Stem Cell ReportsPub Date : 2024-04-01DOI: 10.1016/j.stemcr.2024.03.007
Nirupam Biswas, Amber Bahr, Jennifer Howard, Jesse L. Bonin, Rachel Grazda, Katherine C. MacNamara
{"title":"Survivors of polymicrobial sepsis are refractory to G-CSF-induced emergency myelopoiesis and hematopoietic stem and progenitor cell mobilization.","authors":"Nirupam Biswas, Amber Bahr, Jennifer Howard, Jesse L. Bonin, Rachel Grazda, Katherine C. MacNamara","doi":"10.1016/j.stemcr.2024.03.007","DOIUrl":"https://doi.org/10.1016/j.stemcr.2024.03.007","url":null,"abstract":"","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140787280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Stem Cell ReportsPub Date : 2024-04-01DOI: 10.1016/j.stemcr.2024.03.009
David Pamies, Jason Ekert, M. Zurich, Olivier Frey, Sophie Werner, Monica Piergiovanni, Benjamin S. Freedman, Adrian Kee Keong Teo, Hendrik Erfurth, Darwin R. Reyes, Peter Loskill, Pelin Candarlioglu, Laura Suter-Dick, Shan Wang, Thomas Hartung, Sandra Coecke, Glyn Stacey, Beren Atac Wagegg, Eva-Maria Dehne, Francesca Pistollato, Marcel Leist
{"title":"Recommendations on fit-for-purpose criteria to establish quality management for microphysiological systems and for monitoring their reproducibility","authors":"David Pamies, Jason Ekert, M. Zurich, Olivier Frey, Sophie Werner, Monica Piergiovanni, Benjamin S. Freedman, Adrian Kee Keong Teo, Hendrik Erfurth, Darwin R. Reyes, Peter Loskill, Pelin Candarlioglu, Laura Suter-Dick, Shan Wang, Thomas Hartung, Sandra Coecke, Glyn Stacey, Beren Atac Wagegg, Eva-Maria Dehne, Francesca Pistollato, Marcel Leist","doi":"10.1016/j.stemcr.2024.03.009","DOIUrl":"https://doi.org/10.1016/j.stemcr.2024.03.009","url":null,"abstract":"","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140783446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Human-induced pluripotent stem cell-derived neural stem/progenitor cell ex vivo gene therapy with synaptic organizer CPTX for spinal cord injury.","authors":"Yusuke Saijo, Narihito Nagoshi, Momotaro Kawai, Takahiro Kitagawa, Yu Suematsu, Masahiro Ozaki, Munehisa Shinozaki, Jun Kohyama, Shinsuke Shibata, Kosei Takeuchi, Masaya Nakamura, Michisuke Yuzaki, Hideyuki Okano","doi":"10.1016/j.stemcr.2024.01.007","DOIUrl":"10.1016/j.stemcr.2024.01.007","url":null,"abstract":"<p><p>The transplantation of neural stem/progenitor cells (NS/PCs) derived from human induced pluripotent stem cells (hiPSCs) has shown promise in spinal cord injury (SCI) model animals. Establishing a functional synaptic connection between the transplanted and host neurons is crucial for motor function recovery. To boost therapeutic outcomes, we developed an ex vivo gene therapy aimed at promoting synapse formation by expressing the synthetic excitatory synapse organizer CPTX in hiPSC-NS/PCs. Using an immunocompromised transgenic rat model of SCI, we evaluated the effects of transplanting CPTX-expressing hiPSC-NS/PCs using histological and functional analyses. Our findings revealed a significant increase in excitatory synapse formation at the transplantation site. Retrograde monosynaptic tracing indicated extensive integration of transplanted neurons into the surrounding neuronal tracts facilitated by CPTX. Consequently, locomotion and spinal cord conduction significantly improved. Thus, ex vivo gene therapy targeting synapse formation holds promise for future clinical applications and offers potential benefits to individuals with SCI.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10937157/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139747407","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}
Stem Cell ReportsPub Date : 2024-03-12Epub Date: 2024-02-29DOI: 10.1016/j.stemcr.2024.02.001
Yuansong Liao, Fanchen Kang, Jingfei Xiong, Kun Xie, Mingxu Li, Ling Yu, Yuqing Wang, Hanyi Chen, Guogen Ye, Yike Yin, Weihua Guo, Haoyang Cai, Qing Zhu, Zhonghan Li
