Stem Cells International最新文献

{"title":"Immunoregulation of Quercetin and Kynurenic Acid on Human Umbilical Cord Mesenchymal Stem Cells Through Gene Expression of Aryl Hydrocarbon Receptor and Interleukin-6 in Hyperglycemic Milieu.","authors":"Thi Sam Nguyen, Thi Thuy Ngan Nguyen, Thi Phuong Anh Nguyen, Tran Bao Chau Ha, Manh Cuong Nguyen, Syed Shadab Raza, Vinh Truong Do, Hoang Ha Chu","doi":"10.1155/sci/6612312","DOIUrl":"10.1155/sci/6612312","url":null,"abstract":"<p><p>Mesenchymal stem cells (MSCs) exhibit great promise for treatment applications because of their immunosuppressive properties. The aryl hydrocarbon receptor (AHR), which is a transcription factor that is activated via ligand, has a pivotal role in regulating the immune system and is involved in a range of immune-related disorders. However, hyperglycemia, the defining biochemical hallmark of diabetes, creates a chronically pro-inflammatory microenvironment that impairs the immunoregulatory effects of MSCs. In this study, we explored the potential of kynurenic acid (KYNA) and quercetin, two naturally derived compounds, to modulate the immune response of MSCs through the regulation of AHR signaling under hyperglycemic conditions. We assessed the immunophenotyping and differentiation capacity of cultured human umbilical cord mesenchymal stem cells (hUC-MSCs) in a high-glucose medium and quantified the mRNA expression rate of <i>AHR</i>, <i>CYP1A1</i>, <i>CYP1B1</i>, and <i>IL-6</i> using real time PCR. Our study is the first to reveal that KYNA and quercetin enhance mRNA expression levels of <i>AHR</i> and <i>CYP1B1</i>, while reducing <i>IL-6</i> expression in hUC-MSCs, suggesting their potential as immunomodulators. These findings highlight the compounds' promise as drug candidates for immune-mediated diseases through stem cell therapy, particularly due to their modulation of AHR.</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2025 ","pages":"6612312"},"PeriodicalIF":3.8,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12228572/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144576252","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":"Isolate Circulating Mesenchymal Stromal Cells Without Growth Factor Administration and Using Density Gradient.","authors":"Jason Ma, Chung-Chuan Hsiung, Tzu-Hsien Yang, Hsiu-Yen Sun, Ming-Ling Kuo","doi":"10.1155/sci/5545892","DOIUrl":"10.1155/sci/5545892","url":null,"abstract":"<p><p>Mesenchymal stromal cells (MSCs) are recognized for their differentiation and immune regulation capabilities, which enhance their potential for treating various diseases. MSCs can be sourced from diverse tissues, with peripheral blood (PB) serving as a viable alternative to bone marrow. We now present an alternative strategy that eliminates the need for preadministering growth factors, utilizing density gradient methods, and culturing target cells in medium supplemented with autologous serum. PB was collected through venipuncture and then coincubated with glycerin. After incubation, a thin layer of cells above the red blood cells (RBCs) was isolated, showing an increased population of CD34^-CD45^- cells compared to PB mononuclear cell (PBMC) isolation using Ficoll gradient. After culture, adherent spindle-shaped cells were identified and collected to assess MSC surface markers, demonstrating their differentiation potential into adipocytes, osteocytes, and chondrocytes, thus, fulfilling the criteria for MSCs. The population doubling time (PDT) of isolated PB-MSCs was approximately 30-40 h in early passages. These PB-MSCs also exhibited immunomodulatory functions and are capable of suppressing T cell activation. We believe this protocol supports PB as a convenient alternative source for MSC isolation and offers new strategies for acquiring and maintaining PB-MSCs.