Stem Cell Reports最新文献_第5页

Human microglia-derived proinflammatory cytokines facilitate human retinal ganglion cell development and regeneration. 人类小胶质细胞衍生的促炎细胞因子促进了人类视网膜神经节细胞的发育和再生。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2024-08-13 Epub Date: 2024-07-25 DOI: 10.1016/j.stemcr.2024.06.009

Murali Subramani, Brandon Lambrecht, Iqbal Ahmad

{"title":"Human microglia-derived proinflammatory cytokines facilitate human retinal ganglion cell development and regeneration.","authors":"Murali Subramani, Brandon Lambrecht, Iqbal Ahmad","doi":"10.1016/j.stemcr.2024.06.009","DOIUrl":"10.1016/j.stemcr.2024.06.009","url":null,"abstract":"Microglia (μG), the resident immune cells in the central nervous system, surveil the parenchyma to maintain the structural and functional homeostasis of neurons. Besides, they influence neurogenesis and synaptogenesis through complement-mediated phagocytosis. Emerging evidence suggests that μG may also influence development through proinflammatory cytokines. Here, we examined the premise that tumor necrosis factor alpha (TNF-α) and interleukin-1β (IL-1β), the two most prominent components of the μG secretome, influence retinal development, specifically the morphological and functional differentiation of human retinal ganglion cells (hRGCs). Using controlled generation of hRGCs and human μG (hμG) from pluripotent stem cells, we demonstrate that TNF-α and IL-1β secreted by unchallenged hμG did not influence hRGC generation. However, their presence significantly facilitated neuritogenesis along with the basal function of hRGCs, which involved the recruitment of the AKT/mTOR pathway. We present ex vivo evidence that proinflammatory cytokines may play an important role in the morphological and physiological maturation of hRGCs, which may be recapitulated for regeneration.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11368696/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141767471","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

Feeder-free culture of human pluripotent stem cells drives MDM4-mediated gain of chromosome 1q. 人类多能干细胞的无饲养培养驱动了 MDM4 介导的 1q 染色体增益。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2024-08-13 Epub Date: 2024-07-03 DOI: 10.1016/j.stemcr.2024.06.003

Dylan Stavish, Christopher J Price, Gabriele Gelezauskaite, Haneen Alsehli, Kimberly A Leonhard, Seth M Taapken, Erik M McIntire, Owen Laing, Bethany M James, Jack J Riley, Johanna Zerbib, Duncan Baker, Amy L Harding, Lydia H Jestice, Thomas F Eleveld, Ad J M Gillis, Sanne Hillenius, Leendert H J Looijenga, Paul J Gokhale, Uri Ben-David, Tenneille E Ludwig, Ivana Barbaric

{"title":"Feeder-free culture of human pluripotent stem cells drives MDM4-mediated gain of chromosome 1q.","authors":"Dylan Stavish, Christopher J Price, Gabriele Gelezauskaite, Haneen Alsehli, Kimberly A Leonhard, Seth M Taapken, Erik M McIntire, Owen Laing, Bethany M James, Jack J Riley, Johanna Zerbib, Duncan Baker, Amy L Harding, Lydia H Jestice, Thomas F Eleveld, Ad J M Gillis, Sanne Hillenius, Leendert H J Looijenga, Paul J Gokhale, Uri Ben-David, Tenneille E Ludwig, Ivana Barbaric","doi":"10.1016/j.stemcr.2024.06.003","DOIUrl":"10.1016/j.stemcr.2024.06.003","url":null,"abstract":"Culture-acquired variants in human pluripotent stem cells (hPSCs) hinder their applications in research and clinic. However, the mechanisms that underpin selection of variants remain unclear. Here, through analysis of comprehensive karyotyping datasets from over 23,000 hPSC cultures of more than 1,500 lines, we explored how culture conditions shape variant selection. Strikingly, we identified an association of chromosome 1q gains with feeder-free cultures and noted a rise in its prevalence in recent years, coinciding with increased usage of feeder-free regimens. Competition experiments of multiple isogenic lines with and without a chromosome 1q gain confirmed that 1q variants have an advantage in feeder-free (E8/vitronectin), but not feeder-based, culture. Mechanistically, we show that overexpression of MDM4, located on chromosome 1q, drives variants' advantage in E8/vitronectin by alleviating genome damage-induced apoptosis, which is lower in feeder-based conditions. Our study explains condition-dependent patterns of hPSC aberrations and offers insights into the mechanisms of variant selection.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11368687/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141535314","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

