Abraham P Lee, Mohammad Aghaamoo, Tayloria N G Adams, Lisa A Flanagan
{"title":"It's Electric: When Technology Gives a Boost to Stem Cell Science.","authors":"Abraham P Lee, Mohammad Aghaamoo, Tayloria N G Adams, Lisa A Flanagan","doi":"10.1007/s40778-018-0124-x","DOIUrl":"https://doi.org/10.1007/s40778-018-0124-x","url":null,"abstract":"<p><strong>Purpose of review: </strong>Advanced technologies can aid discoveries in stem cell science in surprising ways. The application of electrokinetic techniques, which use electric fields to interrogate or separate cells, to the study of stem cells has yielded important insights into stem cell function. These techniques probe inherent cell properties, obviating the need for cell-type specific labels.</p><p><strong>Recent findings: </strong>Analysis of a variety of stem cell types including hematopoietic, mesenchymal and adipose-derived, neural, and pluripotent stem cells by electrokinetic techniques has revealed fate-specific signatures of cells. Distinct inherent cell properties are sufficient for their label-free enrichment without causing cell damage or toxicity.</p><p><strong>Summary: </strong>The successful application of label-free techniques to the analysis and sorting of stem cells open new avenues for exploring the basic biology of stem cells and optimizing their use in regenerative medicine applications.</p>","PeriodicalId":37444,"journal":{"name":"Current Stem Cell Reports","volume":" ","pages":"116-126"},"PeriodicalIF":1.4,"publicationDate":"2018-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s40778-018-0124-x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40654408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xinxin Huang, Thao Trinh, Arafat Aljoufi, Hal E Broxmeyer
{"title":"Hypoxia Signaling Pathway in Stem Cell Regulation: Good and Evil.","authors":"Xinxin Huang, Thao Trinh, Arafat Aljoufi, Hal E Broxmeyer","doi":"10.1007/s40778-018-0127-7","DOIUrl":"https://doi.org/10.1007/s40778-018-0127-7","url":null,"abstract":"<p><strong>Purpose of review: </strong>This review summarizes the role of hypoxia and hypoxia-inducible factors (HIFs) in the regulation of stem cell biology, specifically focusing on maintenance, differentiation, and stress responses in the context of several stem cell systems. Stem cells for different lineages/tissues reside in distinct niches, and are exposed to diverse oxygen concentrations. Recent studies have revealed the importance of the hypoxia signaling pathway for stem cell functions.</p><p><strong>Recent findings: </strong>Hypoxia and HIFs contribute to maintenance of embryonic stem cells, generation of induced pluripotent stem cells, functionality of hematopoietic stem cells, and survival of leukemia stem cells. Harvest and collection of mouse bone marrow and human cord blood cells in ambient air results in fewer hematopoietic stem cells recovered due to the phenomenon of Extra PHysiologic Oxygen Shock/Stress (EPHOSS).</p><p><strong>Summary: </strong>Oxygen is an important factor in the stem cell microenvironment. Hypoxia signaling and HIFs play important roles in modeling cellular metabolism in both stem cells and niches to regulate stem cell biology, and represent an additional dimension that allows stem cells to maintain an undifferentiated status and multilineage differentiation potential.</p>","PeriodicalId":37444,"journal":{"name":"Current Stem Cell Reports","volume":"4 2","pages":"149-157"},"PeriodicalIF":1.4,"publicationDate":"2018-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s40778-018-0127-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37397569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Personalizing Cancer Treatments Empirically in the Laboratory: Patient-Specific Tumor Organoids for Optimizing Precision Medicine","authors":"Andrea Mazzocchi, K. Votanopoulos, A. Skardal","doi":"10.1007/s40778-018-0122-z","DOIUrl":"https://doi.org/10.1007/s40778-018-0122-z","url":null,"abstract":"","PeriodicalId":37444,"journal":{"name":"Current Stem Cell Reports","volume":"4 1","pages":"97 - 104"},"PeriodicalIF":1.4,"publicationDate":"2018-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s40778-018-0122-z","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"52901872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Epigenetic and Epitranscriptomic Factors Make a Mark on Hematopoietic Stem Cell Development.","authors":"Dionna M Kasper, Stefania Nicoli","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose of the review: </strong>Blood specification is a highly dynamic process, whereby committed hemogenic endothelial cells (ECs) progressively transdifferentiate into multipotent, self-renewing hematopoietic stem cells (HSCs). Massive changes in gene expression must occur to switch cell identity, however the factors that mediate such an effect were a mystery until recently. This review summarizes the higher-order mechanisms involved in endothelial to hematopoietic reprogramming identified thus far.