Stem Cell Research & Therapy最新文献

{"title":"FDFT1 maintains glioblastoma stem cells through activation of the Akt pathway.","authors":"Hui Mo, Jiajia Shao, Zhun Li, Peiting Zeng, Xinke Yin, Yongsheng Huang, Peng Wang, Jianwei Liao","doi":"10.1186/s13287-024-04102-7","DOIUrl":"10.1186/s13287-024-04102-7","url":null,"abstract":"<p><strong>Background: </strong>Cancer stem cells (CSCs) have unique metabolic characteristics and are hypothesized to contribute significantly to the recurrence and drug resistance of glioblastoma multiforme (GBM). However, the reliance on mitochondrial metabolism and the underlying mechanism of glioblastoma stem cells (GSCs) remains to be elucidated.</p><p><strong>Methods: </strong>To quantify differential mitochondrial protein expression between GSCs and differentiated cells, a mass spectrum screen was applied by the Stable Isotope Labeling with Amino Acids in Cell Culture (SILAC) technique. Functional experiments including CCK8, neurosphere formation, flow cytometry, transwell, and wound healing assays were conducted to evaluate GBM cell malignant phenotype. The potential molecular mechanism of FDFT1 was screened by RNA-seq analyses. The candidate target genes were validated through RT-qPCR and western blot analyses.</p><p><strong>Results: </strong>As a top candidate, FDFT1 protein expression in GSCs was elevated relative to their differentiated counterparts. Functionally, the knockdown of FDFT1 suppressed the GBM cell proliferation and migration, while simultaneously enhancing sensitivity to temozolomide. Treatment with both the FDFT1 inhibitor (YM-53601) and simvastatin (an HMG-CoA reductase inhibitor) induced apoptosis in GSCs. Mechanistically, FDFT1 was transcriptionally regulated by SREBP2 but not SREBP1. Furthermore, FDFT1 activates the AKT pathway to regulate tumor metabolism and maintain the stemness of tumor cells.</p><p><strong>Conclusions: </strong>GSCs exhibit a dependency on FDFT1-mediated mevalonate metabolism. Inhibition of FDFT1 could represent a potent strategy to eliminate GSCs.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"15 1","pages":"492"},"PeriodicalIF":7.1,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11662426/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872625","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":"World's first: stem cell therapy reverses diabetes.","authors":"Dinesh Kumar, Rajni Tanwar","doi":"10.1186/s13287-024-04036-0","DOIUrl":"10.1186/s13287-024-04036-0","url":null,"abstract":"","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"15 1","pages":"487"},"PeriodicalIF":7.1,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11662597/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872769","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":"Small extracellular vesicles derived from umbilical cord mesenchymal stem cells alleviate radiation-induced cardiac organoid injury.","authors":"Hu Cao, Liang Yue, Jingyuan Shao, Fanxuan Kong, Shenghua Liu, Hongyu Huai, Zhichao He, Zhuang Mao, Yuefeng Yang, Yingxia Tan, Hua Wang","doi":"10.1186/s13287-024-04115-2","DOIUrl":"10.1186/s13287-024-04115-2","url":null,"abstract":"<p><strong>Background: </strong>Radiation-induced heart disease (RIHD) is one of the most serious complications of radiation therapy (RT) for thoracic tumors, and new interventions are needed for its prevention and treatment. Small extracellular vesicles (sEVs) from stem cells have attracted much attention due to their ability to repair injury. However, the role of umbilical cord mesenchymal stem cell (UCMSC)-derived sEVs in protecting cardiac organoids from radiation-induced injury and the underlying mechanisms are largely unknown.</p><p><strong>Methods: </strong>A radiation-induced cardiac organoid injury model was established by using X-ray radiation, and the optimal radiation dose of 20 Gy was determined by live/dead staining. After radiation, the cardiac organoids were treated with sEVs derived from UCMSCs, and energy metabolism, calcium transient changes and the ultrastructure of the organoids were assessed through Seahorse analysis, optical mapping and transmission electron microscopy, respectively. Confocal microscopy was used to observe the changes in mitochondrial ROS and mitochondrial membrane potential (ΔΨm). Furthermore, real-time quantitative PCR was used to verify the RNA-seq results.