Stem Cell Reviews and Reports最新文献

{"title":"Mesenchymal Stem Cells Increase Resistance Against Ventricular Arrhythmias Provoked in Rats with Myocardial Infarction.","authors":"Larissa Emília Seibt, Ednei Luiz Antonio, Ighor Luiz AzevedoTeixeira, Helenita Antonia de Oliveira, André Rodrigues Lourenço Dias, Luis Felipe Neves Dos Santos, Andrey Jorge Serra","doi":"10.1007/s12015-024-10773-9","DOIUrl":"10.1007/s12015-024-10773-9","url":null,"abstract":"<p><p>This study evaluated the role of the mesenchymal stem cells derived from adipose tissue (MSCs) in provoked ventricular arrhythmias (VAs) in animals with myocardial infarction (MI). The experimental groups were: sham, subjected to sham surgery and intramyocardial saline injection; MIV, infarcted rats subjected to intramyocardial saline injection; MI + MSCs, infarcted rats subjected to intramyocardial MSCs injection. Injections were performed two days after infarction and the arrhythmogenic inducibility experiment was performed the next day. Only 35% of the MI + MSCs group developed VAs, while the one in the MIV group was 65%. The proportion of nonsustained ventricular tachycardia, sustained tachycardia, and ventricular fibrillation was similar between the infarcted groups, but MSCs animals had shorter duration of nonsustained ventricular tachycardia. However, MSCs increased connexin 43 content in the remote area, even above the levels found in the sham group. MSCs prevented the increase of IL-1β in the different areas of the myocardium. There was higher carbonylation and content of 4-hydroxynonenal (4-HNE, a marker of lipoperoxidation) in the myocardium of infarcted rats, but MSCs attenuated the increase of 4-HNE in the infarcted area. In conclusion, MSCs have a protective effect against the development of arrhythmias, but do not imply a significant benefit for animals that have developed VAs. It is possible to think that the cardioprotection of MSCs involves anti-inflammatory/oxidative actions and improvement in the formation of communicating junctions.Graphical abstract.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"2293-2302"},"PeriodicalIF":4.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142018612","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":"Comorbidities and Angiogenic Regulators Affect Endothelial Progenitor Cell Subtype Numbers in a Healthy Volunteer Control Group.","authors":"Kamini Rakkar, Rais Reskiawan A Kadir, Othman A Othman, Nikola Sprigg, Philip M Bath, Ulvi Bayraktutan","doi":"10.1007/s12015-024-10777-5","DOIUrl":"10.1007/s12015-024-10777-5","url":null,"abstract":"<p><p>Endothelial progenitor cells (EPCs) are stem cells that can repair injured blood vessels through neovascularisation. This is achieved through secretion of growth factors and endothelial maturation. EPC numbers and function have been studied to determine their diagnostic, prognostic and therapeutic potential in many ischaemic diseases such as stroke. However their activation homing and migration is not definitively understood in stroke patients. In this study, we profiled the non-stroke control group recruited into the Dunhill Medical Trust Endothelial Progenitor Cell Study. Demographic, clinical and plasma levels of angiogenic regulators of participants were analysed to determine if there was any correlation with EPC numbers, subtypes and function. Participants with diabetes had significantly supressed EPC numbers (CD45-CD34 + CD133 + KDR+) and CD34 + KDR + and KDR + EPC subtypes. Male participants had significantly lower EPC numbers compared to female participants and the proliferative capacity of endothelial colony forming cells significantly decreased with increasing participant age. Pro-angiogenic proteins such as granulocyte colony-stimulating factor and stromal cell-derived factor were positively correlated with both undifferentiated and endothelial-committed EPC subtype numbers (CD133+, KDR+, CD34 + CD133+, CD34 + KDR+), whereas anti-angiogenic proteins such as thrombospondin-1 showed a negative correlation with undifferentiated EPC subtypes (CD133+, CD34 + CD133+) but a positive correlation with endothelial-committed EPC subtype numbers (KDR+, CD34 + KDR+). These results show that EPC numbers and subtypes are affected by many factors and larger studies which can analyse and deconvolute the interactions between comorbidities, plasma biomarker levels and EPC are needed.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"2336-2344"},"PeriodicalIF":5.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11554701/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142056575","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}