</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2025 ","pages":"5545892"},"PeriodicalIF":3.8,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12202064/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144508351","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":"Human Muscle-Derived Vascular Stem Cells Can Support Hematopoietic Stem/Progenitor Cells In Vitro.","authors":"Tingting Yang, Jie Ma, Siqi Zhang, Rui Zhou, Xiaoping Yang, Bo Zheng","doi":"10.1155/sci/4451561","DOIUrl":"10.1155/sci/4451561","url":null,"abstract":"&lt;p&gt;&lt;p&gt;&lt;b&gt;Background:&lt;/b&gt; The normal hematopoiesis of the body depends on the interaction between hematopoietic stem/progenitor cells (HSPCs) and mesenchymal stem cells (MSCs) that support the growth and development of hematopoietic cells. However, the separation of MSCs from bone marrow is somewhat limited, and the researchers have turned their attention to stromal cells outside the bone marrow. As the largest organ of human body, skeletal muscle tissue stores a variety of muscle-derived vascular stem/progenitor cells, including muscle-derived pericytes/perivascular cells (MD-PCs) and skeletal muscle derived myoendothelial cells (MECs). Studies have shown that MD-PCs and MECs are similar to bone morrow-derived MSCs (BM-MSCs), which express the surface markers of MSCs and have the potential of multidirectional differentiation. However, very few researches have been done on whether MD-PCs and MECs, like MSCs, can support HSPCs expansion/proliferation, differentiation and possible hematopoietic regulation mechanisms, so the hematopoietic support of these cells remains to be studied. &lt;b&gt;Objective:&lt;/b&gt; To identify the biological characteristics of CD146&lt;sup&gt;+&lt;/sup&gt; PCs and MECs isolated from human skeletal muscle and to study their supporting effect on umbilical cord blood (UCB) CD34&lt;sup&gt;+&lt;/sup&gt; cells in vitro. &lt;b&gt;Methods:&lt;/b&gt; Human skeletal muscle-derived CD146&lt;sup&gt;+&lt;/sup&gt; PCs and MECs were isolated and purified by multiparameter flow cytometry and their biological characteristics were identified. The coculture system for CD34&lt;sup&gt;+&lt;/sup&gt; cells with CD146&lt;sup&gt;+&lt;/sup&gt; PCs and MECs as trophoblastic layer, and BM-MSCs as positive control, was established in vitro, respectively. The main outcome measures, including the number and immunophenotype of the cells, the colony formation ability, the expression levels of cytokines were analyzed and compared at 1, 2, and 4 weeks after coculture. &lt;b&gt;Results:&lt;/b&gt; CD146&lt;sup&gt;+&lt;/sup&gt; PCs and MECs were isolated by multiparameter flow cytometry and their purity of was 92.55% ± 0.55% and 96.60% ± 1.14% (&lt;i&gt;n&lt;/i&gt; = 18), respectively. Both of the cells could be differentiated into osteoblasts, chondrocytes, adipocytes, and myocytes. Compared with the positive control group of BM-MSCs, the experimental group of CD146&lt;sup&gt;+&lt;/sup&gt; PCs and MECs showed no significant differences in cell number, colony formation ability and immunophenotype (CD45&lt;sup&gt;+&lt;/sup&gt;, CD34&lt;sup&gt;+&lt;/sup&gt; CD33&lt;sup&gt;-&lt;/sup&gt;, CD14&lt;sup&gt;+&lt;/sup&gt;, and CD10&lt;sup&gt;+&lt;/sup&gt;/CD19&lt;sup&gt;+&lt;/sup&gt;; &lt;i&gt;p&lt;/i&gt;  &gt; 0.05, &lt;i&gt;n&lt;/i&gt; = 5), separately. The expression levels of cytokines in the culture supernatants of CD146&lt;sup&gt;+&lt;/sup&gt; PCs group, MECs group, and BM-MSCs group were measured by ELISA. The expression levels of TPO, IFN-γ, HGF, MCSF, and SCF cytokines were different among CD146&lt;sup&gt;+&lt;/sup&gt; PCs, MECs, and human BM-MSCs (&lt;i&gt;p&lt;/i&gt; &lt; 0.05, &lt;i&gt;n&lt;/i&gt; = 3). Due to the no nourishing feeder layer in culture system, the number of CD34&lt;sup&gt;+&lt;/sup&gt; cells decreased significantly in the 1st","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2025 ","pages":"4451561"},"PeriodicalIF":3.8,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12187439/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144485704","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":"Safety and Effectiveness of Muse Cell Transplantation in a Large-Animal Model of Hepatic Fibrosis.","authors":"Taketo Nishina, Hiroaki Haga, Shohei Wakao, Keita Maki, Kei Mizuno, Tomohiro Katsumi, Kyoko Tomita Hoshikawa, Takafumi Saito, Masahiro Iseki, Michiaki Unno, Mari Dezawa, Yoshiyuki Ueno","doi":"10.1155/sci/6699571","DOIUrl":"10.1155/sci/6699571","url":null,"abstract":"<p><p><b>Background:</b> In recent years, liver regeneration therapy using mesenchymal stem cells (MSC) has been investigated as an alternative therapy for end-stage liver