</p><p><strong>Results: </strong>After X-ray radiation, the mortality of cardiac organoids significantly increased, energy metabolism decreased, and calcium transients changed. We also observed that the mitochondrial structure of cardiac organoids was disrupted and that ΔΨm was decreased. These effects could be inhibited by sEVs treatment. sEVs may protect against radiation-induced cardiac organoid injury by regulating oxidative phosphorylation and the p53 signaling pathway.</p><p><strong>Conclusion: </strong>sEVs derived from UCMSCs can be used as a potential therapeutic strategy for radiation-induced heart disease.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"15 1","pages":"493"},"PeriodicalIF":7.1,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11662859/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872767","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":"Near-infrared light induces neurogenesis and modulates anxiety-like behavior.","authors":"Xing Qi, Zhiliang Xu, Xingchen Liu, Yanan Ren, Yecheng Jin, Wenjie Sun, Jiangxia Li, Duo Liu, Shuwei Liu, Qiji Liu, Xi Li","doi":"10.1186/s13287-024-04114-3","DOIUrl":"10.1186/s13287-024-04114-3","url":null,"abstract":"<p><strong>Background: </strong>The hippocampus is associated with mood disorders, and the activation of quiescent neurogenesis has been linked to anxiolytic effects. Near-infrared (NIR) light has shown potential to improve learning and memory in human and animal models. Despite the vast amount of information regarding the effect of visible light, there is a significant gap in our understanding regarding the response of neural stem cells (NSCs) to NIR stimulation, particularly in anxiety-like behavior. The present study aimed to develop a new optical manipulation approach to stimulate hippocampal neurogenesis and understand the mechanisms underlying its anxiolytic effects.</p><p><strong>Methods: </strong>We used 940 nm NIR (40 Hz) light exposure to stimulate hippocampal stem cells in C57BL/6 mice. The enhanced proliferation and astrocyte differentiation of NIR-treated NSCs were assessed using 5-ethynyl-2'-deoxyuridine (EdU) incorporation and immunofluorescence assays. Additionally, we evaluated calcium activity of NIR light-treated astrocytes using GCaMP6f recording through fluorescence fiber photometry. The effects of NIR illumination of the hippocampus on anxiety-like behaviors were evaluated using elevated plus maze and open-field test.</p><p><strong>Results: </strong>NIR light effectively promoted NSC proliferation and astrocyte differentiation via the OPN4 photoreceptor. Furthermore, NIR stimulation significantly enhanced neurogenesis and calcium-dependent astrocytic activity. Moreover, activating hippocampal astrocytes with 40-Hz NIR light substantially improved anxiety-like behaviors in mice.</p><p><strong>Conclusions: </strong>We found that flickering NIR (940 nm/40Hz) light illumination improved neurogenesis in the hippocampus with anxiolytic effects. This innovative approach holds promise as a novel preventive treatment for depression.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"15 1","pages":"494"},"PeriodicalIF":7.1,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11662543/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872636","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 umbilical mesenchymal stem cells ameliorate atrophic gastritis in aging mice by participating in mitochondrial autophagy through Ndufs8 signaling.","authors":"Qiang Rui, Chuyu Li, Yiqi Rui, Chuanzhuo Zhang, Cunbing Xia, Qing Wang, Yuanyuan Liu, Peng Wang","doi":"10.1186/s13287-024-04094-4","DOIUrl":"10.1186/s13287-024-04094-4","url":null,"abstract":"<p><strong>Background: </strong>Chronic atrophic gastritis (CAG) is a chronic disease of the gastric mucosa characterized by a reduction or an absolute disappearance of the original gastric glands, possibly replaced by pseudopyloric fibrosis, intestinal metaplasia, or fibrosis. CAG develops progressively into intestinal epithelial metaplasia, dysplasia, and ultimately, gastric cancer. Epidemiological statistics have revealed a positive correlation between the incidence of CAG and age. Mesenchymal stem cells (MSCs) are a type of adult stem cells derived from mesoderm, with strong tissue repair capabilities. Therefore, the restoration of the gastric mucosa may serve as an efficacious strategy to ameliorate CAG and avert gastric cancer. However, the mechanisms by which MSCs inhibit the relentless progression of aging atrophic gastritis remain to be elucidated. This study endeavored to assess a novel approach utilizing MSCs to treat CAG and forestall carcinogenics.