{"title":"Current Non-Surgical Curative Regenerative Therapies for Knee Osteoarthritis.","authors":"Ali Bahari Golamkaboudi, Elham Vojoudi, Kosar Babaeian Roshani, Pejman Porouhan, David Houshangi, Zahra Barabadi","doi":"10.1007/s12015-024-10768-6","DOIUrl":"10.1007/s12015-024-10768-6","url":null,"abstract":"<p><p>Osteoarthritis (OA) is a prevalent musculoskeletal disease affecting middle-aged and elderly individuals, with knee pain as a common complaint. Standard therapy approaches generally attempt to alleviate pain and inflammation, using various pharmacological and non-pharmacological options. However, the efficacy of these therapies in long-term tissue repair remains debated. As an alternative, regenerative medicine offers a promising strategy, with decreased adverse event rates and increasing evidence of safety and efficacy. This review will outline current advances in regenerative medicine for knee OA, emphasizing outpatient clinic-based therapies that use orthobiological and non-biological products. Different strategies based on orthobiologics are discussed as potential regenerative options for the management of knee OA. Cell-free therapies including platelet-rich plasma, autologous anti-inflammatories, exosomes, human placenta extract, and mitochondrial transplantation are discussed, focusing on their potential for cartilage regeneration. Additionally, cell-based therapies with regenerative properties including bone marrow aspirate concentrate, adipose stromal vascular fraction, microfat, nanofat, stem cell therapy, and genetically modified cells as part of orthobiologics, are being investigated. Also, this study is looking into non-biological approaches such as using gold-induced cytokines, extracorporeal shockwave therapy, and ozone therapy. The mechanisms of action, effectiveness, and clinical applications of each therapy are being explored, providing insights into their role in the management of knee OA.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"2104-2123"},"PeriodicalIF":4.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141983252","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":"Therapeutic Applications of Engineered Mesenchymal Stromal Cells for Enhanced Angiogenesis in Cardiac and Cerebral Ischemia.","authors":"Madhavi Hegde, Abhishek Kumar Singh, Suresh Kannan, Udaykumar Kolkundkar, Raviraja N Seetharam","doi":"10.1007/s12015-024-10787-3","DOIUrl":"10.1007/s12015-024-10787-3","url":null,"abstract":"<p><p>Ischemic diseases are characterized by obstruction of blood flow to the respective organs, of which ischemia of the heart and brain are the most prominent manifestations with shared pathophysiological mechanisms and risk factors. While most revascularization therapies aim to restore blood flow, this can be challenging due to the limited therapeutic window available for treatment approaches. For a very long time, mesenchymal stromal cells have been used to treat cerebral and cardiac ischemia. However, their application is restricted either by inefficient mode of delivery or the low cell survival rates following implantation into the ischemic microenvironment. Nonetheless, several studies are currently focusing on using of mesenchymal stromal cells engineered to overexpress therapeutic genes as a cell-based gene therapy to restore angiogenesis. This review delves into the utilization of MSCs for angiogenesis and the applications of engineered MSCs for the treatment of cardiac and cerebral ischemia. Moreover, the safety issues related to the genetic modification of MSCs have also been discussed.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"2138-2154"},"PeriodicalIF":5.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11554727/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142295967","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}

