World journal of stem cells最新文献

{"title":"Human mesenchymal stem cells exhibit altered mitochondrial dynamics and poor survival in high glucose microenvironment.","authors":"Ejlal Abu-El-Rub, Fatimah Almahasneh, Ramada R Khasawneh, Ayman Alzu'bi, Doaa Ghorab, Rawan Almazari, Huthaifa Magableh, Ahmad Sanajleh, Haitham Shlool, Mohammad Mazari, Noor S Bader, Joud Al-Momani","doi":"10.4252/wjsc.v15.i12.1093","DOIUrl":"10.4252/wjsc.v15.i12.1093","url":null,"abstract":"<p><strong>Background: </strong>Mesenchymal stem cells (MSCs) are a type of stem cells that possess relevant regenerative abilities and can be used to treat many chronic diseases. Diabetes mellitus (DM) is a frequently diagnosed chronic disease characterized by hyperglycemia which initiates many multisystem complications in the long-run. DM patients can benefit from MSCs transplantation to curb down the pathological consequences associated with hyperglycemia persistence and restore the function of damaged tissues. MSCs therapeutic outcomes are found to last for short period of time and ultimately these regenerative cells are eradicated and died in DM disease model.</p><p><strong>Aim: </strong>To investigate the impact of high glucose or hyperglycemia on the cellular and molecular characteristics of MSCs.</p><p><strong>Methods: </strong>Human adipose tissue-derived MSCs (hAD-MSCs) were seeded in low (5.6 mmol/L of glucose) and high glucose (25 mmol/L of glucose) for 7 d. Cytotoxicity, viability, mitochondrial dynamics, and apoptosis were deplored using specific kits. Western blotting was performed to measure the protein expression of phosphatidylinositol 3-kinase (PI3K), TSC1, and mammalian target of rapamycin (mTOR) in these cells.</p><p><strong>Results: </strong>hAD-MSCs cultured in high glucose for 7 d demonstrated marked decrease in their viability, as shown by a significant increase in lactate dehydrogenase (<i>P</i> < 0.01) and a significant decrease in Trypan blue (<i>P</i> < 0.05) in these cells compared to low glucose control. Mitochondrial membrane potential, indicated by tetramethylrhodamine ethyl ester (TMRE) fluorescence intensity, and nicotinamide adenine dinucleotide (NAD+)/NADH ratio were significantly dropped (<i>P</i> < 0.05 for TMRE and <i>P</i> < 0.01 for NAD+/NADH) in high glucose exposed hAD-MSCs, indicating disturbed mitochondrial function. PI3K protein expression significantly decreased in high glucose culture MSCs (<i>P</i> < 0.05 compared to low glucose) and it was coupled with significant upregulation in TSC1 (<i>P</i> < 0.05) and downregulation in mTOR protein expression (<i>P</i> < 0.05). Mitochondrial complexes I, IV, and V were downregulated profoundly in high glucose (<i>P</i> < 0.05 compared to low glucose). Apoptosis was induced as a result of mitochondrial impairment and explained the poor survival of MSCs in high glucose.</p><p><strong>Conclusion: </strong>High glucose impaired the mitochondrial dynamics and regulatory proteins in hAD-MSCs ensuing their poor survival and high apoptosis rate in hyperglycemic microenvironment.</p>","PeriodicalId":23775,"journal":{"name":"World journal of stem cells","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2023-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10762524/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139098808","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":"Stem cells and pain.","authors":"Matheus Deroco Veloso da Silva, Maiara Piva, Geovana Martelossi-Cebinelli, Mariana Stinglin Rosa Ribas, Beatriz Hoffmann Salles Bianchini, Olivia K Heintz, Rubia Casagrande, Waldiceu A Verri","doi":"10.4252/wjsc.v15.i12.1035","DOIUrl":"10.4252/wjsc.v15.i12.1035","url":null,"abstract":"<p><p>Pain can be defined as an unpleasant sensory and emotional experience caused by either actual or potential tissue damage or even resemble that unpleasant experience. For years, science has sought to find treatment alternatives, with minimal side effects, to relieve pain. However, the currently available pharmacological options on the market show significant