{"title":"Therapeutic potential of placenta-derived stem cells cultivated on noggin-loaded nanochitosan/polypyrrole-alginate conductive scaffold to restore spinal cord injury.","authors":"Asma Manzari-Tavakoli, Amirhesam Babajani, Nasim Vousooghi, Ali Moghimi, Roghayeh Tarasi, Fahimeh Safaeinejad, Samira Norouzi, Soheyl Bahrami, Hassan Niknejad","doi":"10.1186/s13287-024-04104-5","DOIUrl":"10.1186/s13287-024-04104-5","url":null,"abstract":"<p><strong>Objective: </strong>Spinal cord injury (SCI) is a severe and permanent nerve damage condition that poses significant burdens on individuals and society. Various therapeutic approaches have been explored to mitigate the consequences of SCI. Tissue engineering and regenerative medicine have emerged as a promising avenue for addressing this issue. This study aims to investigate the potential of a nanochitosan/polypyrrole-alginate conductive scaffold, loaded with the Noggin growth factor, an inhibitor of BMP-4 signaling, and human amniotic epithelial cells (hAECs), in promoting the regeneration of SCI in animal models.</p><p><strong>Methods: </strong>The attachment and distribution of isolated hAECs on a fabricated nanochitosan/polypyrrole-alginate conductive scaffold were assessed using SEM. Additionally, the neural differentiation of hAECs on the scaffold was investigated by analyzing the expression of specific neuronal (Calca, Fox3), oligodendrocyte (MBP), and astrocyte (GFAP) genes in vitro. To evaluate the combined effect of the scaffold and Noggin growth factor in animal models, a Noggin-loaded scaffold was designed using bioinformatics, and the loading and release capacity of Noggin were measured. For in vivo studies, rats underwent laminectomy and were transplanted with the scaffold, either alone or with Noggin and DII labeled- hAECs, at the T10-T11 level. Motor functions of the animal were evaluated using BBB scoring weekly in an open field for four weeks. Furthermore, the expression of neural genes and immunohistochemical tests were evaluated after four weeks.</p><p><strong>Results: </strong>hAECs exhibited uniform distribution and attachment to the scaffold. In vitro differentiation analyses showed increased expression of Calca, Fox3, MBP, and GFAP genes. Docking results indicated that Noggin could interact with chitosan nanoparticles through hydrogen bonds. The chitosan nanoparticles effectively loaded 22.6% of exposed Noggin, and the scaffold released 28.5% of the total incorporated Noggin. In vivo studies demonstrated that transplanting nanochitosan/polypyrrole-alginate conductive scaffolds with DII labeled-hAECs, with or without Noggin, improved motor functions in animal models. The assessment of gene expression patterns in transplanted hAECs revealed that neuronal (Calca, Fox3) and oligodendrocyte (MBP) genes in the injured spinal cord of the animal models were upregulated. Histopathological analysis showed a reduction in inflammation and glial scar formation, while neural fiber regeneration increased in the treated animals. Also, DII labeled-hAECs in the lesion site were alive after a period of four weeks.</p><p><strong>Conclusion: </strong>Based on these findings, it can be inferred that the integrative therapeutic effects of human amniotic epithelial cells, nanochitosan/polypyrrole-Alginate conductive scaffold, and Noggin (as BMP-4 signaling inhibitor) represents a promising and innovative approach in the field of transl","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"15 1","pages":"497"},"PeriodicalIF":7.1,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11668012/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882989","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":"Preclinical study of novel human allogeneic adipose tissue-derived mesenchymal stem cell sheets toward a first-in-human clinical trial for myopic chorioretinal atrophy.","authors":"Norimichi Nagano, Yoshio Hirano, Masayo Kimura, Hiroshi Morita, Tsutomu Yasukawa","doi":"10.1186/s13287-024-04118-z","DOIUrl":"10.1186/s13287-024-04118-z","url":null,"abstract":"<p><strong>Background: </strong>Mesenchymal stem cells may have neuroprotective and tissue regenerative capabilities and the potential to rescue retinal degeneration in chorioretinal diseases including myopic chorioretinal atrophy. Transplantation of human (allogeneic) adipose tissue-derived mesenchymal stem cell (adMSC) suspensions has been clinically conducted to treat retinal degenerative diseases. However, serious side effects including proliferative vitreoretinopathy and epiretinal membrane formation have been reported. PharmaBio Corporation fabricated novel adMSC sheets with a Bruch's membrane-like structure using our original method, potentially overcoming these problems. We evaluated the characteristics of newly developed adMSC sheets named PAL-222 and assessed their safety and efficacy in rats with congenital retinal degeneration (RCS rats) to obtain the proof-of-concept for the first-in-human clinical trial for myopic chorioretinal atrophy.