</p><p><strong>Recent findings: </strong>Accumulating evidence from mouse and zebrafish studies reveal that numerous chromatin-modifying (epigenetic) and RNA-modifying (epitranscriptomic) factors are required for the formation of HSCs from hemogenic endothelium. These genes function throughout the endothelial-hematopoietic transition, suggesting a dynamic interplay between 'epi'-machineries.</p><p><strong>Summary: </strong>Epigenetic and epitranscriptomic regulation are key mechanisms for reshaping global EC gene expression patterns to those that support HSC production. Future studies that capture modification dynamics should bring us closer to a complete understanding of how HSCs transition from hemogenic endothelium at the molecular level.</p>","PeriodicalId":37444,"journal":{"name":"Current Stem Cell Reports","volume":"4 1","pages":"22-32"},"PeriodicalIF":1.4,"publicationDate":"2018-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5999335/pdf/nihms939941.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10441003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Hurdles Associated with the Translational Use of Genetically Modified Cells.","authors":"Sunil S Raikar, H Trent Spencer","doi":"10.1007/s40778-018-0115-y","DOIUrl":"https://doi.org/10.1007/s40778-018-0115-y","url":null,"abstract":"<p><strong>Purpose of review: </strong>Recent advancements in the use of genetically modified hematopoietic stem cells (HSCs) and the emergent use of chimeric antigen receptor (CAR) T-cell immunotherapy has highlighted issues associated with the use of genetically engineered cellular products. This review explores some of the challenges linked with translating the use of genetically modified cells.</p><p><strong>Recent findings: </strong>The use of genetically modified HSCs for ADA-SCID now has European approval and the U.S. Food and Drug Administration recently approved the use of CAR-T cells for relapsed/refractory B-cell acute lymphoblastic leukemia. Current good manufacturing processes have now been developed for the collection, expansion, storage, modification, and administration of genetically modified cells.</p><p><strong>Summary: </strong>Genetically engineered cells can be used for several therapeutic purposes. However, significant challenges remain in making these cellular therapeutics readily available. A better understanding of this technology along with improvements in the manufacturing process is allowing the translation process to become more standardized.</p>","PeriodicalId":37444,"journal":{"name":"Current Stem Cell Reports","volume":" ","pages":"39-45"},"PeriodicalIF":1.4,"publicationDate":"2018-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s40778-018-0115-y","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38768115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Correction to: The Role of Intestinal Stem Cells in Epithelial Regeneration Following Radiation-Induced Gut Injury","authors":"Chang-Kyung Kim, V. Yang, A. Bialkowska","doi":"10.1007/s40778-018-0121-0","DOIUrl":"https://doi.org/10.1007/s40778-018-0121-0","url":null,"abstract":"","PeriodicalId":37444,"journal":{"name":"Current Stem Cell Reports","volume":"4 1","pages":"95 - 95"},"PeriodicalIF":1.4,"publicationDate":"2018-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s40778-018-0121-0","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43328560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Development of the Artificial Womb","authors":"E. Partridge, M. Davey, A. Flake","doi":"10.1007/s40778-018-0120-1","DOIUrl":"https://doi.org/10.1007/s40778-018-0120-1","url":null,"abstract":"","PeriodicalId":37444,"journal":{"name":"Current Stem Cell Reports","volume":"4 1","pages":"69 - 73"},"PeriodicalIF":1.4,"publicationDate":"2018-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s40778-018-0120-1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"52901804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Brian Nankervis, Mark Jones, Boah Vang, R Brent Rice, Claire Coeshott, Jim Beltzer