adverse events. Therefore, the search for a safer and highly efficient analgesic treatment has become a priority. Stem cells (SCs) are non-specialized cells with a high capacity for replication, self-renewal, and a wide range of differentiation possibilities. In this review, we provide evidence that the immune and neuromodulatory properties of SCs can be a valuable tool in the search for ideal treatment strategies for different types of pain. With the advantage of multiple administration routes and dosages, therapies based on SCs for pain relief have demonstrated meaningful results with few downsides. Nonetheless, there are still more questions than answers when it comes to the mechanisms and pathways of pain targeted by SCs. Thus, this is an evolving field that merits further investigation towards the development of SC-based analgesic therapies, and this review will approach all of these aspects.</p>","PeriodicalId":23775,"journal":{"name":"World journal of stem cells","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2023-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10762525/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139098810","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":"ADSC-Exos outperform BMSC-Exos in alleviating hydrostatic pressure-induced injury to retinal ganglion cells by upregulating nerve growth factors.","authors":"Zhi-Kun Zheng, Lei Kong, Min Dai, Yi-Dan Chen, Yan-Hua Chen","doi":"10.4252/wjsc.v15.i12.1077","DOIUrl":"10.4252/wjsc.v15.i12.1077","url":null,"abstract":"<p><strong>Background: </strong>Mesenchymal stem cells (MSCs) have protective effects on the cornea, lacrimal gland, retina, and photoreceptor cell damage, which may be mediated by exosomes (exos) released by MSCs.</p><p><strong>Aim: </strong>To investigate the ameliorating effect of exos derived from different MSCs on retinal ganglion cell (RGC) injury induced by hydrostatic pressure.</p><p><strong>Methods: </strong>The RGC injury model was constructed by RGC damage under different hydrostatic pressures (40, 80, 120 mmHg). Then RGCs were cultured with adipose-derived stem cell (ADSC)-Exos and bone marrow-derived stem cell (BMSC)-Exos. Cell Counting Kit-8, transmission electron microscopy, flow cytometry, immunofluorescence, real-time quantitative polymerase chain reaction, and western blotting were performed to detect the ameliorating effect of exos on pressure-induced RGC injury.</p><p><strong>Results: </strong>ADSC-Exos and BMSC-Exos were successfully isolated and obtained. The gibbosity of RGCs was lower, the cells were irregularly ellipsoidal under pressure, and the addition of ADSC-Exos and BMSC-Exos significantly restored RGC morphology. Furthermore, the proliferative activity of RGCs was increased and the apoptosis of RGCs was inhibited. Moreover, the levels of lactate dehydrogenase and apoptosis-related proteins were increased, and the concentrations of antiapoptotic proteins and neurotrophic factors were decreased in damaged RGCs. However, the above indicators were significantly improved after ADSC-Exos and BMSC-Exos treatment.</p><p><strong>Conclusion: </strong>These findings indicated that ADSC-Exos and BMSC-Exos could ameliorate RGC injury caused by hydrostatic pressure by inhibiting apoptosis and increasing the secretion of neurotrophic factors.</p>","PeriodicalId":23775,"journal":{"name":"World journal of stem cells","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2023-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10762527/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139098807","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":"Mid-term outcomes of microfragmented adipose tissue plus arthroscopic surgery for knee osteoarthritis: A randomized, active-control, multicenter clinical trial.","authors":"Cong-Zi Wu, Zhen-Yu Shi, Zhen Wu, Wen-Jun Lin, Wei-Bo Chen, Xue-Wen Jia, Si-Cheng Xiang, Hui-Hui Xu, Qin-Wen Ge, Kai-Ao Zou, Xu Wang, Jia-Li Chen, Ping-Er Wang, Wen-Hua Yuan, Hong-Ting Jin, Pei-Jian Tong","doi":"10.4252/wjsc.v15.i12.1063","DOIUrl":"10.4252/wjsc.v15.i12.1063","url":null,"abstract":"<p><strong>Background: </strong>Osteoarthritis (OA) is the most prevalent form of degenerative whole-joint disease. Before the final option of knee replacement, arthroscopic surgery was the most widely used joint-preserving surgical treatment. Emerging regenerative therapies, such as those involving platelet-rich plasma, mesenchymal stem cells, and microfragmented adipose tissue (MFAT), have been pushed to the forefront of treatment to prevent the progression of OA. Currently, MFAT has been successfully applied to treat different types of orthopedic diseases.