Adrian Konopko, Agnieszka Łukomska, Magdalena Kucia, Mariusz Z Ratajczak
{"title":"The Different Responsiveness of C3- and C5-deficient Murine BM Cells to Oxidative Stress Explains Why C3 Deficiency, in Contrast to C5 Deficiency, Correlates with Better Pharmacological Mobilization and Engraftment of Hematopoietic Cells.","authors":"Adrian Konopko, Agnieszka Łukomska, Magdalena Kucia, Mariusz Z Ratajczak","doi":"10.1007/s12015-024-10792-6","DOIUrl":"10.1007/s12015-024-10792-6","url":null,"abstract":"<p><p>The liver-derived circulating in peripheral blood and intrinsic cell-expressed complement known as complosome orchestrate the trafficking of hematopoietic stem/progenitor cells (HSPCs) both during pharmacological mobilization and homing/engraftment after transplantation. Our previous research demonstrated that C3 deficient mice are easy mobilizers, and their HSPCs engraft properly in normal mice. In contrast, C5 deficiency correlates with poor mobilization and defects in HSPCs' homing and engraftment. The trafficking of HSPCs during mobilization and homing/engraftment follows the sterile inflammation cues in the BM microenvironment caused by stress induced by pro-mobilizing drugs or myeloablative conditioning for transplantation. Therefore, to explain deficiencies in HSPC trafficking between C3-KO and C5-KO mice, we evaluated the responsiveness of C3 and C5 deficient cells to low oxidative stress. As reported, oxidative stress in BM is mediated by the activation of purinergic signaling, which is triggered by the elevated level of extracellular adenosine triphosphate (eATP) and by the activation of the complement cascade (ComC). In the current work, we noticed that BM lineage negative cells (lin<sup>-</sup>) isolated from C3-KO mice display several mitochondrial defects reflected by an impaired ability to adapt to oxidative stress. In contrast, C5-KO-derived BM cells show a high level of adaptation to this challenge. To support this data, C3-KO BM lin<sup>-</sup> cells were highly responsive to eATP stimulation, which correlates with enhanced levels of reactive oxygen species (ROS) generation and more efficient activation of intracellular Nlrp3 inflammasome. We conclude that the enhanced sensitivity of C3-KO mice cells to oxidative stress and better activation of the Nox2-ROS-Nlrp3 inflammasome signaling axis explains the molecular level differences in trafficking between C3- and C5-deficient HSPCs.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"59-67"},"PeriodicalIF":4.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11762589/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142354110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hisham Al-Ward, Wei Chen, Wenxia Gao, Chunxue Zhang, Xueyan Yang, Yao Xiong, Xinyi Wang, Rafeq Agila, Hui Xu, Yi Eve Sun
{"title":"Can miRNAs in MSCs-EVs Offer a Potential Treatment for Hypoxic-ischemic Encephalopathy?","authors":"Hisham Al-Ward, Wei Chen, Wenxia Gao, Chunxue Zhang, Xueyan Yang, Yao Xiong, Xinyi Wang, Rafeq Agila, Hui Xu, Yi Eve Sun","doi":"10.1007/s12015-024-10803-6","DOIUrl":"10.1007/s12015-024-10803-6","url":null,"abstract":"<p><p>Neonatal hypoxic-ischemic encephalopathy (HIE) is a critical condition resulting from impaired oxygen and blood flow to the brain during birth, leading to neuroinflammation, neuronal apoptosis, and long-term neurological deficits. Despite the use of therapeutic hypothermia, current treatments remain inadequate in fully preventing brain damage. Recent advances in mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) offer a novel, cell-free therapeutic approach, as these EVs can cross the blood-brain barrier (BBB) and deliver functional microRNAs (miRNAs) to modulate key pathways involved in inflammation and neuroprotection. This review examines how specific miRNAs encapsulated in MSC-EVs-including miR-21, miR-124, miR-146, and the miR-17-92 cluster-target the complex inflammatory responses that drive HIE pathology. By modulating pathways such as NF-κB, STAT3, and PI3K/Akt, these miRNAs influence neuroinflammatory processes, reduce neuronal apoptosis, and promote tissue repair. The aim is to assess the therapeutic potential of miRNA-loaded MSC-EVs in mitigating inflammation and neuronal damage, thus addressing the limitations of current therapies like therapeutic hypothermia.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"236-253"},"PeriodicalIF":4.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142584333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jiajun Xu, Weiwei Gong, Chune Mo, Xianliang Hou, Minglin Ou
