Stem Cell Research & Therapy最新文献

{"title":"Transcriptome-aligned metabolic profiling by SERSome reflects biological changes following mesenchymal stem cells expansion.","authors":"Xinyuan Bi, Bin Ma, Wei Liu, Wei-Qiang Gao, Jian Ye, Hanyu Rao","doi":"10.1186/s13287-024-04109-0","DOIUrl":"10.1186/s13287-024-04109-0","url":null,"abstract":"<p><strong>Background: </strong>Mesenchymal stem cells (MSCs) are widely applied in the treatment of various clinical diseases and in the field of medical aesthetics. However, MSCs exhibit greater heterogeneity limited stability, and more complex molecular and mechanistic characteristics compared to conventional drugs, making rapid and precise monitoring more challenging.</p><p><strong>Methods: </strong>Surface-enhanced Raman spectroscopy (SERS) is an ultrasensitive, tractable and low-cost fingerprinting technique capable of identifying a wide range of molecules related to biological processes. Here, we employed SERS for reproducible quantification of ultralow concentrations of molecules and utilized spectral sets, termed SERSomes, for robust and comprehensive intracellular multi-metabolite profiling.</p><p><strong>Results: </strong>We revealed that with increasing passage number, there is a gradual decline in cell expansion efficiency, accompanied by significant changes in intracellular amino acids, purines, and pyrimidines. By integrating these metabolic features detected by SERS with transcriptomic data, we established a correlation between SERS signals and biological changes, as well as differentially expressed genes.</p><p><strong>Conclusion: </strong>In this study, we explore the application of SERS technique to provide robust metabolic characteristics of MSCs across different passages and donors. These results demonstrate the effectiveness of SERSome in reflecting biological characteristics. Due to its sensitivity, adaptability, low cost, and feasibility for miniaturized instrumentation throughout pretreatment, measurement, and analysis, the label-free SERSome technique is suitable for monitoring MSC expansion and offers significant advantages for large-scale MSC manufacturing.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"15 1","pages":"467"},"PeriodicalIF":7.1,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11656856/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142855251","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}

{"title":"An hiPSC-CM approach for electrophysiological phenotyping of a patient-specific case of short-coupled TdP.","authors":"Willem B van Ham, Esmeralda E M Meijboom, Merel L Ligtermoet, Jantine Monshouwer-Kloots, Anneline S J M Te Riele, Folkert W Asselbergs, Eva van Rooij, Mimount Bourfiss, Toon A B van Veen","doi":"10.1186/s13287-024-04074-8","DOIUrl":"10.1186/s13287-024-04074-8","url":null,"abstract":"<p><strong>Introduction: </strong>A healthy young woman, age 26 without prior cardiac complications, experienced an out-of-hospital cardiac arrest caused by ventricular fibrillation (VF), which coincided with a fever. Comprehensive diagnostics including echo, CMR, exercise testing, and genetic sequencing, did not identify any potential cause. This led to the diagnosis of idiopathic VF and installment of an implantable cardioverter defibrillator, which six months later appropriately intervened another VF episode under conditions comparable to the first event. A second diagnostic opinion concluded short-coupled Torsade de Pointes (scTdP), and the patient was started on a verapamil treatment.</p><p><strong>Methods: </strong>From this patient, human induced pluripotent stem cell cardiomyocyte (hiPSC-CM) lines were generated to study cellular electrophysiology. Without a known genetic pathogenic variation, no isogenic control line could be produced, therefore a healthy age- and sex-matched control hiPSC-CM line was used. Cellular electrophysiology was studied in these cardiomyocytes using calcium- and voltage sensitive fluorescent dyes and measurements were carried out at 37 °C and 39 °C, to mimic the condition of hyperthermia in the patient. mRNA expression of electrophysiologically relevant genes were analyzed to identify a potential underlying mechanism.