Human microglial cells as a therapeutic target in a neurodevelopmental disease model. 将人类小胶质细胞作为神经发育疾病模型的治疗靶点

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2024-08-13 Epub Date: 2024-07-25 DOI: 10.1016/j.stemcr.2024.06.013

Pinar Mesci, Christopher N LaRock, Jacob J Jeziorski, Hideyuki Nakashima, Natalia Chermont, Adriano Ferrasa, Roberto H Herai, Tomoka Ozaki, Aurian Saleh, Cedric E Snethlage, Sandra Sanchez, Gabriela Goldberg, Cleber A Trujillo, Kinichi Nakashima, Victor Nizet, Alysson R Muotri

{"title":"Human microglial cells as a therapeutic target in a neurodevelopmental disease model.","authors":"Pinar Mesci, Christopher N LaRock, Jacob J Jeziorski, Hideyuki Nakashima, Natalia Chermont, Adriano Ferrasa, Roberto H Herai, Tomoka Ozaki, Aurian Saleh, Cedric E Snethlage, Sandra Sanchez, Gabriela Goldberg, Cleber A Trujillo, Kinichi Nakashima, Victor Nizet, Alysson R Muotri","doi":"10.1016/j.stemcr.2024.06.013","DOIUrl":"10.1016/j.stemcr.2024.06.013","url":null,"abstract":"Although microglia are macrophages of the central nervous system, their involvement is not limited to immune functions. The roles of microglia during development in humans remain poorly understood due to limited access to fetal tissue. To understand how microglia can impact human neurodevelopment, the methyl-CpG binding protein 2 (MECP2) gene was knocked out in human microglia-like cells (MGLs). Disruption of the MECP2 in MGLs led to transcriptional and functional perturbations, including impaired phagocytosis. The co-culture of healthy MGLs with MECP2-knockout (KO) neurons rescued synaptogenesis defects, suggesting a microglial role in synapse formation. A targeted drug screening identified ADH-503, a CD11b agonist, restored phagocytosis and synapse formation in spheroid-MGL co-cultures, significantly improved disease progression, and increased survival in MeCP2-null mice. These results unveil a MECP2-specific regulation of human microglial phagocytosis and identify a novel therapeutic treatment for MECP2-related conditions.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11368698/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141767472","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

Clonal analysis of fetal hematopoietic stem/progenitor cells reveals how post-transplantation capabilities are distributed. 胎儿造血干细胞/祖细胞的克隆分析揭示了移植后能力的分布情况。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2024-08-13 Epub Date: 2024-08-01 DOI: 10.1016/j.stemcr.2024.07.003

Olivia J Stonehouse, Christine Biben, Tom S Weber, Alexandra Garnham, Katie A Fennell, Alison Farley, Antoine F Terreaux, Warren S Alexander, Mark A Dawson, Shalin H Naik, Samir Taoudi

{"title":"Clonal analysis of fetal hematopoietic stem/progenitor cells reveals how post-transplantation capabilities are distributed.","authors":"Olivia J Stonehouse, Christine Biben, Tom S Weber, Alexandra Garnham, Katie A Fennell, Alison Farley, Antoine F Terreaux, Warren S Alexander, Mark A Dawson, Shalin H Naik, Samir Taoudi","doi":"10.1016/j.stemcr.2024.07.003","DOIUrl":"10.1016/j.stemcr.2024.07.003","url":null,"abstract":"It has been proposed that adult hematopoiesis is sustained by multipotent progenitors (MPPs) specified during embryogenesis. Adult-like hematopoietic stem cell (HSC) and MPP immunophenotypes are present in the fetus, but knowledge of their functional capacity is incomplete. We found that fetal MPP populations were functionally similar to adult cells, albeit with some differences in lymphoid output. Clonal assessment revealed that lineage biases arose from differences in patterns of single-/bi-lineage differentiation. Long-term (LT)- and short-term (ST)-HSC populations were distinguished from MPPs according to capacity for clonal multilineage differentiation. We discovered that a large cohort of long-term repopulating units (LT-RUs) resides within the ST-HSC population; a significant portion of these were labeled using Flt3-cre. This finding has two implications: (1) use of the CD150+ LT-HSC immunophenotype alone will significantly underestimate the size and diversity of the LT-RU pool and (2) LT-RUs in the ST-HSC population have the attributes required to persist into adulthood.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11368694/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141879487","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

