Cell stem cell最新文献_第7页

Primitive macrophages enable long-term vascularization of human heart-on-a-chip platforms 原始巨噬细胞实现了人体心脏芯片平台的长期血管化

IF 23.9 1区医学

Cell stem cell Pub Date : 2024-06-21 DOI: 10.1016/j.stem.2024.05.011

Shira Landau, Yimu Zhao, Homaira Hamidzada, Gregory M. Kent, Sargol Okhovatian, Rick Xing Ze Lu, Chuan Liu, Karl T. Wagner, Krisco Cheung, Sarah A. Shawky, Daniel Vosoughi, Erika Leigh Beroncal, Ian Fernandes, Carolyn L. Cummins, Ana C. Andreazza, Gordon M. Keller, Slava Epelman, Milica Radisic

{"title":"Primitive macrophages enable long-term vascularization of human heart-on-a-chip platforms","authors":"Shira Landau, Yimu Zhao, Homaira Hamidzada, Gregory M. Kent, Sargol Okhovatian, Rick Xing Ze Lu, Chuan Liu, Karl T. Wagner, Krisco Cheung, Sarah A. Shawky, Daniel Vosoughi, Erika Leigh Beroncal, Ian Fernandes, Carolyn L. Cummins, Ana C. Andreazza, Gordon M. Keller, Slava Epelman, Milica Radisic","doi":"10.1016/j.stem.2024.05.011","DOIUrl":"https://doi.org/10.1016/j.stem.2024.05.011","url":null,"abstract":"The intricate anatomical structure and high cellular density of the myocardium complicate the bioengineering of perfusable vascular networks within cardiac tissues. In vivo neonatal studies highlight the key role of resident cardiac macrophages in post-injury regeneration and angiogenesis. Here, we integrate human pluripotent stem-cell-derived primitive yolk-sac-like macrophages within vascularized heart-on-chip platforms. Macrophage incorporation profoundly impacted the functionality and perfusability of microvascularized cardiac tissues up to 2 weeks of culture. Macrophages mitigated tissue cytotoxicity and the release of cell-free mitochondrial DNA (mtDNA), while upregulating the secretion of pro-angiogenic, matrix remodeling, and cardioprotective cytokines. Bulk RNA sequencing (RNA-seq) revealed an upregulation of cardiac maturation and angiogenesis genes. Further, single-nuclei RNA sequencing (snRNA-seq) and secretome data suggest that macrophages may prime stromal cells for vascular development by inducing insulin like growth factor binding protein 7 (IGFBP7) and hepatocyte growth factor (HGF) expression. Our results underscore the vital role of primitive macrophages in the long-term vascularization of cardiac tissues, offering insights for therapy and advancing heart-on-a-chip technologies.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"7 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141436026","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

Bioengineered human colon organoids with in vivo-like cellular complexity and function 具有类似活体细胞复杂性和功能的生物工程人结肠器官组织

IF 23.9 1区医学

Cell stem cell Pub Date : 2024-06-13 DOI: 10.1016/j.stem.2024.05.007

Olga Mitrofanova, Mikhail Nikolaev, Quan Xu, Nicolas Broguiere, Irineja Cubela, J. Gray Camp, Michael Bscheider, Matthias P. Lutolf

{"title":"Bioengineered human colon organoids with in vivo-like cellular complexity and function","authors":"Olga Mitrofanova, Mikhail Nikolaev, Quan Xu, Nicolas Broguiere, Irineja Cubela, J. Gray Camp, Michael Bscheider, Matthias P. Lutolf","doi":"10.1016/j.stem.2024.05.007","DOIUrl":"https://doi.org/10.1016/j.stem.2024.05.007","url":null,"abstract":"Organoids and organs-on-a-chip have emerged as powerful tools for modeling human gut physiology and disease in vitro. Although physiologically relevant, these systems often lack the environmental milieu, spatial organization, cell type diversity, and maturity necessary for mimicking human intestinal mucosa. To instead generate models closely resembling in vivo tissue, we herein integrated organoid and organ-on-a-chip technology to develop an advanced human organoid model, called “mini-colons.” By employing an asymmetric stimulation with growth factors, we greatly enhanced tissue longevity and replicated in vivo-like diversity and patterning of proliferative and differentiated cell types. Mini-colons contain abundant mucus-producing goblet cells and, signifying mini-colon maturation, single-cell RNA sequencing reveals emerging mature and functional colonocytes. This methodology is expanded to generate microtissues from the small intestine and incorporate additional microenvironmental components. Finally, our bioengineered organoids provide a precise platform to systematically study human gut physiology and pathology, and a reliable preclinical model for drug safety assessment.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"70 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2024-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141315832","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