</p><p><strong>Methods: </strong>In this study, we selected mice with atrophic gastritis from naturally aging mice and administered human umbilical cord-derived mesenchymal stem cells (hUMSCs) via tail vein injection to evaluate the therapeutic effects of hUMSCs on age-related chronic atrophic gastritis. Initially, we employed methods such as ELISA, immunohistochemical analysis, and TUNEL assays to detect changes in the mice post-hUMSC injection. Proteomic and bioinformatics analyses were conducted to identify differentially expressed proteins, focusing on NADH: ubiquinone oxidoreductase core subunit S8 (Ndufs8). Co-culturing hUMSCs with Ndufs8 knockout gastric mucosal epithelial cells (GMECs), we utilized flow cytometry, Western blotting, real-time quantitative PCR, and immunofluorescence to investigate the mechanisms of action of hUMSCs.</p><p><strong>Results: </strong>We observed that hUMSCs are capable of migrating to and repairing damaged gastric mucosa. Initially, hUMSCs significantly enhanced the secretion of gastric proteins PG-1 and G17, while concurrently reducing inflammatory cytokines. Furthermore, hUMSCs mitigated gastric fibrosis and apoptosis in mucosal cells. Proteomic and bioinformatic analyses revealed alterations in the protein network involved in mitochondrial autophagy, with Ndufs8 playing a pivotal role. Upon knocking out Ndufs8 in GMECs, we noted mitochondrial damage and reduced autophagy, leading to an aged phenotype in GMECs. Co-culturing Ndufs8-knockout GMECs with hUMSCs demonstrated that hUMSCs could ameliorate mitochondrial dysfunction and restore the cell cycle in GMECs.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"15 1","pages":"491"},"PeriodicalIF":7.1,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11662822/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872587","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":"Impact of photobiomodulation on neural embryoid body formation from immortalized adipose-derived stem cells.","authors":"Precious Earldom Mulaudzi, Heidi Abrahamse, Anine Crous","doi":"10.1186/s13287-024-04088-2","DOIUrl":"10.1186/s13287-024-04088-2","url":null,"abstract":"<p><strong>Background: </strong>Embryoid bodies (EBs) are three-dimensional (3D) multicellular cell aggregates that are derived from stem cell and play a pivotal role in regenerative medicine. They recapitulate many crucial aspects of the early stages of embryonic development and is the first step in the generation of various types of stem cells, including neuronal stem cells. Current methodologies for differentiating stem cells into neural embryoid bodies (NEBs) in vitro have advanced significantly, but they still have limitations which necessitate improvement. Photobiomodulation (PBM) a low powered light therapy is a non-invasive technique shown to promote stem cell proliferation and differentiation.</p><p><strong>Methods: </strong>This in vitro study elucidated the effects of photobiomodulation (PBM) on the differentiation of immortalized adipose-derived stem cells (iADSCs) into NEBs within a 3D cell culture environment. The study utilized PBM at wavelengths of 825 nm, 525 nm, and a combination of both, with fluences of 5 and 10 J/cm². Morphology, viability, metabolic activity, and differentiation following PBM treatment was analysed.