An in vitro model of acute horizontal basal cell activation reveals gene regulatory networks underlying the nascent activation phase. 急性水平基底细胞活化的体外模型揭示了新生活化阶段的基因调控网络。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2024-08-13 Epub Date: 2024-07-25 DOI: 10.1016/j.stemcr.2024.06.011

Camila M Barrios-Camacho, Matthew J Zunitch, Jonathan D Louie, Woochan Jang, James E Schwob

{"title":"An in vitro model of acute horizontal basal cell activation reveals gene regulatory networks underlying the nascent activation phase.","authors":"Camila M Barrios-Camacho, Matthew J Zunitch, Jonathan D Louie, Woochan Jang, James E Schwob","doi":"10.1016/j.stemcr.2024.06.011","DOIUrl":"10.1016/j.stemcr.2024.06.011","url":null,"abstract":"While horizontal basal cells (HBCs) make minor contributions to olfactory epithelium (OE) regeneration during homeostatic conditions, they possess a potent, latent capacity to activate and subsequently regenerate the OE following severe injury. Activation requires, and is mediated by, the downregulation of the transcription factor (TF) TP63. In this paper, we describe the cellular processes that drive the nascent stages of HBC activation. The compound phorbol 12-myristate 13-acetate (PMA) induces a rapid loss in TP63 protein and rapid enrichment of HOPX and the nuclear translocation of RELA, previously identified as components of HBC activation. Using bulk RNA sequencing (RNA-seq), we find that PMA-treated HBCs pass through various stages of activation identifiable by transcriptional regulatory signatures that mimic stages identified in vivo. These temporal stages are associated with varying degrees of engraftment and differentiation potential in transplantation assays. Together, these data show that our in vitro HBC activation system models physiologically relevant features of in vivo HBC activation and identifies new candidates for mechanistic testing.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11368683/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141767470","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

Retinal cells derived from patients with DRAM2-dependent CORD21 dystrophy exhibit key lysosomal enzyme deficiency and lysosomal content accumulation. DRAM2依赖性CORD21营养不良症患者的视网膜细胞表现出关键溶酶体酶缺乏和溶酶体内容物积累。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2024-08-13 Epub Date: 2024-07-03 DOI: 10.1016/j.stemcr.2024.06.002

Rozaliya Tsikandelova, Eldo Galo, Edvinas Cerniauskas, Dean Hallam, Maria Georgiou, Rodrigo Cerna-Chavez, Robert Atkinson, Pavel Palmowski, Florence Burté, Tracey Davies, David H Steel, Martin McKibbin, Jacquelyn Bond, Jennifer Haggarty, Phil Whitfield, Viktor Korolchuk, Lyle Armstrong, Chunbo Yang, Birthe Dorgau, Marzena Kurzawa-Akanbi, Majlinda Lako

{"title":"Retinal cells derived from patients with DRAM2-dependent CORD21 dystrophy exhibit key lysosomal enzyme deficiency and lysosomal content accumulation.","authors":"Rozaliya Tsikandelova, Eldo Galo, Edvinas Cerniauskas, Dean Hallam, Maria Georgiou, Rodrigo Cerna-Chavez, Robert Atkinson, Pavel Palmowski, Florence Burté, Tracey Davies, David H Steel, Martin McKibbin, Jacquelyn Bond, Jennifer Haggarty, Phil Whitfield, Viktor Korolchuk, Lyle Armstrong, Chunbo Yang, Birthe Dorgau, Marzena Kurzawa-Akanbi, Majlinda Lako","doi":"10.1016/j.stemcr.2024.06.002","DOIUrl":"10.1016/j.stemcr.2024.06.002","url":null,"abstract":"Biallelic mutations in DRAM2 lead to an autosomal recessive cone-rod dystrophy known as CORD21, which typically presents between the third and sixth decades of life. Although DRAM2 localizes to the lysosomes of photoreceptor and retinal pigment epithelium (RPE) cells, its specific role in retinal degeneration has not been fully elucidated. In this study, we generated and characterized retinal organoids (ROs) and RPE cells from induced pluripotent stem cells (iPSCs) derived from two CORD21 patients. Our investigation revealed that CORD21-ROs and RPE cells exhibit abnormalities in lipid metabolism, defects in autophagic flux, accumulation of aberrant lysosomal content, and reduced lysosomal enzyme activity. We identified potential interactions of DRAM2 with vesicular trafficking proteins, suggesting its involvement in this cellular process. These findings collectively suggest that DRAM2 plays a crucial role in maintaining the integrity of photoreceptors and RPE cells by regulating lysosomal function, autophagy, and potentially vesicular trafficking.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11368688/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141535315","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

