveal non-redundant roles for FZD2 and FZD7 in mesoderm specification, offering leverage for precise directed differentiation outcomes.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102391"},"PeriodicalIF":5.9,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11864152/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143011920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Capture primed pluripotency in guinea pig. 豚鼠捕获引物多能性。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2025-02-11 Epub Date: 2025-01-09 DOI: 10.1016/j.stemcr.2024.102388

Jing Guo, Runxia Lin, Jinpeng Liu, Rongrong Liu, Shuyan Chen, Zhen Zhang, Yongzheng Yang, Haiyun Wang, Luqin Wang, Shengyong Yu, Chunhua Zhou, Lizhan Xiao, Rongping Luo, Jinjin Yu, Lihua Zeng, Xiaoli Zhang, Yusha Li, Haokaifeng Wu, Tao Wang, Yi Li, Manish Kumar, Ping Zhu, Jing Liu

{"title":"Capture primed pluripotency in guinea pig.","authors":"Jing Guo, Runxia Lin, Jinpeng Liu, Rongrong Liu, Shuyan Chen, Zhen Zhang, Yongzheng Yang, Haiyun Wang, Luqin Wang, Shengyong Yu, Chunhua Zhou, Lizhan Xiao, Rongping Luo, Jinjin Yu, Lihua Zeng, Xiaoli Zhang, Yusha Li, Haokaifeng Wu, Tao Wang, Yi Li, Manish Kumar, Ping Zhu, Jing Liu","doi":"10.1016/j.stemcr.2024.102388","DOIUrl":"10.1016/j.stemcr.2024.102388","url":null,"abstract":"Guinea pigs are valuable models for human disease research, yet the lack of established pluripotent stem cell lines has limited their utility. In this study, we isolate and characterize guinea pig epiblast stem cells (gpEpiSCs) from post-implantation embryos. These cells differentiate into the three germ layers, maintain normal karyotypes, and rely on FGF2 and ACTIVIN A signaling for self-renewal and pluripotency. Wingless/Integrated (WNT) signaling inhibition is also essential for their maintenance. GpEpiSCs express key pluripotency markers (OCT4, SOX2, NANOG) and share transcriptional similarities with human and mouse primed stem cells. While many genes are conserved between guinea pig and human primed stem cells, transcriptional analysis also reveals species-specific differences in pluripotency-related pathways. Epigenetic analysis highlights bivalent gene regulation, underscoring their developmental potential. This work demonstrates both the evolutionary conservation and divergence of primed pluripotent stem cells, providing a new tool for biomedical research and enhancing guinea pigs' utility in studying human diseases.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102388"},"PeriodicalIF":5.9,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11864139/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142967023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Dual inhibition of MAPK/ERK and BMP signaling induces entorhinal-like identity in mouse ESC-derived pallial progenitors. MAPK/ERK和BMP信号的双重抑制诱导小鼠esc来源的苍白祖细胞的内嗅样身份。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2025-02-11 Epub Date: 2025-01-09 DOI: 10.1016/j.stemcr.2024.12.002

Fabrizio Tonelli, Ludovico Iannello, Stefano Gustincich, Angelo Di Garbo, Luca Pandolfini, Federico Cremisi

{"title":"Dual inhibition of MAPK/ERK and BMP signaling induces entorhinal-like identity in mouse ESC-derived pallial progenitors.","authors":"Fabrizio Tonelli, Ludovico Iannello, Stefano Gustincich, Angelo Di Garbo, Luca Pandolfini, Federico Cremisi","doi":"10.1016/j.stemcr.2024.12.002","DOIUrl":"10.1016/j.stemcr.2024.12.002","url":null,"abstract":"The mechanisms that determine distinct embryonic pallial identities remain elusive. The central role of Wnt signaling in directing dorsal telencephalic progenitors to the isocortex or hippocampus has been elucidated. Here, we show that timely inhibition of MAPK/ERK and BMP signaling in neuralized mouse embryonic stem cells (ESCs) specifies a cell identity characteristic of the allocortex. Comparison of the global gene expression profiles of neural cells generated by MAPK/ERK and BMP inhibition (MiBi cells) with those of cells from early postnatal encephalic regions reveals a pallial identity of MiBi cells, distinct from isocortical and hippocampal cells. MiBi cells display a unique pattern of gene expression and connectivity, and share molecular and electrophysiological features with the entorhinal cortex. Our results suggest that early changes in cell signaling can specify distinct pallial fates that are maintained by specific neuronal lineages independent of subsequent embryonic morphogenetic interactions and can determine their functional connectivity.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102387"},"PeriodicalIF":5.9,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11864161/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142967025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A novel rapalog shows improved safety vs. efficacy in a human organoid model of polycystic kidney disease. 一项新的rapalog显示了人类多囊肾病类器官模型的安全性和有效性的提高。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2025-02-11 Epub Date: 2025-01-23 DOI: 10.1016/j.stemcr.2024.102395

Ramila E Gulieva, Parvaneh Ahmadvand, Benjamin S Freedman

引用次数: 0

Effect of Notch1 signaling on muscle engraftment and maturation from pluripotent stem cells. Notch1信号在多能干细胞肌肉移植和成熟中的作用。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2025-02-11 Epub Date: 2025-01-30 DOI: 10.1016/j.stemcr.2024.102396

Aline M S Yamashita, Bayardo I Garay, Hyunkee Kim, Darko Bosnakovski, Juan E Abrahante, Karim Azzag, Phablo Abreu, Aaron Ahlquist, Rita C R Perlingeiro