diseases. Among these MSCs, multilineage-differentiating stress enduring (Muse) cells are reported to be effective in mouse models. The present study investigated the safety and effectiveness of Muse cell transplantation in large animal models of hepatic fibrosis. <b>Methods:</b> Muse cells and MSC were prepared from bone marrow cells of male mini pigs (Göttingen strain). Recipients mini pigs (female Göttingen strain) were repeatedly administered with carbon tetrachloride (CCl₄) intraperitoneally for 12 weeks to induce liver fibrosis. Thereafter, either Muse cells or MSCs were transplanted intravenously. After the cell transplantation, laboratory tests, vital signs, and liver histology were evaluated (Muse cell group (<i>n</i> = 6), MSC group (<i>n</i> = 6), and vehicle group (<i>n</i> = 7)). <b>Results:</b> Liver fibrogenesis was successfully induced after 12 weeks of CCl₄ administration. Engraftment of transplanted cells and differentiation into hepatocytes were confirmed in recipients' liver. In Muse cell group, significant increase of serum albumin (Alb) level was observed at 4 weeks compared to those of control groups (<i>p</i>  < 0.05). Hepatic proliferating cell nuclear antigen (PCNA) positive cells were significantly increased in the Muse cell group (<i>p</i>  < 0.05). Hepatic fibrogenesis at 12 weeks after transplantation were significantly improved in Muse cell group (<i>p</i>  < 0.05). Alpha-smooth muscle actin (α-SMA) immunostaining revealed significant decrease in liver from Muse cell transplanted recipients. No serious adverse effects were observed. <b>Conclusions:</b> Muse cell transplantation was safe and effective in large animal models of hepatic fibrosis. The positive effects were observed in namely 4 weeks after transplantation. Since biochemical as well as histological improvements were demonstrated, future studies including establishing ideal administration protocol seem to be feasible as a preclinical study.</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2025 ","pages":"6699571"},"PeriodicalIF":3.8,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12181669/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144476684","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":"miR-1275 Delivered via Mesenchymal Stem Cell-Derived Extracellular Vesicles Regulates ER-Phagy Through AXIN2 in Nucleus Pulposus Cells.","authors":"Zhiwu Dong, Hailong Zhang, Wenwei Yang, Keliang Huang, Xin Zhang, Lianxiang Xing, Ying Zhang, Kewen Zhao","doi":"10.1155/sci/5091529","DOIUrl":"10.1155/sci/5091529","url":null,"abstract":"<p><p>Intervertebral disc degeneration (IDD) is a major contributor to low back pain, a prevalent and debilitating condition. Nucleus pulposus (NP) cells are essential for maintaining disc homeostasis, and their dysfunction plays a crucial role in IDD development. This study aimed to explore the potential role of miR-1275, delivered via mesenchymal stem cell-derived extracellular vesicles (MSCs-EVs), in IDD pathogenesis and to elucidate the underlying molecular mechanisms through <i>in vitro</i> investigations. Decreased miR-1275 expression and elevated endoplasmic reticulum (ER) stress were observed in degenerated human NP tissues compared to normal controls. An <i>in vitro</i> IDD model was established by treating NP cells (NPCs) with advanced glycation end products (AGEs). Subsequent experiments demonstrated that EVs from miR-1275-overexpressing MSCs reduced AGE-induced ER stress, extracellular matrix (ECM) degradation, and apoptosis in NPCs by enhancing ER-phagy. Bioinformatic analyses identified AXIN2 as a direct target of miR-1275. Remarkably, AXIN2 overexpression significantly attenuated the effects of miR-1275 on NPC proliferation, apoptosis, ER stress, and ER-phagy under AGE-induced conditions. Mechanistic studies validated AXIN2 as a target of miR-1275, with miR-1275 binding to the 3' untranslated region of AXIN2 and regulating its expression. Collectively, our <i>in vitro</i> findings reveal that MSCs-EVs carrying miR-1275 can modulate ER stress and enhance ER-phagy in NPCs through the targeted downregulation of AXIN2, suggesting a potential molecular mechanism in IDD pathogenesis.