</p><p><strong>Results: </strong>The results revealed that the effects of photobiomodulation (PBM) are dose dependent. PBM, at 825 nm with a fluence of 10 J/cm², significantly enhanced the size of neural embryoid bodies (NEBs), improved cell viability and proliferation, and reduced lactate dehydrogenase (LDH) levels, indicating minimal cell damage. Interestingly, the stem cell marker CD 44 was upregulated at 5 J/cm² in all treatment groups at 24 and 96 hpi, CD105 increased with 825 nm at 10 J/cm² at 24 hpi, which may be attributed to a heterogeneous cell population within the NEBs. Pax6 expression showed transient activation. Nestin was upregulated at 825 nm with 10 J/cm² at 96 hpi, suggesting a promotion of neural precursor populations. GFAP an intermediate filament protein was upregulated at 825 nm at 10 J/cm2 at both 24 and 96 hpi. SOX2, a pluripotency marker, was expressed at 5 J/cm² across all wavelengths. Neu N a neuronal nuclei marker was expressed at 5 J/cm² in all treatments at 24 hpi and over time the expression was observed in all treatment groups at 10 J/cm².</p><p><strong>Conclusion: </strong>In conclusion, the application of PBM at 825 nm with a fluence of 10 J/cm² during the differentiation of iADSCs into NEBs resulted in optimal differentiation. Notably, the neuronal marker Nestin was significantly upregulated, highlighting the potential of the PBM approach for enhancing neuronal differentiation its promising applications in regenerative medicine.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"15 1","pages":"489"},"PeriodicalIF":7.1,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11662703/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872594","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 neural stem cells directly programmed from peripheral blood show functional integration into the adult mouse brain.","authors":"Lea Jessica Berg, Chung Ku Lee, Hideaki Matsumura, Anke Leinhaas, Rachel Konang, Ali H Shaib, Pedro Royero, Julia Schlee, Chao Sheng, Heinz Beck, Martin Karl Schwarz, Nils Brose, Jeong Seop Rhee, Oliver Brüstle","doi":"10.1186/s13287-024-04110-7","DOIUrl":"10.1186/s13287-024-04110-7","url":null,"abstract":"<p><p>Transplantation of induced pluripotent stem cell-derived neural cells represents a promising strategy for treating neurodegenerative diseases. However, reprogramming of somatic cells and their subsequent neural differentiation is complex and time-consuming, thereby impeding autologous applications. Recently, direct transcription factor-based conversion of blood cells into induced neural stem cells (iNSCs) has emerged as a potential alternative. However, little is known about the functionality of iNSC-derived neurons upon in vivo transplantation. Here, we grafted human iNSCs derived from adult peripheral blood by temporary overexpression of the transcription factors SOX2 and cMYC into the hippocampus or striatum of adult unlesioned immunodeficient Rag2^tm1FwaIl2rg^tm1Wjl mice of both sexes. Engrafted cells gave rise to stable transplants composed of mature neurons displaying extensive neurite outgrowth and dendritic spine formation. Functional analyses of acute slices using patch clamp recordings revealed that already after 12 weeks of in vivo maturation, most of iNSC-derived cells possess unique properties exclusive to neurons and exhibit voltage-dependent ion channel currents as well as action potential firing. Moreover, the formation of spontaneous inhibitory and excitatory postsynaptic currents, along with Rabies virus-based retrograde monosynaptic tracing data, strongly supports the structural and functional integration of graft-derived neurons. Taken together, our data demonstrate that iNSCs directly derived from peripheral blood cells have the inherent capacity to achieve full functional maturation in vivo, qualifying them as an alternative potential donor source for restorative applications and deserving further investigation.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"15 1","pages":"488"},"PeriodicalIF":7.1,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11662720/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872654","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":"Matrix-free human lung organoids derived from induced pluripotent stem cells to model lung injury.","authors":"Bettina Budeus, Chiara Kroepel, Lisa Marie Stasch, Diana Klein","doi":"10.1186/s13287-024-04106-3","DOIUrl":"10.1186/s13287-024-04106-3","url":null,"abstract":"<p><strong>Background: </strong>Organoids, as near-physiological 3D culture systems, offer new opportunities to study the pathogenesis of various organs in mimicking the cellular complexity and functionality of human organs.