{"title":"Global Knowledge Map and Emerging Research Trends in Induced Pluripotent Stem Cells and Hereditary Diseases: A CiteSpace-based Visualization and Analysis.","authors":"Jiajun Xu, Weiwei Gong, Chune Mo, Xianliang Hou, Minglin Ou","doi":"10.1007/s12015-024-10799-z","DOIUrl":"10.1007/s12015-024-10799-z","url":null,"abstract":"<p><p>The rise of induced pluripotent stem cells (iPSCs) technology has ushered in a landmark shift in the study of hereditary diseases. However, there is a scarcity of reports that offer a comprehensive and objective overview of the current state of research at the intersection of iPSCs and hereditary diseases. Therefore, this study endeavors to categorize and synthesize the publications in this field over the past decade through bibliometric methods and visual knowledge mapping, aiming to visually analyze their research focus and clinical trends. The English language literature on iPSCs and hereditary diseases, published from 2014 to 2023 in the Web of Science Core Collection (WoSCC), was examined. The CiteSpace (version 6.3.R1) software was utilized to visualize and analyze country/region, institution, scholar, co-cited authors, and co-cited journals. Additionally, the co-occurrence, clustering, and bursting of co-cited references were displayed. Analysis of 347 articles that met the inclusion criteria revealed a steady increase in the number of published articles and citation frequency in the field over the past decade. With regard to the countries/regions, institutions, scholars, and journals where the articles were published, the highest numbers were found in the USA, the University of California System, Suren M. Zakian, and Stem Cell Research, respectively. The current research is focused on the construction of disease models, both before and after correction, as well as drug target testing for single-gene hereditary diseases. Chromosome transplantation genomic therapy for hereditary diseases with abnormal chromosome structures may emerge as a future research hotspot in this field.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"126-146"},"PeriodicalIF":4.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142393477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Biological Scaffolds in 3D Cell Models: Driving Innovation in Drug Discovery.","authors":"Raj Dave, Kshipra Pandey, Ritu Patel, Nidhi Gour, Dhiraj Bhatia","doi":"10.1007/s12015-024-10800-9","DOIUrl":"10.1007/s12015-024-10800-9","url":null,"abstract":"<p><p>The discipline of 3D cell modeling is currently undergoing a surge of captivating developments that are enhancing the realism and utility of tissue simulations. Using bioinks which represent cells, scaffolds, and growth factors scientists can construct intricate tissue architectures layer by layer using innovations like 3D bioprinting. Drug testing can be accelerated and organ functions more precisely replicated owing to the precise control that microfluidic technologies and organ-on-chip devices offer over the cellular environment. Tissue engineering is becoming more dynamic with materials that can modify their surroundings with the advent of hydrogels and smart biomaterials. Advances in spheroids and organoids are not only bringing us towards more effective and customized therapies, but they are also improving their ability to resemble actual human tissues. Confocal and two-photon microscopy are examples of advanced imaging methods that provide precise images of the functioning and interaction of cells. Artificial Intelligence models have applications for enhanced scaffold designs and for predicting the response of tissues to medications. Furthermore, via strengthening predictive models, optimizing data analysis, and simplifying 3D cell culture design, artificial intelligence is revolutionizing this field. When combined, these technologies are improving our ability to conduct research and moving us toward more individualized and effective medical interventions.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"147-166"},"PeriodicalIF":4.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Manar A Elhinnawi, Michael Ibrahim Boushra, Donia Mohamed Hussien, Fatema Hesham Hussein, Islam Ahmed Abdelmawgood