{"title":"Optimizing T Cell Expansion in a Hollow-Fiber Bioreactor.","authors":"Brian Nankervis, Mark Jones, Boah Vang, R Brent Rice, Claire Coeshott, Jim Beltzer","doi":"10.1007/s40778-018-0116-x","DOIUrl":"https://doi.org/10.1007/s40778-018-0116-x","url":null,"abstract":"<p><strong>Purpose of review: </strong>Recent developments in regenerative medicine have precipitated the need to expand gene-modified human T cells to numbers that exceed the capacity of well-plate-based, and flask-based processes. This review discusses the changes in process development that are needed to meet the cell expansion requirements by utilizing <i>hollow-fiber bioreactors</i>. Maintenance of cell proliferation over long periods can become limited by unfilled demands for nutrients and oxygen and by the accumulation of waste products in the local environment.</p><p><strong>Recent findings: </strong>Perfusion feeding, improved gas exchange, and the efficient removal of lactate can increase the yield of T cells from an average of 10.8E +09 to more than 28E +09 in only 10 days.</p><p><strong>Summary: </strong>Aggressively feeding cells and actively keeping cells in the bioreactor improves gas exchange and metabolite management over semi-static methods. The ability to remove the environmental constraints that can limit cell expansion by using a two-chamber hollow-fiber bioreactor will be discussed.</p>","PeriodicalId":37444,"journal":{"name":"Current Stem Cell Reports","volume":" ","pages":"46-51"},"PeriodicalIF":1.4,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s40778-018-0116-x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35961274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"How and Why to Replace the 14-Day Rule.","authors":"Sarah Chan","doi":"10.1007/s40778-018-0135-7","DOIUrl":"https://doi.org/10.1007/s40778-018-0135-7","url":null,"abstract":"<p><strong>Purpose of review: </strong>The '14-day rule', which limits research on human embryos to the first 14 days after fertilisation, has long been a pillar of regulation in this contested area. Recently, advances in developmental biology have led to calls to rethink the rule and its application. In this paper, I address the question of whether the 14-day rule should be replaced and, if so, how.</p><p><strong>Recent findings: </strong>The two lines of research that have prompted this question are new techniques enabling culture of embryos at least up to 14 days and patterning experiments with pluripotent cells suggesting that they might form embryo-like structures. I consider each of these in relation to the foundations and function of the rule to examine whether they warrant change.</p><p><strong>Summary: </strong>I argue that the 14-day rule for embryo research should be open to change, but that this possibility must be addressed through early and thorough discussion involving a wide range of publics and other stakeholders.</p>","PeriodicalId":37444,"journal":{"name":"Current Stem Cell Reports","volume":"4 3","pages":"228-234"},"PeriodicalIF":1.4,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s40778-018-0135-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36432602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Instructive Role of the Bone Marrow Niche in Aging and Leukemia.","authors":"Elisa Lazzari, Jason M Butler","doi":"10.1007/s40778-018-0143-7","DOIUrl":"https://doi.org/10.1007/s40778-018-0143-7","url":null,"abstract":"<p><strong>Purpose of review: </strong>In this review, we aim to discuss the role of the bone marrow microenvironment in supporting hematopoiesis, with particular focus on the contribution of the endothelial niche in dictating hematopoietic stem cell (HSC) fate.</p><p><strong>Recent findings: </strong>Evidence gathered in the past two decades revealed that specific cell types within the bone marrow niche influence the hematopoietic system. Endothelial cells have emerged as a key component of the HSC niche, directly affecting stem cell quiescence, self-renewal, and lineage differentiation. Physiological alterations of the bone marrow niche occurring in aging have been described to be sufficient to promote functional aging of young HSCs. Furthermore, a growing body of evidence suggests that aberrant activation of endothelial-derived signaling pathways can aid or trigger neoplastic transformation.</p><p><strong>Summary: </strong>Several groups have contributed to the characterization of the different cell types that comprise the complex bone marrow environment, whose function was long perceived as an undiscernible sum of many parts. Further studies will need to uncover niche cell-type-specific pathways, in order to provide new targets and therapeutic options that aim at withdrawing the microenvironmental support to malignant cells while sparing normal HSCs.</p>","PeriodicalId":37444,"journal":{"name":"Current Stem Cell Reports","volume":"4 4","pages":"291-298"},"PeriodicalIF":1.4,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s40778-018-0143-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36758993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}