Complete Meiosis from Embryonic Stem Cell-Derived Germ Cells In Vitro 胚胎干细胞衍生生殖细胞的体外完全减数分裂

IF 23.9 1区医学

Cell stem cell Pub Date : 2024-06-11 DOI: 10.1016/j.stem.2024.06.005

Quan Zhou, Mei Wang, Yan Yuan, Xuepeng Wang, Rui Fu, Haifeng Wan, Mingming Xie, Mingxi Liu, Xuejiang Guo, Ying Zheng, Guihai Feng, Qinghua Shi, Xiao-Yang Zhao, Jiahao Sha, Qi Zhou

引用次数: 0

From stem cells to regulatory T cells: A tale of plasticity 从干细胞到调节性 T 细胞：可塑性的故事

IF 23.9 1区医学

Cell stem cell Pub Date : 2024-06-06 DOI: 10.1016/j.stem.2024.05.002

Mehek Ningoo, Miguel Fribourg

引用次数: 0

Greasing the machinery toward maturation of stem cell-derived β cells 为干细胞衍生β细胞的成熟提供润滑剂

IF 23.9 1区医学

Cell stem cell Pub Date : 2024-06-06 DOI: 10.1016/j.stem.2024.05.001

Christos Karampelias, Heiko Lickert

引用次数: 0

CAR macrophages tuning the immune symphony of anti-cancer therapies CAR 巨噬细胞调节抗癌疗法的免疫交响乐

IF 23.9 1区医学

Cell stem cell Pub Date : 2024-06-06 DOI: 10.1016/j.stem.2024.05.006

Daniela Paasch, Nico Lachmann

引用次数: 0

Human iPSC-derived CD4+ Treg-like cells engineered with chimeric antigen receptors control GvHD in a xenograft model 用嵌合抗原受体设计的人 iPSC 衍生 CD4+ Treg 样细胞在异种移植模型中控制 GvHD

IF 23.9 1区医学

Cell stem cell Pub Date : 2024-06-06 DOI: 10.1016/j.stem.2024.05.004

Hisashi Yano, Keiko Koga, Takayuki Sato, Tokuyuki Shinohara, Shoichi Iriguchi, Atsushi Matsuda, Kazuki Nakazono, Maki Shioiri, Yasuyuki Miyake, Yoshiaki Kassai, Hitoshi Kiyoi, Shin Kaneko

{"title":"Human iPSC-derived CD4+ Treg-like cells engineered with chimeric antigen receptors control GvHD in a xenograft model","authors":"Hisashi Yano, Keiko Koga, Takayuki Sato, Tokuyuki Shinohara, Shoichi Iriguchi, Atsushi Matsuda, Kazuki Nakazono, Maki Shioiri, Yasuyuki Miyake, Yoshiaki Kassai, Hitoshi Kiyoi, Shin Kaneko","doi":"10.1016/j.stem.2024.05.004","DOIUrl":"https://doi.org/10.1016/j.stem.2024.05.004","url":null,"abstract":"CD4+ T cells induced from human iPSCs (iCD4+ T cells) offer a therapeutic opportunity for overcoming immune pathologies arising from hematopoietic stem cell transplantation. However, most iCD4+ T cells are conventional helper T cells, which secrete inflammatory cytokines. We induced high-level expression of FOXP3, a master transcription factor of regulatory T cells, in iCD4+ T cells. Human iPSC-derived, FOXP3-induced CD4+ T (iCD4+ Treg-like) cells did not secrete inflammatory cytokines upon activation. Moreover, they showed demethylation of the Treg-specific demethylation region, suggesting successful conversion to immunosuppressive iCD4+ Treg-like cells. We further assessed these iCD4+ Treg-like cells for CAR-mediated immunosuppressive ability. HLA-A2 CAR-transduced iCD4+ Treg-like cells inhibited CD8+ cytotoxic T cell (CTL) division in a mixed lymphocyte reaction assay with A2+ allogeneic CTLs and suppressed xenogeneic graft-versus-host disease (GVHD) in NSG mice treated with A2+ human PBMCs. In most cases, these cells suppressed the xenogeneic GvHD progression as much as natural CD25+CD127− Tregs did.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"34 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141265107","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