</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2025 ","pages":"5091529"},"PeriodicalIF":3.8,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12140824/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144235288","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":"Transcription Factor SOX10 Improves Migration and Homing of MSCs After Myocardial Infarction by Upregulating CXCR4.","authors":"Baoping Deng, Qili Liu, Jiemin Yang, Jing Xu, Hongmei Zheng, Weiping Deng","doi":"10.1155/sci/1880402","DOIUrl":"10.1155/sci/1880402","url":null,"abstract":"<p><p><b>Background:</b> CXCR4 enhances the homing of mesenchymal stem cells (MSCs), thereby potentially improving outcomes in myocardial infarction (MI). However, the molecular mechanisms underlying MSC homing remain poorly understood. <b>Methods:</b> The identity of MSCs was confirmed through flow cytometry, utilizing their cluster of differentiation (CD) marker profile. Migration and invasion were assessed using wound healing and transwell assays. In a rat MI model, myocardial function, hemodynamic parameters, and the degree of myocardial fiber damage were evaluated post-MSC treatment, along with the observation of MSC homing. Luciferase assays identified binding sites between SOX10 and the CXCR4 promoter, and the effects of SOX10 on MSC migration, invasion, and homing were explored both <i>in vitro</i> and <i>in vivo</i>. <b>Results:</b> Overexpression of CXCR4 significantly enhanced MSC migration, invasion, and homing. MSCs overexpressing CXCR4 improved cardiac function and reduced infarct size in the rat MI model. A direct interaction between SOX10 and CXCR4 was confirmed, with SOX10 acting as a transcription factor to upregulate CXCR4 expression, thereby enhancing MSC homing and ameliorating MI in rats. Knockdown of SOX10 reversed the beneficial effects of CXCR4-overexpressing MSCs on MI therapy, as well as the functional impact of CXCR4 on MSCs. <b>Conclusion:</b> In conclusion, SOX10 facilitates MSC homing by upregulating CXCR4 expression, offering a potential therapeutic approach for MI treatment.</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2025 ","pages":"1880402"},"PeriodicalIF":3.8,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12129602/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144209555","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":"Mixtures of PRR Ligands Partly Mimic the Immunomodulatory Response of <i>γ</i>i <i>Staphylococcus aureus</i>, Enhancing Osteogenic Differentiation of Human Mesenchymal Stromal Cells.","authors":"Paree Khokhani, Kelly Warmink, Moyo Kruyt, Harrie Weinans, Debby Gawlitta","doi":"10.1155/sci/1445520","DOIUrl":"10.1155/sci/1445520","url":null,"abstract":"<p><p>Recent evidence indicates the potential of gamma-irradiated (<i>γ</i>i) <i>Staphylococcus aureus</i> to be used as an osteo-immunomodulator for bone regeneration. This study aims at characterizing the inflammatory milieu caused by the stimulation of <i>γ</i>i <i>S. aureus</i> in immune cells and investigates its effects on MSC osteogenic differentiation. Furthermore, we aimed to recreate the immune-modulatory response exhibited by <i>γ</i>i <i>S. aureus</i> by using a mixture of various synthetic pathogen recognition receptor (PRR) ligands consisting of TLR2, TLR8, TLR9, and NOD2 agonists. Human peripheral blood mononuclear cells (hPBMCs), isolated from healthy human donors, were exposed to <i>γ</i>i <i>S. aureus</i> or seven different ligand mixtures. After 24 h, the conditioned medium (CM) from the hPBMCs was collected and its effects on hMSC osteogenic differentiation were investigated by assessing alkaline phosphatase (ALP) activity and matrix mineralization. The hPBMCs and their CM were also analyzed by bulk RNA sequencing and for cytokine secretion. CM from the <i>γ</i>i <i>S. aureus</i> and the mixture consisting of Pam3CSK4, C-class CpG oligodeoxynucleotide (CpG ODN C), and murabutide targeting TLR2, TLR9, and NOD2 showed a fivefold increase in ALP and matrix mineralization in a donor-dependent manner. These effects were due to the upregulation of inflammatory signaling pathways, which led to an increase in cytokines and chemokines TNF, interleukin (IL)-6, IFN-<i>γ</i>, IL-1<i>α</i>, CXCL10, CCL18, CCL17, CXCL1, and CCL5. Upregulation of genes like BMP2R, BMP6R, BGLAP, and others contributed to the upregulation of osteogenic pathways in the hPBMCs stimulated with <i>γ</i>i <i>S. aureus</i> and the aforementioned mix. Thus, formulations with mixtures of PRR ligands may serve as immune-modulatory osteogenesis-enhancing agents.