{"title":"Mitochondria's Role in the Maintenance of Cancer Stem Cells in Hepatocellular Carcinoma.","authors":"Manar A Elhinnawi, Michael Ibrahim Boushra, Donia Mohamed Hussien, Fatema Hesham Hussein, Islam Ahmed Abdelmawgood","doi":"10.1007/s12015-024-10797-1","DOIUrl":"10.1007/s12015-024-10797-1","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) is the predominant form of liver cancer and is recognized as a major contributor to cancer-related mortality worldwide. Cancer stem cells (CSCs) are a tiny group of cancer cells that possess a significant ability to regenerate themselves, form tumors, and undergo differentiation. CSCs have a pivotal role in the initiation, spread, recurrence, and resistance to treatment of cancer. As a result, they are very susceptible to being targeted for therapeutic intervention. The potential to cure HCC may be achieved by efficiently targeting drugs that eradicate cancer stem cells. Mitochondria have a crucial function in granting drug resistance to cancer stem cells by means of mitochondrial metabolism, biogenesis, and dynamics. Dysfunction in mitochondrial metabolic processes, such as mitochondrial oxidative phosphorylation (OXPHOS), calcium signaling, and reactive oxygen species (ROS) generation, contributes to the initiation and progression of human malignancies, including HCC. ROS have both beneficial and detrimental effects depending on their concentration. Consequently, ROS have become a prominent subject in the study of the fundamental mechanisms of HCC. Furthermore, an imbalance in the process of creating new mitochondria is a characteristic feature of CSCs, and an increase in mitochondrial biogenesis is associated with the heightened resistance observed in CSCs. This article provides a detailed examination of the involvement of mitochondria in the preservation of CSCs, as well as the spread of HCC. A deeper understanding of how mitochondria participate in tumorigenesis and drug resistance could result in the discovery of novel cancer treatments.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"198-210"},"PeriodicalIF":4.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Retinal Organoids from Induced Pluripotent Stem Cells of Patients with Inherited Retinal Diseases: A Systematic Review.","authors":"Yoo Jin Lee, Dong Hyun Jo","doi":"10.1007/s12015-024-10802-7","DOIUrl":"10.1007/s12015-024-10802-7","url":null,"abstract":"<p><strong>Background: </strong>Currently, most inherited retinal diseases lack curative interventions, and available treatment modalities are constrained to symptomatic approaches. Retinal organoid technology has emerged as a method for treating inherited retinal diseases, with growing academic interest in recent years. The purpose of this review was to systematically organize the current protocols for generating retinal organoids using induced pluripotent stem cells from patients with inherited retinal disease and to investigate the application of retinal organoids in inherited retinal disease research.</p><p><strong>Methods: </strong>Data were collected from the PubMed, Scopus, and Web of Science databases using a keyword search. The main search term used was \"retinal organoid,\" accompanied by secondary keywords such as \"optic cup,\" \"three-dimensional,\" and \"self-organizing.\" The final search was conducted on October 2, 2024.</p><p><strong>Results: </strong>Of the 2,129 studies retrieved, 130 were included in the qualitative synthesis. The protocols for the generation of retinal organoids in inherited retinal disease research use five major approaches, categorized into 3D and a combination of 2D/3D approaches, implemented with modifications. Disease phenotypes have been successfully reproduced via the generation of retinal organoids from the induced pluripotent stem cells of individuals with inherited retinal diseases, facilitating the progression of research into novel therapeutic developments. Cells have been obtained from retinal organoids for cell therapy, and progress toward their potential integration into clinical practice is underway. Considering their potential applications, retinal organoid technology has shown promise across various domains.</p><p><strong>Conclusion: </strong>In this systematic review, we organized protocols for generating retinal organoids using induced pluripotent stem cells from patients with inherited retinal diseases. Retinal organoid technology has various applications including disease modeling, screening for novel therapies, and cell replacement therapy. Further advancements would make this technology a clinically significant tool for patients with inherited retinal diseases.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"167-197"},"PeriodicalIF":4.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11762450/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Daniel Eyraud, Aurélien Philippe, Coralie Guerin, Ignacio Sarmiento, Ludovic Suner, Louis Puybasset, Sébastien Bertil, Jean-Christophe Vaillant, Dominique Helley, Benjamin Granger, David M Smadja, Pascale Gaussem