Long-term engraftment and maturation of autologous iPSC-derived cardiomyocytes in two rhesus macaques 自体 iPSC 衍生心肌细胞在两只猕猴体内的长期移植和成熟

IF 23.9 1区医学

Cell stem cell Pub Date : 2024-06-05 DOI: 10.1016/j.stem.2024.05.005

Yongshun Lin, Noriko Sato, Sogun Hong, Kenta Nakamura, Elisa A. Ferrante, Zu Xi Yu, Marcus Y. Chen, Daisy S. Nakamura, Xiulan Yang, Randall R. Clevenger, Timothy J. Hunt, Joni L. Taylor, Kenneth R. Jeffries, Karen J. Keeran, Lauren E. Neidig, Atul Mehta, Robin Schwartzbeck, Shiqin Judy Yu, Conor Kelly, Keron Navarengom, Cynthia E. Dunbar

{"title":"Long-term engraftment and maturation of autologous iPSC-derived cardiomyocytes in two rhesus macaques","authors":"Yongshun Lin, Noriko Sato, Sogun Hong, Kenta Nakamura, Elisa A. Ferrante, Zu Xi Yu, Marcus Y. Chen, Daisy S. Nakamura, Xiulan Yang, Randall R. Clevenger, Timothy J. Hunt, Joni L. Taylor, Kenneth R. Jeffries, Karen J. Keeran, Lauren E. Neidig, Atul Mehta, Robin Schwartzbeck, Shiqin Judy Yu, Conor Kelly, Keron Navarengom, Cynthia E. Dunbar","doi":"10.1016/j.stem.2024.05.005","DOIUrl":"https://doi.org/10.1016/j.stem.2024.05.005","url":null,"abstract":"Cellular therapies with cardiomyocytes produced from induced pluripotent stem cells (iPSC-CMs) offer a potential route to cardiac regeneration as a treatment for chronic ischemic heart disease. Here, we report successful long-term engraftment and in vivo maturation of autologous iPSC-CMs in two rhesus macaques with small, subclinical chronic myocardial infarctions, all without immunosuppression. Longitudinal positron emission tomography imaging using the sodium/iodide symporter (NIS) reporter gene revealed stable grafts for over 6 and 12 months, with no teratoma formation. Histological analyses suggested capability of the transplanted iPSC-CMs to mature and integrate with endogenous myocardium, with no sign of immune cell infiltration or rejection. By contrast, allogeneic iPSC-CMs were rejected within 8 weeks of transplantation. This study provides the longest-term safety and maturation data to date in any large animal model, addresses concerns regarding neoantigen immunoreactivity of autologous iPSC therapies, and suggests that autologous iPSC-CMs would similarly engraft and mature in human hearts.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"1 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141252003","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

Naive pluripotent stem cell-based models capture FGF-dependent human hypoblast lineage specification 基于原始多能干细胞的模型捕捉到了依赖于 FGF 的人类下胚层细胞系规范

IF 23.9 1区医学

Cell stem cell Pub Date : 2024-05-31 DOI: 10.1016/j.stem.2024.05.003

Anish Dattani, Elena Corujo-Simon, Arthur Radley, Tiam Heydari, Yasaman Taheriabkenar, Francesca Carlisle, Simeng Lin, Corin Liddle, Jonathan Mill, Peter W. Zandstra, Jennifer Nichols, Ge Guo