</p><p><strong>Results: </strong>Calcium transients measured in patient lines at a physiological temperature indicated the occurrence of early after transients (EATs). Strikingly, at 39 °C the incidence of EATs further increased. Membrane potential data from the patient also revealed shorter action potentials that, combined with the EATs, indicate the premature release of calcium during diastole, which could be responsible for the extrasystoles in the patient. Gene expression profiles were mainly downregulated in the patient but could not clearly aid in unraveling a mechanism behind the occurrence of EATs. Pharmacological screening was performed to evaluate the treatment regimen and to determine a mechanism of action of the EATs. While verapamil, dantrolene, and flecainide did not decrease the incidence of EATs, calcium handling parameters were affected indicating functionality of the drugs.</p><p><strong>Conclusion: </strong>This patient-specific case of electrophysiological phenotyping resulted in a hypothesis of the possible mechanism behind the scTdP arrhythmias, but also accentuates the applicability of patient-specific hiPSC-CM disease modeling and phenotyping.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"15 1","pages":"470"},"PeriodicalIF":7.1,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11656816/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142855364","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}

{"title":"Human platelet lysate enhances small lipid droplet accumulation of human MSCs through MAPK phosphorylation.","authors":"Ping Du, Xuelian Tao, Javad Harati, Yue Shi, Liang Xiao, Xian Li, Haobo Pan, Peng-Yuan Wang","doi":"10.1186/s13287-024-04085-5","DOIUrl":"10.1186/s13287-024-04085-5","url":null,"abstract":"<p><strong>Background: </strong>Human platelet lysate (hPL) has emerged as a promising serum substitute to enhance the self-renewal and multipotency of human mesenchymal stem cells (MSCs). Despite its potential, the specific biological mechanisms by which hPL influences MSC phenotypes remain inadequately understood.</p><p><strong>Methods: </strong>We investigated the biological signaling activated by hPL in two common types of human MSCs: bone marrow-derived MSCs (BMSCs) and adipose-derived MSCs (ASCs). Cell adhesion and cell-matrix interaction were assessed through immunofluorescence staining and western blotting. The impact of hPL on lipid droplet formation in MSCs was thoroughly examined using oil red O/BODIPY staining, semi-quantitative analysis, and qRT-PCR. RNA sequencing and intracellular inhibition assays were also performed to elucidate the mechanisms by which hPL modulates MSC behavior.</p><p><strong>Results: </strong>MSCs cultured in hPL medium demonstrated a reduction in cell size, spreading area, and vinculin puncta,  while enhancing cell proliferation and lipid droplet accumulation compared to those cultured in control media. Notably, the lipid droplets in hPL-treated MSCs were significantly smaller than those in adipocyte-like cells differentiated from MSCs, highlighting hPL's distinctive role in lipid production. Gene and protein expression profiles of hPL-treated MSCs differed from those in adipocyte-like cells. An angiogenic factor array revealed that hPL-MSCs had a distinct angiogenic factor profile compared to FBS-MSCs, with VEGF expression closely linked to HIF-1α expression. RNA-seq data identified approximately 1,900 differentially expressed genes (DEGs) between hPL-MSCs and FBS-MSCs, with enrichment in focal adhesion, ECM-receptor interaction, and PI3K-Akt/MAPK signaling pathways. Inhibition of MAPK phosphorylation significantly hampered lipid formation in hPL-MSCs, underscoring the pivotal role of MAPK signaling in hPL-driven adipogenesis.</p><p><strong>Conclusion: </strong>This study reveals the biological mechanisms by which hPL infleunces MSC behavior and differentiation, offering new insights into its potential application in regenerative medicine and tissue engineering.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"15 1","pages":"473"},"PeriodicalIF":7.1,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11656580/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142855414","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}