{"title":"Cirrhotic Patients Exhibit Remarkable Vascular Regenerative Profile One Month after Liver Transplantation.","authors":"Daniel Eyraud, Aurélien Philippe, Coralie Guerin, Ignacio Sarmiento, Ludovic Suner, Louis Puybasset, Sébastien Bertil, Jean-Christophe Vaillant, Dominique Helley, Benjamin Granger, David M Smadja, Pascale Gaussem","doi":"10.1007/s12015-024-10796-2","DOIUrl":"10.1007/s12015-024-10796-2","url":null,"abstract":"","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"276-279"},"PeriodicalIF":4.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142393476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Narasimha M Beeraka, Basappa Basappa, Vladimir N Nikolenko, P A Mahesh
{"title":"Role of Neurotransmitters in Steady State Hematopoiesis, Aging, and Leukemia.","authors":"Narasimha M Beeraka, Basappa Basappa, Vladimir N Nikolenko, P A Mahesh","doi":"10.1007/s12015-024-10761-z","DOIUrl":"10.1007/s12015-024-10761-z","url":null,"abstract":"<p><p>Haematopoiesis within the bone marrow (BM) represents a complex and dynamic process intricately regulated by neural signaling pathways. This delicate orchestration is susceptible to disruption by factors such as aging, diabetes, and obesity, which can impair the BM niche and consequently affect haematopoiesis. Genetic mutations in Tet2, Dnmt3a, Asxl1, and Jak2 are known to give rise to clonal haematopoiesis of intermediate potential (CHIP), a condition linked to age-related haematological malignancies. Despite these insights, the exact roles of circadian rhythms, sphingosine-1-phosphate (S1P), stromal cell-derived factor-1 (SDF-1), sterile inflammation, and the complement cascade on various BM niche cells remain inadequately understood. Further research is needed to elucidate how BM niche cells contribute to these malignancies through neural regulation and their potential in the development of gene-corrected stem cells. This literature review describes the updated functional aspects of BM niche cells in haematopoiesis within the context of haematological malignancies, with a particular focus on neural signaling and the potential of radiomitigators in acute radiation syndrome. Additionally, it underscores the pressing need for technological advancements in stem cell-based therapies to alleviate the impacts of immunological stressors. Recent studies have illuminated the microheterogeneity and temporal stochasticity of niche cells within the BM during haematopoiesis, emphasizing the updated roles of neural signaling and immunosurveillance. The development of gene-corrected stem cells capable of producing blood, immune cells, and tissue-resident progeny is essential for combating age-related haematological malignancies and overcoming immunological challenges. This review aims to provide a comprehensive overview of these evolving insights and their implications for future therapeutic strategies.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"2-27"},"PeriodicalIF":4.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141555489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Progress in Transdifferentiation of Autologous Alternative Cell Sources into Corneal Epithelial Cells.","authors":"Bei Wang, Jiang-Lan Zhao, Wan-Ying Cai, Gong-Yue Wang, Yu-Zhi Li, Jia-Song Wang, Hua-Tao Xie, Ming-Chang Zhang","doi":"10.1007/s12015-024-10808-1","DOIUrl":"10.1007/s12015-024-10808-1","url":null,"abstract":"<p><p>Corneal limbal epithelial stem cells (LESCs) play a crucial role in corneal epithelium regeneration. Severe damage to these cells can result in limbal stem cell deficiency (LSCD), characterized by repeated corneal conjunctivalization, leading to corneal turbidity and scar formation. Restoring functional LESCs and their ecological location are essential for treating LSCD. The goal of this review is to provide researchers and clinicians with key insights into LESCs biology and to conclude the current cell-based therapies advancement in LSCD treatments. Therapeutic cell resources mainly include mesenchymal stem cells (MSCs), embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), skin keratinocyte stem cells (SKCs), and oral mucosal epithelial cells (OMECs).</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"226-235"},"PeriodicalIF":4.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11762461/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142558826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}