</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2025 ","pages":"1445520"},"PeriodicalIF":3.8,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12127128/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144209554","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":"Overexpression of Decorin Optimizes the Treatment Efficacy of Umbilical Cord Mesenchymal Stem Cells in Bleomycin-Induced Pulmonary Fibrosis in Rats.","authors":"Yaofeng Zhi, Minghui Shu, Pingsheng Tang, Yingjie Li, Min Guo, Jiongrui Deng, Haixin Mo, Meimei Wu, Baoyi Liu, Yanyang Mai, Jie Ling, Xulin Zhao, Xin Zhang, Wanli Zuo","doi":"10.1155/sci/6324980","DOIUrl":"10.1155/sci/6324980","url":null,"abstract":"<p><p>Idiopathic pulmonary fibrosis (IPF) is a long-term, diffuse pulmonary parenchyma lesion that primarily affects middle-aged and older adults. It is characterized by pulmonary interstitial fibrosis of unknown cause. The death rate upon diagnosis is higher than that of many other cancer types. Mesenchymal stem cell (MSC) treatment of organ fibrosis is a hot topic in preclinical and clinical research because it effectively treats IPF. In recent years, decorin (DCN) has been regarded as a critical mediator for its anti-inflammatory and antifibrotic effects. The purpose of this study was to generate human umbilical cord MSCs (HUC-MSCs) that overexpress DCN and to investigate the safety, mechanism, and effectiveness of using these cells to cure pulmonary fibrosis caused by bleomycin (BLM). First, lentiviral (LV) particles carrying the therapeutic DCN gene (LV-DCN) and control LV particles were created and transfected using the plasmid vector GV208 to create a viral solution for infecting HUC-MSCs. These solutions were used to create a DCN overexpression cell line and an MSC-Con. cell line infected with the control lentivirus. Intratracheal injection of BLM was used to establish a rat model of pulmonary fibrosis. On the second day following modeling, different treatments were administered, and the body weight and survival status of the rats were noted. The relevant tests were performed on days 15 and 29 following modeling. The results demonstrated that the overexpression of DCN did not affect the properties of HUC-MSCs and that these cells were effective in treating IPF. MSC-Con. and MSC-DCN reduced systemic inflammation by reducing serum interleukin (IL) 1<i>β</i>. Both cell types successfully treated pulmonary fibrosis in rats, as demonstrated by hematoxylin and eosin (HE) and Masson staining. MSC-DCN showed better efficacy due to lower mortality, higher weight gain, less alveolar inflammation, and less fibrosis. The safety of venous transplantation with MSCs was established by HE staining of the heart, liver, spleen, and kidney, as well as serum lactate dehydrogenase (LDH), creatinine (CRE), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) levels. Immunohistochemical (IHC) staining of CD68 and CD206 in lung tissue and in vitro experiments on THP-1-induced M2 macrophage polarization and transforming growth factor-beta 1 (TGF-<i>β</i>1)-induced MRC-5 fibrosis indicated that MSC-DCN may mitigate lung inflammation by altering macrophage recruitment and polarization and inhibiting TGF-<i>β</i>1 expression to reduce fibrous hyperplasia and collagen deposition, thereby improving the treatment of BLM-induced IPF.</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2025 ","pages":"6324980"},"PeriodicalIF":3.8,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12119169/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144175021","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":"Effects of Bariatric Surgery-Related Weight Loss on the Characteristics, Metabolism, and Immunomodulation of Adipose Stromal/Stem Cells in a Follow-Up Study.","authors":"Amna Adnan, Miia Juntunen, Tuula Tyrväinen, Minna Kelloniemi, Laura Kummola, Reija Autio, Mimmi Patrikoski, Susanna Miettinen","doi":"10.1155/sci/1212255","DOIUrl":"10.1155/sci/1212255","url":null,"abstract":"<p><p><b>Background:</b> The