{"title":"Manipulated mesenchymal stem cell therapy in the treatment of Parkinson's disease.","authors":"Seyedeh Toktam Ekrani, Mahmoud Mahmoudi, Dariush Haghmorad, Ramiar Kamal Kheder, Alireza Hatami, Seyed-Alireza Esmaeili","doi":"10.1186/s13287-024-04073-9","DOIUrl":"10.1186/s13287-024-04073-9","url":null,"abstract":"<p><p>Mesenchymal stem cell (MSC) therapy has been considered a promising approach for the treatment of Parkinson's disease (PD) for several years. PD is a globally prevalent neurodegenerative disease characterized by the accumulation of Lewy bodies and the loss of dopaminergic neurons, leading to severe motor and non-motor complications in patients. As current treatments are unable to halt the progression of neuronal loss and dopamine degradation, MSC therapy has emerged as a highly promising strategy for PD treatment. This promise is due to MSCs' unique properties compared to other types of stem cells, including self-renewal, differentiation potential, immune privilege, secretion of neurotrophic factors, ability to improve damaged tissue, modulation of the immune system, and lack of ethical concerns. MSCs have been employed in numerous pre-clinical and clinical studies for PD treatment with promising results. However, certain aspects of their efficacy in treating PD may benefit from various genetic and epigenetic modifications. In this review article, we assess these approaches to improving MSCs for specialized treatment of PD.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"15 1","pages":"476"},"PeriodicalIF":7.1,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11657756/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142855441","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}

{"title":"Umbilical cord-derived mesenchymal stem cells preferentially modulate macrophages to alleviate pulmonary fibrosis.","authors":"Meng Li, Jun Li, Ying Wang, Guancheng Jiang, Hanguo Jiang, Mengdi Li, Ziying Zhu, Fangli Ren, Yinyin Wang, Muyang Yan, Zhijie Chang","doi":"10.1186/s13287-024-04091-7","DOIUrl":"10.1186/s13287-024-04091-7","url":null,"abstract":"<p><strong>Background: </strong>Idiopathic Pulmonary Fibrosis (IPF) is a type of interstitial lung disease characterized by chronic inflammation due to persistent lung damage. Mesenchymal stem cells (MSCs), including those derived from the umbilical cord (UCMSCs) and placenta (PLMSCs), have been utilized in clinical trials for IPF treatment. However, the varying therapeutic effectiveness between these two MSC types remains unclear.</p><p><strong>Methods: </strong>In this study, we examined the therapeutic differences between UCMSCs and PLMSCs in treating lung damage using a bleomycin (BLM)-induced pulmonary injury mouse model.</p><p><strong>Results: </strong>We showed that UCMSCs had a superior therapeutic impact on lung damage compared to PLMSCs. Upon cytokine stimulation, UCMSCs expressed higher levels of inflammation-related genes and more effectively directed macrophage polarization towards the M2 phenotype than PLMSCs, both in vitro and in vivo. Furthermore, UCMSCs showed a preference for expressing CC motif ligation 2 (CCL2) and C-X-C motif chemokine ligand 1 (CXCL1) compared to PLMSCs. The expression of secreted phosphoprotein 1 (SPP1), triggering receptor expressed on myeloid cells 2 (Trem2), and CCAAT enhancer binding protein beta (Cebpb) in macrophages from mice with the disease treated with UCMSCs was significantly reduced compared to those treated with PLMSCs.</p><p><strong>Conclusions: </strong>Therefore, UCMSCs demonstrated superior anti-fibrotic abilities in treating lung damage, potentially through inducing a more robust M2 polarization of macrophages than PLMSCs.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"15 1","pages":"475"},"PeriodicalIF":7.1,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11657361/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142855215","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}

{"title":"Hypoxic mesenchymal stem cell-derived exosomal circDennd2a regulates granulosa cell glycolysis by interacting with LDHA.","authors":"Wenxin Li, Minjun Lu, Junyu Shang, Jiamin Zhou, Li Lin, Yueqin Liu, Dan Zhao, Xiaolan Zhu","doi":"10.1186/s13287-024-04098-0","DOIUrl":"10.1186/s13287-024-04098-0","url":null,"abstract":"<p><strong>Background: </strong>Premature ovarian insufficiency (POI) is an ovarian dysfunction disorder that significantly impacts female fertility. Ovarian granulosa cells (GCs) are crucial somatic components supporting oocyte development that rely on glycolysis for energy production, which is essential for follicular growth. Hypoxia-induced exosomal circRNAs regulate glycolysis, but their biological functions and molecular mechanisms in POI are largely unexplored. The present comprehensive investigation revealed a substantial reduction in ovarian glycolysis levels in POI rats. Notably, hypoxia-induced exosomes originating from mesenchymal stem cells (HM-Exs) exhibit a remarkable capacity to enhance ovarian glycolysis, mitigate GCs apoptosis, reinstate disrupted estrous cycles, modulate sex hormone levels, and curtail the presence of atretic follicles. These restorative actions collectively contribute to fostering fertility revival in POI-afflicted rats.