</p><p><strong>Methods: </strong>We measured the viability of cells obtained from PAL-222, examined cell surface antigens by flow cytometry, measured the vascular endothelial growth factor (VEGF) and pigment epithelium-derived factor (PEDF) secretory ability, examined the expression of types I and IV collagen and elastin by immunostaining. We performed a transwell in vitro migration assay to evaluate durability and similarity to retinal pigment epithelium (RPE) and checked in vitro tumorigenicity. In an in vivo experiment, we transplanted PAL-222 into the subretinal space of RCS rats and evaluated the safety and efficacy.</p><p><strong>Results: </strong>Viability of cells obtained from PAL-222 was 88.1%. The rate of positive markers such as CD90, CD73, CD105 and CD44 exceeded 90%; that of the negative markers such as CD34, CD11b, CD19, CD45 and HLA-DR was less than 2%. PAL-222 secreted significant amounts of VEGF and PEDF and expressed types I and IV collagen and elastin. The migration assay showed that PAL-222 preserved the sheet structure without cell migration. No chromosomal aberration or colony formation was observed in in vitro tumorigenicity tests. PAL-222 transplantation suppressed the progression of retinal degeneration by preserving the outer nuclear layer without negative changes in RCS rats, suggesting a retinoprotective effect.</p><p><strong>Conclusions: </strong>We confirmed the efficacy and safety of PAL-222 and are currently conducting a clinical trial to treat myopic chorioretinal atrophy. Transplantation of these novel adMSC sheets may be a promising therapy for myopic chorioretinal atrophy.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov, Identifier: NCT05658237. URL: https://classic.</p><p><strong>Clinicaltrials: </strong>gov/ct2/show/NCT05658237 .</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"15 1","pages":"498"},"PeriodicalIF":7.1,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11667907/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882988","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}
Huaqing Yang, Xinyu Li, Liping Que, Han Chen, Liping Zhan, Dunhua Zhou, Yang Li, Shaofen Lin, Yin Wang, Xiaojun Wu, Xiawei Han, Zhengzhou Wu, Danping Zhong, Ke Huang, Honggui Xu, Jianpei Fang
{"title":"A novel conditioning regimen with pre-transplantation immunosuppression reduces the complication rates in hematopoietic stem cell transplantation in transfusion-dependent β-thalassemia.","authors":"Huaqing Yang, Xinyu Li, Liping Que, Han Chen, Liping Zhan, Dunhua Zhou, Yang Li, Shaofen Lin, Yin Wang, Xiaojun Wu, Xiawei Han, Zhengzhou Wu, Danping Zhong, Ke Huang, Honggui Xu, Jianpei Fang","doi":"10.1186/s13287-024-04103-6","DOIUrl":"10.1186/s13287-024-04103-6","url":null,"abstract":"<p><strong>Background: </strong>Allo-HSCT is a curative therapy for patients with transfusion-dependent thalassemia (TDT). The high incidence of transplant-related complications is becoming an obstacle to safe and effective unrelated donor (URD) transplantation.</p><p><strong>Methods: </strong>In this retrospective study, we reported the survival outcomes and complications of transplantation in thalassemia patients using a novel regimen consisting of pre-transplantation immunosuppression (PTIS) and modified myeloablative conditioning based on intravenous busulfan, cyclophosphamide, fludarabine, and rabbit anti-human thymocyte immunoglobulin.</p><p><strong>Results: </strong>A total of 88 thalassemia patients received the novel conditioning regimen (NCR group), while 118 patients received the conventional conditioning regimen (CCR group). The median age at HSCT in the NCR group was older (7 years vs. 4 years, p < 0.05). No patient in the NCR group experienced primary graft failure, while the 3-year probabilities of OS and TFS were 96.6% and 93.2%, respectively. Even when the intensity of conditioning was reduced, OS (94.8% vs. 94.3%, p = 0.848) and TFS (89.8% vs. 92.5%, p = 0.663) in URD transplants in the NCR group were comparable to those in the CCR group, while the risk of autoimmune hemolytic anemia (AIHA) (0% vs. 15.1%) was lower. In addition, the NCR group had lower rates of mixed chimerism (7.1%).</p><p><strong>Conclusions: </strong>URD transplantation can achieve a comparable prognosis to matched sibling donor (MSD) transplantation with a lower incidence of AIHA due to PTIS and modified myeloablative conditioning regimen.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"15 1","pages":"495"},"PeriodicalIF":7.1,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11663346/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872370","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":"Exosomes derived from hypoxic mesenchymal stem cells restore ovarian function by enhancing angiogenesis.","authors":"Qingxi Qu, Linghong Liu, Limei Wang, Yuqian Cui, Chunxiao Liu, Xuanxuan Jing, Xiaoxuan Xu","doi":"10.1186/s13287-024-04111-6","DOIUrl":"10.1186/s13287-024-04111-6","url":null,"abstract":"<p><strong>Background: </strong>hucMSC-exosomes can be engineered to strengthen their therapeutic potential, and the present study aimed to explore whether hypoxic preconditioning can enhance the angiogenic potential of hucMSC-exosomes in an experimental model of POF.