</p><p><strong>Method: </strong>Here we used a quite simple and very practicable method to successfully generate induced pluripotent stem cell (iPSC)-derived human lung organoids (LuOrg) in a matrix-free manner as an alternative to the widely used preclinical mouse models in order to investigate normal lung damage in detail and as close as possible to the patient. We performed detailed morphological and molecular analyses, including bulk and single cell RNA sequencing, of generated lung organoids and evaluated the quality and robustness of our model as a potential in vitro platform for lung diseases, namely radiation-induced lung injury.</p><p><strong>Results: </strong>A matrix-free method for differentiation of iPSCs can be used to obtain lung organoids that morphologically reflect the target tissue of the human lung very well, especially with regard to the cellular composition. The different cellular fates were investigated following the genotoxic stress induced by radiation and revealed further insights in the radiation-sensitivity of the different lung cells. Finally, we provide cellular gene sets found to be induced in the different lung organoid cellular subsets after irradiation, which could be used as additional RT response and particularly senescence gene sets in future studies.</p><p><strong>Conclusion: </strong>By establishing these free-floating LuOrgs for the investigation of cancer therapeutic approaches as a new and patient-oriented in vitro platform particularly in experimental radiooncology, not only a reduction in the number of experimental animals, but also an adequately and meaningfully replacement of corresponding animal experiments can be achieved.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"15 1","pages":"468"},"PeriodicalIF":7.1,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11657174/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142854759","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":"Multiomics analyses reveal adipose-derived stem cells inhibit the inflammatory response of M1-like macrophages through secreting lactate.","authors":"Tetsuhiro Horie, Hiroaki Hirata, Takuya Sakamoto, Hironori Kitajima, Atsushi Fuku, Yuka Nakamura, Yumi Sunatani, Ikuhiro Tanida, Hiroshi Sunami, Yoshiyuki Tachi, Yasuhito Ishigaki, Naoki Yamamoto, Yusuke Shimizu, Toru Ichiseki, Ayumi Kaneuji, Kuniyoshi Iwabuchi, Satoshi Osawa, Norio Kawahara","doi":"10.1186/s13287-024-04072-w","DOIUrl":"10.1186/s13287-024-04072-w","url":null,"abstract":"<p><strong>Background: </strong>Adipose-derived stem cells (ADSCs) are widely used in the field of regenerative medicine because of their various functions, including anti-inflammatory effects. ADSCs are considered to exert their anti-inflammatory effects by secreting anti-inflammatory cytokines and extracellular vesicles. Although recent studies have reported that metabolites have a variety of physiological activities, whether those secreted by ADSCs have anti-inflammatory properties remains unclear. Here, we performed multiomics analyses to examine the effect of ADSC-derived metabolites on M1-like macrophages, which play an important role in inflammatory responses.</p><p><strong>Methods: </strong>The concentration of metabolites in the culture supernatant of ADSCs was quantified using capillary electrophoresis time-of-flight mass spectrometry. To evaluate their effects on inflammatory responses, M1-like macrophages were exposed to the conditioned ADSC medium or their metabolites, and RNA sequencing was used to detect gene expression changes. Immunoblotting was performed to examine how the metabolite suppresses inflammatory processes. To clarify the contribution of the metabolite in the conditioned medium to its anti-inflammatory effects, metabolite uptake was pharmacologically inhibited, and gene expression and the tumor necrosis factor-α concentration were measured by quantitative PCR and enzyme-linked immunosorbent assay, respectively.