</p><p><strong>Methods: </strong>Cyclophosphamide was administered for 2 weeks to induce POI rat model, and POI rats were randomly divided into three groups and treated with PBS, NM-Exs and HM-Exs, respectively. Ovarian function and fertility were assessed at the end of the study and ovarian tissues were collected for analysis of energy metabolites. The relationship between circDennd2a and POI was explored in vitro by qRT-PCR, Western blotting, CCK-8 assay, EdU staining, TUNEL staining, extracellular acidification rate (ECAR) measurements, and ATP, lactate and pyruvate level assays.</p><p><strong>Results: </strong>Our findings revealed depletion of circDennd2a in serum samples and GCs from individuals suffering from POI. The introduction of HM-Exs-derived circDennd2a (HM-Exs-circDennd2a) effectively counteracted GCs apoptosis by enhancing glycolytic processes and driving cellular proliferation. CircDennd2a interacted with lactate dehydrogenase A (LDHA), which served as a catalyst to increase LDHA enzymatic activity and facilitate the conversion of NADH to NAD+. This biochemical cascade worked synergistically to sustain glycolytic function within GCs.</p><p><strong>Conclusion: </strong>This study revealed that HM-Exs-circDennd2a promoted LDHA activity and enhanced GCs glycolytic capacity, both of which support its use as a potential clinical diagnostic and therapeutic target for POI.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"15 1","pages":"484"},"PeriodicalIF":7.1,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11657290/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142855418","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}

{"title":"Transcriptomic and proteomic sequencing unveils the role of vitamin D and metabolic flux shifts in the induction of human hepatic organoids.","authors":"Shule Zhang, Linghong Liu, Xianyu Li, Tiancheng Zhou, Qing Shi, Dong Li, Xiuli Ju","doi":"10.1186/s13287-024-04101-8","DOIUrl":"10.1186/s13287-024-04101-8","url":null,"abstract":"<p><strong>Background: </strong>Hepatic organoids (HOs), validated through comparative sequencing with human liver tissues, are reliable models for liver research. Comprehensive transcriptomic and proteomic sequencing of HOs throughout their induction period will enhance the platform's utility, aiding in the elucidation of liver development's molecular mechanisms.</p><p><strong>Methods: </strong>We developed hepatic organoids (HOs) from embryonic stem cells (ESCs) through a de novo induction protocol, mimicking the stages of fetal liver development: ESCs to definitive endoderm (DE), then to foregut (FG), hepatoblasts (HB), and finally to HOs stage 1 (HO1), culminating in self-organizing HOs stage 2 (HO2) via dissociation and re-inoculation. The successful establishment of HOs was validated by immunofluorescence staining and RT-qPCR for specific markers. Comprehensive transcriptomic and proteomic sequencing and analysis were conducted on FG, HB, HO1, and HO2.</p><p><strong>Results: </strong>Our data suggest that several transcription factors (TFs) activated during the HB stage share overlapping target genes with the vitamin D receptor (VDR). Calcitriol, a direct activator of VDR, notably facilitated the FG to HB stage transition by activating VDR and enhancing key TFs, thereby promoting hepatic progenitor cell maturation. Furthermore, our findings revealed a significant transition towards glycolytic energy metabolism at the HO2 stage, characterized by increased glycolytic flux and reduced oxidative phosphorylation. Inhibition of glycolysis using 2-deoxy-D-glucose (2-DG) led to suppressed growth and differentiation at the HO2 stage. Analysis of signaling pathways indicated upregulation of the HIF-1 pathway, which is associated with glycolysis activation, as well as the MAPK and PI3K-AKT pathways, which regulate HIF-1α protein translation.</p><p><strong>Conclusions: </strong>We elucidated a pivotal role for calcitriol in facilitating the transition from FG to HB by activating VDR and augmenting the expression of critical transcription factors (TFs). Besides, our research underscores a shift in metabolic pathways toward glycolytic energy metabolism in HO2 organoids. Overall, our multiomics approach reveals the intricate molecular regulation during the development of HOs.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"15 1","pages":"478"},"PeriodicalIF":7.1,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11657659/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142855279","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}