success of adipose stromal/stem cell (ASC)-based therapies may depend on donor characteristics such as body mass index (BMI). A high BMI may negatively impact the therapeutic potential of ASCs, but the effects of weight loss on ASC-mediated immunoregulation have not been extensively studied. <b>Methods:</b> ASCs were obtained from donors with obesity (obASCs) undergoing bariatric surgery and from the same donors after weight loss (wlASCs). Plasma samples, adipose tissue histology, and ASC characteristics, such as mitochondrial respiration and inflammatory factors, were studied before and after weight loss. The immunomodulatory capacity of ob/wlASCs was evaluated in cocultures with prepolarized and preactivated proinflammatory (M1) and anti-inflammatory (M2) macrophages by determining macrophage surface markers, gene expression, and cytokine secretion. <b>Results:</b> Weight loss significantly decreased plasma leptin levels and increased adiponectin levels. After weight loss, crown-like structures (CLSs) were undetectable, and the adipocyte size decreased. Weight loss significantly improved mitochondrial respiration in ASCs and resulted in a notable increase in their proliferative capacity. The proinflammatory marker genes tumor necrosis factor alpha (<i>TNF-α</i>), chemokine ligand 5 (<i>CCL5</i>), and cyclooxygenase-2 (<i>COX2</i>), as well as the proinflammatory cytokine interleukin 12p70 (IL-12p70), were significantly downregulated, while the anti-inflammatory gene tumor necrosis factor-inducible gene 6 (<i>TSG6</i>) was also significantly downregulated in ASC monocultures after weight loss. Following weight loss, ASCs exhibited increased proinflammatory properties when cocultured with macrophages, characterized by the downregulation of anti-inflammatory factors, along with the upregulation of several proinflammatory factors, compared with the effects of macrophage monocultures. Conversely, wlASCs demonstrated improved immunosuppressive functions in coculture with macrophages, as indicated by the upregulation of <i>TSG6</i> gene expression and interleukin 4 (IL-4) secretion. <b>Conclusions:</b> Weight loss improved donors' metabolic health and partially recovered ASCs' anti-inflammatory gene expression and cytokine secretion profiles in monocultures. However, it was inadequate to fully restore the immunosuppressive functions of ASCs in cocultures with macrophages. Therefore, not only donor BMI but also weight loss history, among other donor characteristics, might be considered for optimal ASC-based therapy.</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2025 ","pages":"1212255"},"PeriodicalIF":3.8,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12092157/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144111858","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":"Spatio-Temporal Regulation of IGFs in Enamel Development: Molecular Mechanisms From Ameloblast Polarity to Mineralization Homeostasis.","authors":"Xue Zeng, Pengcheng He","doi":"10.1155/sci/9665706","DOIUrl":"10.1155/sci/9665706","url":null,"abstract":"<p><p>The development of enamel relies on the precise regulation of ameloblast differentiation, enamel matrix secretion, and mineralization. The formation of enamel is crucial for the normal function of dental tissues, and promoting enamel remineralization is of significant importance for the treatment of dental caries. Understanding the underlying mechanisms of enamel development is essential for oral therapy and provides a bridge to tooth regeneration. Among various growth factors, the insulin-like growth factor (IGF) family, including IGF-1 and IGF-2, has been shown to play a key role in enamel formation by activating signaling pathways such as PI3K/AKT and MAPK. This review summarizes the role of the IGF family in tooth development and enamel formation and sheds light on key parts of the research for future treatment improvements.</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2025 ","pages":"9665706"},"PeriodicalIF":3.8,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12092154/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144111910","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}