{"title":"The Role of Dental-derived Stem Cell-based Therapy and Their Derived Extracellular Vesicles in Post-COVID-19 Syndrome-induced Tissue Damage.","authors":"Mitra Rostami, Pouria Farahani, Samar Esmaelian, Zahra Bahman, Abbas Fadel Hussein, Hareth A Alrikabi, Mohammad Hosseini Hooshiar, Saman Yasamineh","doi":"10.1007/s12015-024-10770-y","DOIUrl":"10.1007/s12015-024-10770-y","url":null,"abstract":"<p><p>Long coronavirus disease 2019 (COVID-19) is linked to an increased risk of post-acute sequelae affecting the pulmonary and extrapulmonary organ systems. Up to 20% of COVID-19 patients may proceed to a more serious form, such as severe pneumonia, acute respiratory distress syndrome (ARDS), or pulmonary fibrosis. Still, the majority of patients may only have mild, self-limiting sickness. Of particular concern is the possibility of parenchymal fibrosis and lung dysfunction in long-term COVID-19 patients. Furthermore, it has been observed that up to 43% of individuals hospitalized with COVID-19 also had acute renal injury (AKI). Care for kidney, brain, lung, cardiovascular, liver, ocular, and tissue injuries should be included in post-acute COVID-19 treatment. As a powerful immunomodulatory tool in regenerative medicine, dental stem cells (DSCs) have drawn much interest. Numerous immune cells and cytokines are involved in the excessive inflammatory response, which also has a significant effect on tissue regeneration. A unique reservoir of stem cells (SCs) for treating acute lung injury (ALI), liver damage, neurological diseases, cardiovascular issues, and renal damage may be found in tooth tissue, according to much research. Moreover, a growing corpus of in vivo research is connecting DSC-derived extracellular vesicles (DSC-EVs), which are essential paracrine effectors, to the beneficial effects of DSCs. DSC-EVs, which contain bioactive components and therapeutic potential in certain disorders, have been shown as potentially effective therapies for tissue damage after COVID-19. Consequently, we explore the properties of DSCs in this work. Next, we'll look at how SARS-CoV-2 affects tissue damage. Lastly, we have looked at the use of DSCs and DSC-EVs in managing COVID-19 and chronic tissue damage, such as injury to the heart, brain, lung, and other tissues.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"2062-2103"},"PeriodicalIF":4.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141988933","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":"Study on Preclinical Safety and Toxic Mechanism of Human Umbilical Cord Mesenchymal Stem Cells in F344RG Rats.","authors":"Xiaofang Hao, Hao Zhu, Chao Qin, Lulu Li, Zhi Lin, Hua Jiang, Qianqian Li, Yan Huo, Hezhan Zhang, Xingchao Geng, Ying Huang, Bo Li","doi":"10.1007/s12015-024-10780-w","DOIUrl":"10.1007/s12015-024-10780-w","url":null,"abstract":"<p><p>Mesenchymal stem cells have made remarkable progress in recent years. Many studies have reported that human umbilical cord mesenchymal stem cells (hUC-MSCs) have no toxicity, but thromboembolism appeared in patients treated with hUC-MSCs. Therefore, people are still worried about the safety of clinical application. The study aims to determine the safety, potential toxic mechanism and biodistribution of hUC-MSCs. F344RG rats were given 5 or 50 million cells/kg of hUC-MSCs by single administration in compliance with Good Laboratory Practice standards. Standard toxicity was performed. RNA sequencing was then performed to explore the potential toxic mechanisms. In parallel, the biodistribution of hUC-MSCs was examined. The dose of 5 million cells/kg hUC-MSCs had no obvious toxicity on symptom, weight, food intake, hematology, serum biochemistry, urine biochemistry, cytokines, and histopathology. However, blood-tinged secretions in the urethral orifice and 20% mortality occurred at 50 million cells/kg. Disseminated intravascular coagulopathy (DIC) is the leading cause of death. hUC-MSCs significantly upregulated complement and coagulation cascade pathways gene expression, resulting in DIC. Besides, hUC-MSCs upregulated fibrinolytic system suppressor genes A2m, Serping1 and Serpinf2. hUC-MSCs survived in rats for less than 28 days, no hUC-MSC was detected in tissues outside the lungs. There was no toxicity in F344RG rats at 5 million cells/kg, but some toxicities were detected at 50 million cells/kg. hUC-MSCs significantly upregulated complement and coagulation cascade pathways, upregulated the expression of fibrinolytic system suppressor genes A2m, Serping1 and Serpinf2, to inhibit fibrinolytic system, caused DIC, which provided a new insight into the toxic mechanism of hUC-MSCs.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"2236-2252"},"PeriodicalIF":5.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11554750/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142146377","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}