</p><p><strong>Results: </strong>Metabolomic analysis showed large amounts of lactate in the culture supernatant. The conditioned medium and lactate significantly suppressed or increased the pro-inflammatory and anti-inflammatory gene expressions. However, sequencing and immunoblotting analysis revealed that lactate did not induce polarization from M1- to M2-like macrophages. Based on a recent report that the immunosuppressive effect of lactate depends on epigenetic reprogramming, histone acetylation was investigated, and H3K27ac expression was upregulated. In addition, 7ACC2, which specifically inhibits the monocarboxylate transporter 1, significantly inhibited the anti-inflammatory effect of the conditioned ADSC medium on M1-like macrophages.</p><p><strong>Conclusions: </strong>Our results showed that ADSCs suppress pro-inflammatory effects of M1-like macrophages by secreting lactate. This study adds to our understanding of the importance of metabolites and is also expected to elucidate new mechanisms of ADSC treatments.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"15 1","pages":"485"},"PeriodicalIF":7.1,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11657992/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142855220","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":"FAM96B negatively regulates FOSL1 to modulate the osteogenic differentiation and regeneration of periodontal ligament stem cells via ferroptosis.","authors":"Qianyi Qin, Haoqing Yang, Runzhi Guo, Yunfei Zheng, Yiping Huang, Luyuan Jin, Zhipeng Fan, Weiran Li","doi":"10.1186/s13287-024-04083-7","DOIUrl":"10.1186/s13287-024-04083-7","url":null,"abstract":"<p><strong>Background: </strong>Periodontal ligament stem cell (PDLSC)-based therapy is one of the methods to assist bone regeneration. Understanding the functional regulation of PDLSCs and the mechanisms involved is a crucial issue in bone regeneration. This study aimed to explore the roles of the family with sequence similarity 96 member B (FAM96B) in the functional regulation of PDLSCs.</p><p><strong>Methods: </strong>To assess the osteogenic differentiation of PDLSCs, the alkaline phosphatase (ALP) activity assay, Alizarin red staining, quantitative calcium analysis, and osteogenic marker detection were conducted. Transplantation PDLSCs under the dorsum of nude mice and into the rat calvarial defects were also performed. Then, FAM96B-overexpressed PDLSCs were used for RNA-sequencing and bioinformatic analysis. To evaluate the ferroptosis of PDLSCs, cytosolic reactive oxygen species (ROS), expression of glutathione peroxidase 4 (GPX4), mitochondrial morphology and functions including the mitochondrial ROS, mitochondria membrane potential, and mitochondrial respiration were detected.</p><p><strong>Results: </strong>The osteogenic indicators ALP activity, level of mineralization, and osteocalcin expression were decreased in PDLSCs by FAM96B, which demonstrated that FAM96B inhibited the osteogenic differentiation of PDLSCs. FAM96B knockdown promoted the new bone formation of PDLSCs subcutaneously transplanted to the dorsum of nude mice. Then, related biological functions were detected by the RNA-sequencing and the ferroptosis was focused. FAM96B enhanced the cytosolic ROS level and inhibited the expression of GPX4 and mitochondrial functions in PDLSCs. Hence, FAM96B promoted the ferroptosis of PDLSCs. Meanwhile, we found that FAM96B inhibition upregulated the target gene FOS like 1, AP-1 transcription factor subunit (FOSL1) expression and FOSL1 promoted the osteogenic differentiation of PDLSCs in vitro. FOSL1 also promoted the new bone formation of PDLSCs transplanted subcutaneously to the dorsum of nude mice and transplanted into rat calvarial defects. Then, the inhibitory effect of FOSL1 on the ferroptosis was confirmed.</p><p><strong>Conclusions: </strong>FAM96B depletion promoted the osteogenic differentiation and suppressed the ferroptosis of PDLSCs. FAM96B negatively regulated the downstream gene FOSL1 and FOSL1 promoted the osteogenic differentiation of PDLSCs via the ferroptosis. Hence, our findings provided a foundation for understanding the FAM96B-FOSL1 axis acting as a target for MSC mediated bone regeneration.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"15 1","pages":"471"},"PeriodicalIF":7.1,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11656916/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142855332","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}