</p><p><strong>Aim: </strong>To assess the efficacy and safety of MFAT with arthroscopic surgery in patients with knee OA (KOA).</p><p><strong>Methods: </strong>A randomized, multicenter study was conducted between June 2017 and November 2022 in 10 hospitals in Zhejiang, China. Overall, 302 patients diagnosed with KOA (Kellgren-Lawrence grades 2-3) were randomized to the MFAT group (<i>n</i> = 151, were administered MFAT following arthroscopic surgery), or the control group (<i>n</i> = 151, were administered hyaluronic acid following arthroscopic surgery). The study outcomes were changes in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, the visual analog scale (VAS) score, the Lequesne index score, the Whole-Organ Magnetic Resonance Imaging Score (WORMS), and safety over a 24-mo period from baseline.</p><p><strong>Results: </strong>The changes in the WOMAC score (including the three subscale scores), VAS pain score, and Lequesne index score at the 24-mo mark were significantly different in the MFAT and control groups, as well as when comparing values at the posttreatment visit and those at baseline (<i>P</i> < 0.001). The MFAT group consistently demonstrated significant decreases in the WOMAC pain scores and VAS scores at all follow-ups compared to the control group (<i>P</i> < 0.05). Furthermore, the WOMAC stiffness score, WOMAC function score, and Lequesne index score differed significantly between the groups at 12 and 24 mo (<i>P</i> < 0.05). However, no significant between-group differences were observed in the WORMS at 24 mo (<i>P</i> = 0.367). No serious adverse events occurred in both groups.</p><p><strong>Conclusion: </strong>The MFAT injection combined with arthroscopic surgery treatment group showed better mid-term clinical outcomes compared to the control group, suggesting its efficacy as a therapeutic approach for patients with KOA.</p>","PeriodicalId":23775,"journal":{"name":"World journal of stem cells","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2023-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10762526/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139098809","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":"Dissecting molecular mechanisms underlying ferroptosis in human umbilical cord mesenchymal stem cells: Role of cystathionine γ-lyase/hydrogen sulfide pathway.","authors":"Bin Hu, Xiang-Xi Zhang, Tao Zhang, Wan-Cheng Yu","doi":"10.4252/wjsc.v15.i11.1017","DOIUrl":"10.4252/wjsc.v15.i11.1017","url":null,"abstract":"<p><strong>Background: </strong>Ferroptosis can induce low retention and engraftment after mesenchymal stem cell (MSC) delivery, which is considered a major challenge to the effectiveness of MSC-based pulmonary arterial hypertension (PAH) therapy. Interestingly, the cystathionine γ-lyase (CSE)/hydrogen sulfide (H₂S) pathway may contribute to mediating ferroptosis. However, the influence of the CSE/H₂S pathway on ferroptosis in human umbilical cord MSCs (HUCMSCs) remains unclear.</p><p><strong>Aim: </strong>To clarify whether the effect of HUCMSCs on vascular remodelling in PAH mice is affected by CSE/H₂S pathway-mediated ferroptosis, and to investigate the functions of the CSE/H₂S pathway in ferroptosis in HUCMSCs and the underlying mechanisms.