{"title":"Naive pluripotent stem cell-based models capture FGF-dependent human hypoblast lineage specification","authors":"Anish Dattani, Elena Corujo-Simon, Arthur Radley, Tiam Heydari, Yasaman Taheriabkenar, Francesca Carlisle, Simeng Lin, Corin Liddle, Jonathan Mill, Peter W. Zandstra, Jennifer Nichols, Ge Guo","doi":"10.1016/j.stem.2024.05.003","DOIUrl":"https://doi.org/10.1016/j.stem.2024.05.003","url":null,"abstract":"The hypoblast is an essential extraembryonic tissue set aside within the inner cell mass in the blastocyst. Research with human embryos is challenging. Thus, stem cell models that reproduce hypoblast differentiation provide valuable alternatives. We show here that human naive pluripotent stem cell (PSC) to hypoblast differentiation proceeds via reversion to a transitional ICM-like state from which the hypoblast emerges in concordance with the trajectory in human blastocysts. We identified a window when fibroblast growth factor (FGF) signaling is critical for hypoblast specification. Revisiting FGF signaling in human embryos revealed that inhibition in the early blastocyst suppresses hypoblast formation. In vitro, the induction of hypoblast is synergistically enhanced by limiting trophectoderm and epiblast fates. This finding revises previous reports and establishes a conservation in lineage specification between mice and humans. Overall, this study demonstrates the utility of human naive PSC-based models in elucidating the mechanistic features of early human embryogenesis.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"41 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141185424","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

SDHAF1 confers metabolic resilience to aging hematopoietic stem cells by promoting mitochondrial ATP production SDHAF1通过促进线粒体ATP的产生，赋予衰老造血干细胞新陈代谢的恢复能力

IF 23.9 1区医学

Cell stem cell Pub Date : 2024-05-20 DOI: 10.1016/j.stem.2024.04.023

Shintaro Watanuki, Hiroshi Kobayashi, Yuki Sugiura, Masamichi Yamamoto, Daiki Karigane, Kohei Shiroshita, Yuriko Sorimachi, Takayuki Morikawa, Shinya Fujita, Kotaro Shide, Miho Haraguchi, Shinpei Tamaki, Takumi Mikawa, Hiroshi Kondoh, Hiroyasu Nakano, Kenta Sumiyama, Go Nagamatsu, Nobuhito Goda, Shinichiro Okamoto, Ayako Nakamura-Ishizu, Keiyo Takubo

{"title":"SDHAF1 confers metabolic resilience to aging hematopoietic stem cells by promoting mitochondrial ATP production","authors":"Shintaro Watanuki, Hiroshi Kobayashi, Yuki Sugiura, Masamichi Yamamoto, Daiki Karigane, Kohei Shiroshita, Yuriko Sorimachi, Takayuki Morikawa, Shinya Fujita, Kotaro Shide, Miho Haraguchi, Shinpei Tamaki, Takumi Mikawa, Hiroshi Kondoh, Hiroyasu Nakano, Kenta Sumiyama, Go Nagamatsu, Nobuhito Goda, Shinichiro Okamoto, Ayako Nakamura-Ishizu, Keiyo Takubo","doi":"10.1016/j.stem.2024.04.023","DOIUrl":"https://doi.org/10.1016/j.stem.2024.04.023","url":null,"abstract":"Aging generally predisposes stem cells to functional decline, impairing tissue homeostasis. Here, we report that hematopoietic stem cells (HSCs) acquire metabolic resilience that promotes cell survival. High-resolution real-time ATP analysis with glucose tracing and metabolic flux analysis revealed that old HSCs reprogram their metabolism to activate the pentose phosphate pathway (PPP), becoming more resistant to oxidative stress and less dependent on glycolytic ATP production at steady state. As a result, old HSCs can survive without glycolysis, adapting to the physiological cytokine environment in bone marrow. Mechanistically, old HSCs enhance mitochondrial complex II metabolism during stress to promote ATP production. Furthermore, increased succinate dehydrogenase assembly factor 1 (SDHAF1) in old HSCs, induced by physiological low-concentration thrombopoietin (TPO) exposure, enables rapid mitochondrial ATP production upon metabolic stress, thereby improving survival. This study provides insight into the acquisition of resilience through metabolic reprogramming in old HSCs and its molecular basis to ameliorate age-related hematopoietic abnormalities.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"15 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2024-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141069209","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