{"title":"Recent Advances in Basic Studies of Low-Intensity Pulsed Ultrasound in Periodontal Tissue Regeneration: A Systematic Review.","authors":"Facai Li, Yujiao Li, Yuan Zhu, Xiaomei Bao, Lei Wang","doi":"10.1007/s12015-024-10769-5","DOIUrl":"10.1007/s12015-024-10769-5","url":null,"abstract":"<p><p>Approximately half of the adult population is suffering from periodontal disease, and conventional periodontal treatment strategies can only slow the progression of the disease. As a kind of tissue engineering, periodontal regeneration brings hope for the treatment of periodontal disease. Low-intensity pulsed ultrasound (LIPUS) is a form of ultrasound with a frequency of 1-3 MHz and a much lower intensity (< 1W/cm²) than traditional ultrasound energy and output. LIPUS has been adopted for a variety of therapeutic purposes due to its bioeffects such as thermal, mechanical, and cavitation effects, which induce intracellular biochemical effects and lead to tissue repair and regeneration ultimately. In this systematic review, we summarize the basic research of LIPUS in the treatment of periodontal disease in periodontal disease animal models and the influence of LIPUS on the biological behavior (including promoting osteogenic differentiation of stem cells and inhibiting inflammatory response) and potential mechanism of periodontal ligament stem cells (PDLSCs), hoping to provide new ideas for the treatment of periodontal disease. We believe that LIPUS can be used as an auxiliary strategy in the treatment of periodontal disease and play an exciting and positive role in periodontal regeneration.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"2124-2137"},"PeriodicalIF":4.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141971870","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":"Exosomal Drug Delivery Systems: A Novel Therapy Targeting PD-1 in Septic-ALI.","authors":"Yuanlan Huang, Gang Li, Zeqi Chen, Mengying Chen, Weibin Zhai, Dan Li, Qingqiang Xu","doi":"10.1007/s12015-024-10784-6","DOIUrl":"10.1007/s12015-024-10784-6","url":null,"abstract":"<p><strong>Background: </strong>The cytokine storm triggered by sepsis can lead to the development of acute lung injury (ALI). Human umbilical cord Mesenchymal stem cells derived exosomes (HucMSCs-EXOs) have been demonstrated to possess immunosuppressive and anti-inflammatory properties. Programmed cell death receptor 1 (PD-1) plays a crucial role in maintaining the inflammatory immune homeostasis. The aim of this study is to investigate the synergistic therapeutic effect of EXOs loaded with anti-PD-1 peptide on septic-ALI.</p><p><strong>Methods: </strong>This study prepares a novel EXOs-based drug, named MEP, by engineering modification of HucMSCs-EXOs, which are non-immunogenic extracellular vesicles, loaded with anti-PD-1 peptide. The therapeutic effect and potential mechanism of MEP on septic-ALI are elucidated through in vivo and in vitro experiments, providing experimental evidence for the treatment of septic acute lung injury with MEP.</p><p><strong>Results: </strong>We found that, compared to individual components (anti-PD-1 peptide or EXOs), MEP treatment can more effectively improve the lung injury index of septic-ALI mice, significantly reduce the expression levels of inflammatory markers CRP and PCT, as well as pro-inflammatory cytokines TNF-α and IL-1β in serum, decrease lung cell apoptosis, and significantly increase the expression of anti-inflammatory cytokine IL-10 and CD68⁺ macrophages. In vitro, MEP co-culture promotes the proliferation of CD206⁺ macrophages, increases the M2/M1 macrophage ratio, and attenuates the inflammatory response. GEO data analysis and qRT-PCR validation show that MEP reduces the expression of inflammasome-related genes and M1 macrophage marker iNOS.</p><p><strong>Conclusion: </strong>In both in vitro and in vivo settings, MEP demonstrates superior therapeutic efficacy compared to individual components in the context of septic-ALI.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"2253-2267"},"PeriodicalIF":4.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142135094","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":"Trophoblast Side-Population Markers are Dysregulated in Preeclampsia and Fetal Growth Restriction.","authors":"Georgia P Wong, Sunhild Hartmann, David G Simmons, Sarah Ellis, Olivia Nonn, Ping Cannon, Tuong-Vi Nguyen, Anna Nguyen, Lucy A Bartho, Stephen Tong, Natalie J Hannan, Tu'uhevaha J Kaitu'u-Lino","doi":"10.1007/s12015-024-10764-w","DOIUrl":"10.1007/s12015-024-10764-w","url":null,"abstract":"<p><p>Dysregulated progenitor cell populations may contribute to poor placental development and placental insufficiency pathogenesis. Side-population cells possess progenitor properties. Recent human trophoblast side-population isolation identified enrichment of 8 specific genes (CXCL8, ELL2, GATA6, HK2, HLA-DPB1, INTS6, SERPINE3 and UPP1) (Gamage et al. 2020, Stem Cell Rev Rep). We characterised these trophoblast side-population markers in human placenta and in placental insufficiency disorders: preeclampsia and fetal growth restriction (FGR). Trophoblast side-population markers localised to mononuclear trophoblasts lining the placental villous basement membrane in preterm control, preeclamptic and FGR placental sections (n = 3, panel of 3 markers/serial section). Analysis of single-cell transcriptomics of an organoid human trophoblast stem cell (hTSC) to extravillous trophoblast (EVT) differentiation model (Shannon et al. 2022, Development) identified that all side-population genes were enriched in mononuclear trophoblast and trophoblasts committed to differentiation under hTSC culture conditions. In vitro validation via 96 h time course hTSC differentiation to EVTs or syncytiotrophoblasts (n = 5) demonstrated ELL2 and HK2 increased with differentiation (p < 0.0024, p < 0.0039 respectively). CXCL8 and HLA-DPB1 were downregulated (p < 0.030, p < 0.011 respectively). GATA6 and INTS6 increased with EVT differentiation only, and UPP1 reduced with syncytialisation. SERPINE3 was undetectable. Trophoblast side-population marker mRNA was measured in human placentas (< 34-weeks' gestation; n = 78 preeclampsia, n = 30 FGR, and n = 18 gestation-matched controls). ELL2, HK2 and CXCL8 were elevated in preeclamptic (p = 0.0006, p < 0.0001, p = 0.0335 respectively) and FGR placentas (p = 0.0065, p < 0.0001, p = 0.0001 respectively) versus controls. Placental GATA6 was reduced in pregnancies with preeclampsia and FGR (p = 0.0014, p = 0.0146 respectively). Placental INTS6 was reduced with FGR only (p < 0.0001). This study identified the localisation of a unique trophoblast subset enriched for side-population markers. Aberrant expression of some side-population markers may indicate disruptions to unique trophoblast subtypes in placental insufficiency.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"1954-1970"},"PeriodicalIF":4.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11445292/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141724508","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}

{"title":"Generation and Characterization of Induced Pluripotent Stem Cells Carrying An ASXL1 Mutation.","authors":"Wenjun Wang, Xiaoru Zhang, Yunan Li, Jun Shen, Yihan Li, Wen Xing, Jie Bai, Jun Shi, Yuan Zhou","doi":"10.1007/s12015-024-10737-z","DOIUrl":"10.1007/s12015-024-10737-z","url":null,"abstract":"<p><p>Additional sex combs-like 1 (ASXL1) is an epigenetic modulator frequently mutated in myeloid malignancies, generally associated with poor prognosis. Current models for ASXL1-mutated diseases are mainly based on the complete deletion of Asxl1 or overexpression of C-terminal truncations in mice models. However, these models cannot fully recapitulate the pathogenesis of myeloid malignancies. Patient-derived induced pluripotent stem cells (iPSCs) provide valuable disease models that allow us to understand disease-related molecular pathways and develop novel targeted therapies. Here, we generated iPSCs from a patient with myeloproliferative neoplasm carrying a heterozygous ASXL1 mutation. The iPSCs we generated exhibited the morphology of pluripotent cells, highly expressed pluripotent markers, excellent differentiation potency in vivo, and normal karyotype. Subsequently, iPSCs with or without ASXL1 mutation were induced to differentiate into hematopoietic stem/progenitor cells, and we found that ASXL1 mutation led to myeloid-biased output and impaired erythroid differentiation. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses showed that terms related to embryonic development, myeloid differentiation, and immune- and neural-related processes were most enriched in the differentially expressed genes. Western blot demonstrated that the global level of H2AK119ub was significantly decreased when mutant ASXL1 was present. Chromatin Immunoprecipitation Sequencing showed that most genes associated with stem cell maintenance were upregulated, whereas occupancies of H2AK119ub around these genes were significantly decreased. Thus, the iPSC model carrying ASXL1 mutation could serve as a potential tool to study the pathogenesis of myeloid malignancies and to screen targeted therapy for patients.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"1889-1901"},"PeriodicalIF":4.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141331669","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}