{"title":"MSX1<sup>+</sup>PDGFRA<sup>low</sup> limb mesenchyme-like cells as an efficient stem cell source for human cartilage regeneration.","authors":"Yuansong Liao, Fanchen Kang, Jingfei Xiong, Kun Xie, Mingxu Li, Ling Yu, Yuqing Wang, Hanyi Chen, Guogen Ye, Yike Yin, Weihua Guo, Haoyang Cai, Qing Zhu, Zhonghan Li","doi":"10.1016/j.stemcr.2024.02.001","DOIUrl":"10.1016/j.stemcr.2024.02.001","url":null,"abstract":"<p><p>Degenerative bone disorders have a significant impact on global health, and regeneration of articular cartilage remains a challenge. Existing cell therapies using mesenchymal stromal cells (MSCs) have shown limited efficacy, highlighting the necessity for alternative stem cell sources. Here, we have identified and characterized MSX1<sup>+</sup> mesenchymal progenitor cells in the developing limb bud with remarkable osteochondral-regenerative and microenvironment-adaptive capabilities. Single-cell sequencing further revealed the presence of two major cell compositions within the MSX1<sup>+</sup> cells, where a distinct PDGFRA<sup>low</sup> subset retained the strongest osteochondral competency and could efficiently regenerate articular cartilage in vivo. Furthermore, a strategy was developed to generate MSX1<sup>+</sup>PDGFRA<sup>low</sup> limb mesenchyme-like (LML) cells from human pluripotent stem cells that closely resembled their mouse counterparts, which were bipotential in vitro and could directly regenerate damaged cartilage in a mouse injury model. Together, our results indicated that MSX1<sup>+</sup>PDGFRA<sup>low</sup> LML cells might be a prominent stem cell source for human cartilage regeneration.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10937155/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140013316","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}
Stem Cell ReportsPub Date : 2024-03-12Epub Date: 2024-02-15DOI: 10.1016/j.stemcr.2024.01.008
Katja Baur, Carmen Carrillo-García, Şeydanur Şan, Manja von Hahn, Jens Strelau, Gabriele Hölzl-Wenig, Claudia Mandl, Francesca Ciccolini
{"title":"Growth/differentiation factor 15 controls ependymal and stem cell number in the V-SVZ.","authors":"Katja Baur, Carmen Carrillo-García, Şeydanur Şan, Manja von Hahn, Jens Strelau, Gabriele Hölzl-Wenig, Claudia Mandl, Francesca Ciccolini","doi":"10.1016/j.stemcr.2024.01.008","DOIUrl":"10.1016/j.stemcr.2024.01.008","url":null,"abstract":"<p><p>The expression of growth/differentiation factor (GDF) 15 increases in the ganglionic eminence (GE) late in neural development, especially in neural stem cells (NSCs). However, GDF15 function in this region remains unknown. We report that GDF15 receptor is expressed apically in the GE and that GDF15 ablation promotes proliferation and cell division in the embryonic GE and in the adult ventricular-subventricular zone (V-SVZ). This causes a transient generation of additional neuronal progenitors, compensated by cell death, and a lasting increase in the number of ependymal cells and apical NSCs. Finally, both GDF15 receptor and the epidermal growth factor receptor (EGFR) were expressed in progenitors and mutation of GDF15 affected EGFR signaling. However, only exposure to exogenous GDF15, but not to EGF, normalized proliferation and the number of apical progenitors. Thus, GDF15 regulates proliferation of apical progenitors in the GE, thereby affecting the number of ependymal cells and NSCs.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10937156/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139747406","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}
Stem Cell ReportsPub Date : 2024-03-12Epub Date: 2024-02-08DOI: 10.1016/j.stemcr.2024.01.002
Jacob A Klickstein, Michelle A Johnson, Pantelis Antonoudiou, Jamie Maguire, Joao A Paulo, Steve P Gygi, Chris Weihl, Malavika Raman