Skeletal muscle-on-a-chip in microgravity as a platform for regeneration modeling and drug screening. 微重力条件下的芯片骨骼肌作为再生建模和药物筛选平台。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2024-08-13 Epub Date: 2024-07-25 DOI: 10.1016/j.stemcr.2024.06.010

Soochi Kim, Bugra Ayan, Mahdis Shayan, Thomas A Rando, Ngan F Huang

{"title":"Skeletal muscle-on-a-chip in microgravity as a platform for regeneration modeling and drug screening.","authors":"Soochi Kim, Bugra Ayan, Mahdis Shayan, Thomas A Rando, Ngan F Huang","doi":"10.1016/j.stemcr.2024.06.010","DOIUrl":"10.1016/j.stemcr.2024.06.010","url":null,"abstract":"Microgravity has been shown to lead to both muscle atrophy and impaired muscle regeneration. The purpose was to study the efficacy of microgravity to model impaired muscle regeneration in an engineered muscle platform and then to demonstrate the feasibility of performing drug screening in this model. Engineered human muscle was launched to the International Space Station National Laboratory, where the effect of microgravity exposure for 7 days was examined by transcriptomics and proteomics approaches. Gene set enrichment analysis of engineered muscle cultured in microgravity, compared to normal gravity conditions, highlighted a metabolic shift toward lipid and fatty acid metabolism, along with increased apoptotic gene expression. The addition of pro-regenerative drugs, insulin-like growth factor-1 (IGF-1) and a 15-hydroxyprostaglandin dehydrogenase inhibitor (15-PGDH-i), partially inhibited the effects of microgravity. In summary, microgravity mimics aspects of impaired myogenesis, and the addition of these drugs could partially inhibit the effects induced by microgravity.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11368695/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141767474","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 dual-color PAX7 and MYF5 in vivo reporter to investigate muscle stem cell heterogeneity in regeneration and aging. 双色 PAX7 和 MYF5 体内报告器，用于研究再生和衰老过程中肌肉干细胞的异质性。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2024-07-09 Epub Date: 2024-06-13 DOI: 10.1016/j.stemcr.2024.05.005

Sara Ancel, Joris Michaud, Federico Sizzano, Loic Tauzin, Manuel Oliveira, Eugenia Migliavacca, Svenja C Schüler, Sruthi Raja, Gabriele Dammone, Sonia Karaz, José L Sánchez-García, Sylviane Metairon, Guillaume Jacot, C Florian Bentzinger, Jérôme N Feige, Pascal Stuelsatz

{"title":"A dual-color PAX7 and MYF5 in vivo reporter to investigate muscle stem cell heterogeneity in regeneration and aging.","authors":"Sara Ancel, Joris Michaud, Federico Sizzano, Loic Tauzin, Manuel Oliveira, Eugenia Migliavacca, Svenja C Schüler, Sruthi Raja, Gabriele Dammone, Sonia Karaz, José L Sánchez-García, Sylviane Metairon, Guillaume Jacot, C Florian Bentzinger, Jérôme N Feige, Pascal Stuelsatz","doi":"10.1016/j.stemcr.2024.05.005","DOIUrl":"10.1016/j.stemcr.2024.05.005","url":null,"abstract":"Increasing evidence suggests that the muscle stem cell (MuSC) pool is heterogeneous. In particular, a rare subset of PAX7-positive MuSCs that has never expressed the myogenic regulatory factor MYF5 displays unique self-renewal and engraftment characteristics. However, the scarcity and limited availability of protein markers make the characterization of these cells challenging. Here, we describe the generation of StemRep reporter mice enabling the monitoring of PAX7 and MYF5 proteins based on equimolar levels of dual nuclear fluorescence. High levels of PAX7 protein and low levels of MYF5 delineate a deeply quiescent MuSC subpopulation with an increased capacity for asymmetric division and distinct dynamics of activation, proliferation, and commitment. Aging primarily reduces the MYF5Low MuSCs and skews the stem cell pool toward MYF5High cells with lower quiescence and self-renewal potential. Altogether, we establish the StemRep model as a versatile tool to study MuSC heterogeneity and broaden our understanding of mechanisms regulating MuSC quiescence and self-renewal in homeostatic, regenerating, and aged muscles.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11252486/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141321676","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