{"title":"Effect of Notch1 signaling on muscle engraftment and maturation from pluripotent stem cells.","authors":"Aline M S Yamashita, Bayardo I Garay, Hyunkee Kim, Darko Bosnakovski, Juan E Abrahante, Karim Azzag, Phablo Abreu, Aaron Ahlquist, Rita C R Perlingeiro","doi":"10.1016/j.stemcr.2024.102396","DOIUrl":"10.1016/j.stemcr.2024.102396","url":null,"abstract":"Pax3-induced pluripotent stem cell-derived myogenic progenitors display an embryonic molecular signature but become postnatal upon transplantation. Because this correlates with upregulation of Notch signaling, here we probed whether NOTCH1 is required for in vivo maturation by performing gain- and loss-of-function studies in inducible Pax3 (iPax3) myogenic progenitors. Transplantation studies revealed that Notch1 signaling did not change the number of donor-derived fibers; however, the NOTCH1 overexpression cohorts showed enhanced satellite cell engraftment and more mature fibers, as indicated by fewer fibers expressing the embryonic myosin heavy-chain isoform and more type IIX fibers. While donor-derived Pax7+ cells were detected in all transplants, in the absence of Notch1, secondary grafts exhibited a high fraction of these cells in the interstitial space, indicating that NOTCH1 is required for proper satellite cell homing. Transcriptional profiling of NOTCH1-modified donor-derived satellite cells suggests that this may be due to changes in the extracellular matrix organization, cell cycle, and metabolism.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102396"},"PeriodicalIF":5.9,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11864150/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143075590","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Efficient differentiation of human iPSCs into Leydig-like cells capable of long-term stable secretion of testosterone. 人多能干细胞有效分化为能够长期稳定分泌睾酮的leydigi样细胞。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2025-02-11 Epub Date: 2025-01-16 DOI: 10.1016/j.stemcr.2024.102392

Katsuya Sato, Michiyo Koyanagi-Aoi, Keiichiro Uehara, Yosuke Yamashita, Masakazu Shinohara, Suji Lee, Anika Reinhardt, Knut Woltjen, Koji Chiba, Hideaki Miyake, Masato Fujisawa, Takashi Aoi

{"title":"Efficient differentiation of human iPSCs into Leydig-like cells capable of long-term stable secretion of testosterone.","authors":"Katsuya Sato, Michiyo Koyanagi-Aoi, Keiichiro Uehara, Yosuke Yamashita, Masakazu Shinohara, Suji Lee, Anika Reinhardt, Knut Woltjen, Koji Chiba, Hideaki Miyake, Masato Fujisawa, Takashi Aoi","doi":"10.1016/j.stemcr.2024.102392","DOIUrl":"10.1016/j.stemcr.2024.102392","url":null,"abstract":"Late-onset hypogonadism (LOH) syndrome is characterized by age-related testosterone deficiency and negatively affects the quality of life of older men. A promising therapeutic approach for LOH syndrome is transplantation of testosterone-producing Leydig-like cells (LLCs) derived from human induced pluripotent stem cells (hiPSCs). However, previous studies have encountered obstacles, such as limited cell longevity, insufficient testosterone production, and inefficiency of differentiation. To address these issues, we developed a novel protocol that includes forced NR5A1 expression, a cytokine cocktail promoting mesoderm differentiation, and a transitional shift from 3D to 2D cultures. The resultant cells survived on culture dishes for over 16 weeks, produced 22-fold more testosterone than the conventional method, and constituted a homogeneous population of LLCs with a differentiation efficiency exceeding 99% without purification. Furthermore, these LLCs were successfully engrafted subcutaneously into mice, resulting in increased serum testosterone levels. Our study will facilitate innovative therapeutic strategies for LOH syndrome.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102392"},"PeriodicalIF":5.9,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11864132/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143011921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Microvessel co-transplantation improves poor remuscularization by hiPSC-cardiomyocytes in a complex disease model of myocardial infarction and type 2 diabetes. 微血管共移植改善了hipsc -心肌细胞在心肌梗死和2型糖尿病复杂疾病模型中的再肌化不良。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2025-02-11 Epub Date: 2025-01-23 DOI: 10.1016/j.stemcr.2024.102394

Xuetao Sun, Jun Wu, Omar Mourad, Renke Li, Sara S Nunes

{"title":"Microvessel co-transplantation improves poor remuscularization by hiPSC-cardiomyocytes in a complex disease model of myocardial infarction and type 2 diabetes.","authors":"Xuetao Sun, Jun Wu, Omar Mourad, Renke Li, Sara S Nunes","doi":"10.1016/j.stemcr.2024.102394","DOIUrl":"10.1016/j.stemcr.2024.102394","url":null,"abstract":"People with type 2 diabetes (T2D) are at a higher risk for myocardial infarction (MI) than age-matched healthy individuals. Here, we studied cell-based cardiac regeneration post MI in T2D rats modeling the co-morbid conditions in patients with MI. We recapitulated the T2D hallmarks and clinical aspects of diabetic cardiomyopathy using high-fat diet and streptozotocin in athymic rats, which were then subjected to MI and intramyocardial implantation of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) with or without rat adipose-derived microvessels (MVs). hiPSC-CM alone engrafted poorly. Co-delivery of hiPSC-CMs with MVs yielded a smaller infarct area and a thicker left ventricle wall. Additionally, MVs robustly integrated into the infarcted hearts, improved the survival of hiPSC-CMs, and improved cardiac function. MV-conditioned media also promoted hiPSC-CM maturation in vitro, increasing cardiomyocyte (CM) size in an interleukin (IL)-6-dependent manner. Given the availability of MVs from human adipose tissue, MVs present great translational potential for the treatment of heart failure in people with T2D.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102394"},"PeriodicalIF":5.9,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11864147/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143042257","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0