{"title":"ZO-1 boosts the in vitro self-renewal of pre-haematopoietic stem cells from OCT4-reprogrammed human hair follicle mesenchymal stem cells through cytoskeleton remodeling.","authors":"Yingchun Ruan, Xingang Huang, Pengpeng Sun, Xiaozhen Yu, Xiaohua Tan, Yaolin Song, Hua Chen, Zhijing Liu","doi":"10.1186/s13287-024-04080-w","DOIUrl":"10.1186/s13287-024-04080-w","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;The challenge of expanding haematopoietic stem/progenitor cells (HSPCs) in vitro has limited their clinical application. Human hair follicle mesenchymal stem cells (hHFMSCs) can be reprogrammed to generate intermediate stem cells by transducing OCT4 (hHFMSCs&lt;sup&gt;OCT4&lt;/sup&gt;) and pre-inducing with FLT3LG/SCF, and differentiated into erythrocytes. These intermediate cells exhibit gene expression patterns similar to pre-HSCs, making them promising for artificial haematopoiesis. However, further investigation is required to elucidate the in vitro proliferation ability and mechanism underlying the self-renewal of pre-HSCs derived from hHFMSCs.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;hHFMSCs&lt;sup&gt;OCT4&lt;/sup&gt; were pre-treated with FLT3LG and SCF cytokines, followed by characterization and isolation of the floating cell subsets for erythroid differentiation through stimulation with hematopoietic cytokines and nutritional factors. Cell adhesion was assessed through disassociation and adhesion assays. OCT4 expression levels were measured using immunofluorescence staining, RT-qPCR, and Western blotting. RNA sequencing and Gene Ontology (GO) enrichment analysis were then conducted to identify proliferation-related biological processes. Proliferative capacity was evaluated through CCK-8, colony formation assays, Ki67 index, and cell cycle analysis. Cytoskeleton was observed through Wright‒Giemsa, Coomassie brilliant blue, and phalloidin staining. Expression of adherens junction (AJ) core members was confirmed through RT‒qPCR, Western blotting, and immunofluorescence staining before and after ZO-1 knockdown. A regulatory network was constructed to determine relationships among cytoskeleton, proliferation, and the AJ pathway. Student's t tests (GraphPad Prism 8.0.2) were used for group comparisons. The results were considered significant at P &lt; 0.05.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Pre-treatment of hHFMSCs&lt;sup&gt;OCT4&lt;/sup&gt; with FLT3LG and SCF leads to the emergence of floating cell subsets exhibiting small, globoid morphology, suspended above adherent cells, forming colonies, and displaying minimal expression of CD45. Excessive OCT4 expression weakens adhesion in floating hHFMSCs&lt;sup&gt;OCT4&lt;/sup&gt;. Floating cells moderately enhanced proliferation and undergo cytoskeleton remodelling, with increased contraction and aggregation of F-actin near the nucleus. The upregulation of ZO-1 could impact the expressions of F-actin, E-cadherin, and β-catenin genes, as well as the nuclear positioning of β-catenin, leading to variations in the cytoskeleton and cell cycle. Finally, a regulatory network revealed that the AJ pathway cored with ZO-1 critically bridges cytoskeletal remodelling and haematopoiesis-related proliferation in a β-catenin-dependent manner.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;ZO-1 improved the self-renewal of pre-HSCs from OCT4-overexpressing hHFMSCs by remodeling the cytoskeleton via the ZO-1-regulated AJ pathway, suggesting floating hHFMS","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"15 1","pages":"480"},"PeriodicalIF":7.1,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11658245/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142855329","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}