Anticipating in vitro gametogenesis: Hopes and concerns for IVG among diverse stakeholders. 预期体外配子生成：不同利益相关者对体外配子生成的希望和担忧。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2024-07-09 Epub Date: 2024-06-06 DOI: 10.1016/j.stemcr.2024.05.002

Anne Le Goff, Robbin Jeffries Hein, Ariel N Hart, Isaias Roberson, Hannah L Landecker

{"title":"Anticipating in vitro gametogenesis: Hopes and concerns for IVG among diverse stakeholders.","authors":"Anne Le Goff, Robbin Jeffries Hein, Ariel N Hart, Isaias Roberson, Hannah L Landecker","doi":"10.1016/j.stemcr.2024.05.002","DOIUrl":"10.1016/j.stemcr.2024.05.002","url":null,"abstract":"In vitro gametogenesis (IVG), the reconstitution of germ cell development in vitro, is an emerging stem cell-based technology with profound implications for reproductive science. Despite researchers' long-term goals for future clinical applications, little is currently known about the views of IVG held by the stakeholders potentially most affected by its introduction in humans. We conducted focus groups and interviews with 80 individuals with lived experience of infertility and/or LGBTQ+ family formation in the US, two intersecting groups of potential IVG users. Respondents expressed hope that IVG would lead to higher reproductive success than current assisted reproductive technology (ART), alleviate suffering associated with ART use, and promote greater social inclusion, while expressing concerns predominantly framed in terms of equity and safety. These findings underscore the importance of sustained engagement with stakeholders with relevant experience to anticipate the implications of IVG for research and clinical translation.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11252480/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141288691","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

Self-assembling 3D vessel-on-chip model with hiPSC-derived astrocytes. 利用源自 hiPSC 的星形胶质细胞自组装三维片上血管模型。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2024-07-09 Epub Date: 2024-06-13 DOI: 10.1016/j.stemcr.2024.05.006

Dennis M Nahon, Marc Vila Cuenca, Francijna E van den Hil, Michel Hu, Tessa de Korte, Jean-Philippe Frimat, Arn M J M van den Maagdenberg, Christine L Mummery, Valeria V Orlova

{"title":"Self-assembling 3D vessel-on-chip model with hiPSC-derived astrocytes.","authors":"Dennis M Nahon, Marc Vila Cuenca, Francijna E van den Hil, Michel Hu, Tessa de Korte, Jean-Philippe Frimat, Arn M J M van den Maagdenberg, Christine L Mummery, Valeria V Orlova","doi":"10.1016/j.stemcr.2024.05.006","DOIUrl":"10.1016/j.stemcr.2024.05.006","url":null,"abstract":"Functionality of the blood-brain barrier (BBB) relies on the interaction between endothelial cells (ECs), pericytes, and astrocytes to regulate molecule transport within the central nervous system. Most experimental models for the BBB rely on freshly isolated primary brain cells. Here, we explored human induced pluripotent stem cells (hiPSCs) as a cellular source for astrocytes in a 3D vessel-on-chip (VoC) model. Self-organized microvascular networks were formed by combining hiPSC-derived ECs, human brain vascular pericytes, and hiPSC-derived astrocytes within a fibrin hydrogel. The hiPSC-ECs and pericytes showed close interactions, but, somewhat unexpectedly, addition of astrocytes disrupted microvascular network formation. However, continuous fluid perfusion or activation of cyclic AMP (cAMP) signaling rescued the vascular organization and decreased vascular permeability. Nevertheless, astrocytes did not affect the expression of proteins related to junction formation, transport, or extracellular matrix, indicating that, despite other claims, hiPSC-derived ECs do not entirely acquire a BBB-like identity in the 3D VoC model.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11252484/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141321678","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