{"title":"ALS-related p97 R155H mutation disrupts lysophagy in iPSC-derived motor neurons.","authors":"Jacob A Klickstein, Michelle A Johnson, Pantelis Antonoudiou, Jamie Maguire, Joao A Paulo, Steve P Gygi, Chris Weihl, Malavika Raman","doi":"10.1016/j.stemcr.2024.01.002","DOIUrl":"10.1016/j.stemcr.2024.01.002","url":null,"abstract":"<p><p>Mutations in the AAA+ ATPase p97 cause multisystem proteinopathy 1, which includes amyotrophic lateral sclerosis; however, the pathogenic mechanisms that contribute to motor neuron loss remain obscure. Here, we use two induced pluripotent stem cell models differentiated into spinal motor neurons to investigate how p97 mutations perturb the motor neuron proteome. Using quantitative proteomics, we find that motor neurons harboring the p97 R155H mutation have deficits in the selective autophagy of lysosomes (lysophagy). p97 R155H motor neurons are unable to clear damaged lysosomes and have reduced viability. Lysosomes in mutant motor neurons have increased pH compared with wild-type cells. The clearance of damaged lysosomes involves UBXD1-p97 interaction, which is disrupted in mutant motor neurons. Finally, inhibition of the ATPase activity of p97 using the inhibitor CB-5083 rescues lysophagy defects in mutant motor neurons. These results add to the evidence that endo-lysosomal dysfunction is a key aspect of disease pathogenesis in p97-related disorders.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10937112/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139713094","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}
Stem Cell ReportsPub Date : 2024-03-12Epub Date: 2024-02-08DOI: 10.1016/j.stemcr.2024.01.003
Aleksandra Kostina, Yonatan R Lewis-Israeli, Mishref Abdelhamid, Mitchell A Gabalski, Artem Kiselev, Brett D Volmert, Haley Lankerd, Amanda R Huang, Aaron H Wasserman, Todd Lydic, Christina Chan, Sangbum Park, Isoken Olomu, Aitor Aguirre
{"title":"ER stress and lipid imbalance drive diabetic embryonic cardiomyopathy in an organoid model of human heart development.","authors":"Aleksandra Kostina, Yonatan R Lewis-Israeli, Mishref Abdelhamid, Mitchell A Gabalski, Artem Kiselev, Brett D Volmert, Haley Lankerd, Amanda R Huang, Aaron H Wasserman, Todd Lydic, Christina Chan, Sangbum Park, Isoken Olomu, Aitor Aguirre","doi":"10.1016/j.stemcr.2024.01.003","DOIUrl":"10.1016/j.stemcr.2024.01.003","url":null,"abstract":"<p><p>Congenital heart defects are the most prevalent human birth defects, and their incidence is exacerbated by maternal health conditions, such as diabetes during the first trimester (pregestational diabetes). Our understanding of the pathology of these disorders is hindered by a lack of human models and the inaccessibility of embryonic tissue. Using an advanced human heart organoid system, we simulated embryonic heart development under pregestational diabetes-like conditions. These organoids developed pathophysiological features observed in mouse and human studies before, including ROS-mediated stress and cardiomyocyte hypertrophy. scRNA-seq revealed cardiac cell-type-specific dysfunction affecting epicardial and cardiomyocyte populations and alterations in the endoplasmic reticulum and very-long-chain fatty acid lipid metabolism. Imaging and lipidomics confirmed these findings and showed that dyslipidemia was linked to fatty acid desaturase 2 mRNA decay dependent on IRE1-RIDD signaling. Targeting IRE1 or restoring lipid levels partially reversed the effects of pregestational diabetes, offering potential preventive and therapeutic strategies in humans.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10937107/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139713095","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}
Stem Cell ReportsPub Date : 2024-03-12Epub Date: 2024-02-08DOI: 10.1016/j.stemcr.2024.01.005
Ching Tzu Yu, Sangeetha Kandoi, Ramesh Periasamy, L Vinod K Reddy, Hannah M Follett, Phyllis Summerfelt, Cassandra Martinez, Chloe Guillaume, Owen Bowie, Thomas B Connor, Daniel M Lipinski, Kenneth P Allen, Dana K Merriman, Joseph Carroll, Deepak A Lamba