</p><p><strong>Methods: </strong>Primary hucMSCs and ROMECs were isolated from fresh tissue samples and assessed through a series of experiments. Exosomes were isolated from hucMSCs under normoxic or hypoxic conditions (norm-Exos and hypo-Exos, respectively) and then characterized using classic experimental methods. Based on a series of angiogenesis-related assays, we found that hypo-Exos significantly promoted ROMEC proliferation, migration, and tube formation and increased angiogenesis-promoting molecules in vitro. Histology, immunohistochemistry, and immunofluorescence experiments in a rat model of POF demonstrated that hypoxia pretreatment strengthens the therapeutic angiogenic effect of hucMSC-exosomes in vivo. Subsequently, high-throughput miRNA sequencing, qRT‑PCR analysis, and western blotting were employed to identify the potential molecular mechanism.</p><p><strong>Results: </strong>We found that hypo-Exos enhance endothelial function and angiogenesis via the transfer of miR-205-5p in vitro and in vivo. Finally, based on the results of bioinformatics analysis, dual luciferase reporter assays, and gain- and loss-of-function studies, we found evidence indicating that exosomal miR-205-5p enhances angiogenesis by targeting the PTEN/PI3K/AKT/mTOR signalling pathway. These results indicated for the first time that exosomes derived from hypoxia-conditioned hucMSCs strongly enhance angiogenesis via the transfer of miR-205-5p by targeting the PTEN/PI3K/AKT/mTOR signalling pathway.</p><p><strong>Conclusions: </strong>Our findings provide a theoretical basis and demonstrate the potential application of a novel cell-free approach with stem cell-derived products in the treatment of POF.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"15 1","pages":"496"},"PeriodicalIF":7.1,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11663355/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872621","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":"Effect of traction therapy on muscle satellite cell proliferation and differentiation in a rat model of knee stiffness.","authors":"Xiaoqian Lv, Xiaoyu Wang, Jianxing Yue, Xin Wang, Haoyue Chen, Qiang Gao","doi":"10.1186/s13287-024-04108-1","DOIUrl":"10.1186/s13287-024-04108-1","url":null,"abstract":"<p><strong>Background: </strong>In the rat knee stiffness model, the duration of traction treatment is mostly 20-40 min; however, relatively few studies have been conducted on longer traction treatment of extended knee stiffness in rats. Therefore, the aim of this study was to explore the efficacy of prolonged traction and its mechanism of action in extended knee stiffness in rats.</p><p><strong>Methods: </strong>The model of extended knee joint stiffness was established in rats and treated with powered flexion position traction. On the 10th and 20th days respectively, passive range of motion (PROM) assessments and musculoskeletal ultrasound were conducted. Rectus femoris muscle tissues were taken for Western blotting (WB) to detect the expression of muscle satellite cells proliferation and differentiation signaling factors. Histopathological staining was used to evaluate the degree of muscle atrophy and muscle fibrosis in the rectus femoris muscle, and immunofluorescence double staining was used to detect proliferation of muscle satellite cells number. The results from these analyses were used to assess the therapeutic outcomes of the traction treatment.</p><p><strong>Results: </strong>The findings indicated that chronic persistent traction significantly improved joint mobility, notably enhanced the proliferation of muscle satellite cells, and inhibited their differentiation. Furthermore, the treatment facilitated the repair and regeneration of damaged tissues, reduced muscular atrophy and fibrosis in the rectus femoris muscle, and alleviated knee stiffness.</p><p><strong>Conclusion: </strong>Chronic persistent traction can effectively relieve knee joint stiffness, and its mechanism is related to the activation and proliferation of the rectus femoris muscle satellite cells, thereby promoting the repair and regeneration of damaged skeletal muscle.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"15 1","pages":"490"},"PeriodicalIF":7.1,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11662639/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872603","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":"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":"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":"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}
Xing Qi, Zhiliang Xu, Xingchen Liu, Yanan Ren, Yecheng Jin, Wenjie Sun, Jiangxia Li, Duo Liu, Shuwei Liu, Qiji Liu, Xi Li
{"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}