{"title":"Advances in genetically modified neural stem cell therapy for central nervous system injury and neurological diseases.","authors":"Xiangwen Tang, Peng Deng, Lin Li, Yuqing He, Jinchao Wang, Dingjun Hao, Hao Yang","doi":"10.1186/s13287-024-04089-1","DOIUrl":"10.1186/s13287-024-04089-1","url":null,"abstract":"<p><p>Neural stem cells (NSCs) have increasingly been recognized as the most promising candidates for cell-based therapies for the central nervous system (CNS) injuries, primarily due to their pluripotent differentiation capabilities, as well as their remarkable secretory and homing properties. In recent years, extensive research efforts have been initiated to explore the therapeutic potential of NSC transplantation for CNS injuries, yielding significant advancements. Nevertheless, owing to the formation of adverse microenvironment at post-injury leading to suboptimal survival, differentiation, and integration within the host neural network of transplanted NSCs, NSC-based transplantation therapies often fall short of achieving optimal therapeutic outcomes. To address this challenge, genetic modification has been developed an attractive strategy to improve the outcomes of NSC therapies. This is mainly attributed to its potential to not only enhance the differentiation capacity of NSCs but also to boost a range of biological activities, such as the secretion of bioactive factors, anti-inflammatory effects, anti-apoptotic properties, immunomodulation, antioxidative functions, and angiogenesis. Furthermore, genetic modification empowers NSCs to play a more robust neuroprotective role in the context of nerve injury. In this review, we will provide an overview of recent advances in the roles and mechanisms of NSCs genetically modified with various therapeutic genes in the treatment of neural injuries and neural disorders. Also, an update on current technical parameters suitable for NSC transplantation and functional recovery in clinical studies are summarized.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"15 1","pages":"482"},"PeriodicalIF":7.1,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11656587/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142855357","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}

{"title":"Immunomodulatory features of MSC-derived exosomes decorated with DC-specific aptamer for improving sublingual immunotherapy in allergic mouse model.","authors":"Mahvash Sadeghi, Sajad Dehnavi, Ali Khodadadi, Ata A Ghadiri, Ali Ganji, Moosa Sharifat, Ali Asadirad","doi":"10.1186/s13287-024-04099-z","DOIUrl":"10.1186/s13287-024-04099-z","url":null,"abstract":"<p><strong>Introduction: </strong>Sublingual immunotherapy (SLIT) is an effective and injection-free route for allergen-specific immunotherapy (AIT). Mesenchymal stromal/stem cell (MSC)-derived exosomes (Exo) has been identified as a novel delivery platform with immunomodulatory capacities. In addition, targeting agents such as aptamers (Apt) have been extensively used for specific delivery approaches such as direct delivery of allergen formulations to dendritic cells (DC) to improve the efficacy of specific immunotherapy. In this study, we assessed the effects of MSC-derived Exos containing ovalbumin (Ova) which decorated with DC-specific aptamer in allergic rhinitis mice model.</p><p><strong>Materials and methods: </strong>Exos were harvested from adipose tissue-derived MSCs, and Exo-Apt-Ova complex was formulated. Then, Ova-induced allergic asthma model was simulated and sensitized BALB/c mice were treated sublingually with Exo-Apt-Ova complex (5 µg Ova) twice weekly for 8 weeks. Ova-specific IgE levels in serum and concentrations of interferon-gamma (IFN-γ), interleukin (IL)-4, and transforming growth factor-beta (TGF-β) in the supernatant of cultured splenocytes were evaluated using enzyme-linked immunosorbent assay (ELISA). In addition, lung histologic analysis and nasopharyngeal lavage fluid (NALF) cell count were performed.</p><p><strong>Results: </strong>Administration of Ova-incorporated Apt-modified Exos dramatically increased IFN-γ and TGF-β levels, and decreased IL-4 and IgE levels. In addition, inflammatory responses in the lung tissue and the number of eosinophils in NALF decreased.</p><p><strong>Conclusion: </strong>SLIT using Exo-Ova (5 µg) decorated with DC-specific aptamer induced immunomodulatory responses and remarkably attenuated allergic airway inflammation in mice.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"15 1","pages":"481"},"PeriodicalIF":7.1,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11657170/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142855425","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}