{"title":"Human iPSC-derived photoreceptor transplantation in the cone dominant 13-lined ground squirrel.","authors":"Ching Tzu Yu, Sangeetha Kandoi, Ramesh Periasamy, L Vinod K Reddy, Hannah M Follett, Phyllis Summerfelt, Cassandra Martinez, Chloe Guillaume, Owen Bowie, Thomas B Connor, Daniel M Lipinski, Kenneth P Allen, Dana K Merriman, Joseph Carroll, Deepak A Lamba","doi":"10.1016/j.stemcr.2024.01.005","DOIUrl":"10.1016/j.stemcr.2024.01.005","url":null,"abstract":"<p><p>Several retinal degenerations affect the human central retina, which is primarily comprised of cones and is essential for high acuity and color vision. Transplanting cone photoreceptors is a promising strategy to replace degenerated cones in this region. Although this approach has been investigated in a handful of animal models, commonly used rodent models lack a cone-rich region and larger models can be expensive and inaccessible, impeding the translation of therapies. Here, we transplanted dissociated GFP-expressing photoreceptors from retinal organoids differentiated from human induced pluripotent stem cells into the subretinal space of damaged and undamaged cone-dominant 13-lined ground squirrel eyes. Transplanted cell survival was documented via noninvasive high-resolution imaging and immunohistochemistry to confirm the presence of human donor photoreceptors for up to 4 months posttransplantation. These results demonstrate the utility of a cone-dominant rodent model for advancing the clinical translation of cell replacement therapies.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10937153/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139713097","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}
Stem Cell ReportsPub Date : 2024-03-12Epub Date: 2024-02-08DOI: 10.1016/j.stemcr.2024.01.004
Juan A Perez-Bermejo, Samuel J Reisman, Joyce Ma, Dana Carrison-Stone, Chris Cerrito, Alexandre J S Ribeiro, Bruce R Conklin, Kristina Yu
{"title":"Give heart cells a beat: An interactive museum exhibit that synchronizes stem cell-derived cardiomyocytes to visitors' heartbeat.","authors":"Juan A Perez-Bermejo, Samuel J Reisman, Joyce Ma, Dana Carrison-Stone, Chris Cerrito, Alexandre J S Ribeiro, Bruce R Conklin, Kristina Yu","doi":"10.1016/j.stemcr.2024.01.004","DOIUrl":"10.1016/j.stemcr.2024.01.004","url":null,"abstract":"<p><p>Science museums play an important role in science education, engaging the public with science concepts and building support for scientific research. Here, we describe Give Heart Cells a Beat, an interactive exhibit that lets museum visitors synchronize the beating of live stem cell-derived cardiomyocytes to their own heart rate in real time. The beat rate of cells accurately matched the beat rate of visitors and responded dynamically to changes such as exercise. Visitor evaluation revealed that engagement with the specimen prompted curiosity in heart biology and stem cells. Give Heart Cells a Beat is the product of a close collaboration between a museum and an academic research laboratory, and to our knowledge, it is the first interactive exhibit to use live human heart cells. We hope this exhibit serves as an example for the implementation of stem cell technology in informal science education and inspires future relationships between academia and public science venues.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10937149/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139713096","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}
Stem Cell ReportsPub Date : 2024-03-12Epub Date: 2024-02-08DOI: 10.1016/j.stemcr.2024.01.006
Imre F Schene, Arif I Ardisasmita, Sabine A Fuchs
{"title":"Misidentification of neural cell identity in liver-derived organoid systems.","authors":"Imre F Schene, Arif I Ardisasmita, Sabine A Fuchs","doi":"10.1016/j.stemcr.2024.01.006","DOIUrl":"10.1016/j.stemcr.2024.01.006","url":null,"abstract":"","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10937148/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139713098","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}