</p><p><strong>Methods: </strong>Erastin and ferrostatin-1 (Fer-1) were used to induce and inhibit ferroptosis, respectively. HUCMSCs were transfected with a vector to overexpress or inhibit expression of CSE. A PAH mouse model was established using 4-wk-old male BALB/c nude mice under hypoxic conditions, and pulmonary pressure and vascular remodelling were measured. The survival of HUCMSCs after delivery was observed by <i>in vivo</i> bioluminescence imaging. Cell viability, iron accumulation, reactive oxygen species production, cystine uptake, and lipid peroxidation in HUCMSCs were tested. Ferroptosis-related proteins and S-sulfhydrated Kelch-like ECH-associating protein 1 (Keap1) were detected by western blot analysis.</p><p><strong>Results: </strong><i>In vivo</i>, CSE overexpression improved cell survival after erastin-treated HUCMSC delivery in mice with hypoxia-induced PAH. <i>In vitro</i>, CSE overexpression improved H₂S production and ferroptosis-related indexes, such as cell viability, iron level, reactive oxygen species production, cystine uptake, lipid peroxidation, mitochondrial membrane density, and ferroptosis-related protein expression, in erastin-treated HUCMSCs. In contrast, <i>in vivo</i>, CSE inhibition decreased cell survival after Fer-1-treated HUCMSC delivery and aggravated vascular remodelling in PAH mice. <i>In vitro</i>, CSE inhibition decreased H₂S levels and restored ferroptosis in Fer-1-treated HUCMSCs. Interestingly, upregulation of the CSE/H₂S pathway induced Keap1 S-sulfhydration, which contributed to the inhibition of ferroptosis.</p><p><strong>Conclusion: </strong>Regulation of the CSE/H₂S pathway in HUCMSCs contributes to the inhibition of ferroptosis and improves the suppressive effect on vascular remodelling in mice with hypoxia-induced PAH. Moreover, the protective effect of the CSE/H₂S pathway against ferroptosis in HUCMSCs is mediated <i>via</i> S-sulfhydrated Keap1/nuclear factor erythroid 2-related factor 2 signalling. The present study may provide a novel therapeutic avenue for improving the protective capacity of transplanted MSCs in PAH.</p>","PeriodicalId":23775,"journal":{"name":"World journal of stem cells","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2023-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10696191/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138499547","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":"Hypoxia and inflammatory factor preconditioning enhances the immunosuppressive properties of human umbilical cord mesenchymal stem cells.","authors":"Hang Li, Xiao-Qing Ji, Shu-Ming Zhang, Ri-Hui Bi","doi":"10.4252/wjsc.v15.i11.999","DOIUrl":"10.4252/wjsc.v15.i11.999","url":null,"abstract":"<p><strong>Background: </strong>Mesenchymal stem cells (MSCs) have great potential for the treatment of various immune diseases due to their unique immunomodulatory properties. However, MSCs exposed to the harsh inflammatory environment of damaged tissue after intravenous transplantation cannot exert their biological effects, and therefore, their therapeutic efficacy is reduced. In this challenging context, an <i>in vitro</i> preconditioning method is necessary for the development of MSC-based therapies with increased immunomodulatory capacity and transplantation efficacy.</p><p><strong>Aim: </strong>To determine whether hypoxia and inflammatory factor preconditioning increases the immunosuppressive properties of MSCs without affecting their biological characteristics.</p><p><strong>Methods: </strong>Umbilical cord MSCs (UC-MSCs) were pretreated with hypoxia (2% O₂) exposure and inflammatory factors (interleukin-1β, tumor necrosis factor-α, interferon-γ) for 24 h. Flow cytometry, polymerase chain reaction, enzyme-linked immunosorbent assay and other experimental methods were used to evaluate the biological characteristics of pretreated UC-MSCs and to determine whether pretreatment affected the immunosuppressive ability of UC-MSCs in coculture with immune cells.</p><p><strong>Results: </strong>Pretreatment with hypoxia and inflammatory factors caused UC-MSCs to be elongated but did not affect their viability, proliferation or size. In addition, pretreatment significantly decreased the expression of coagulation-related tissue factors but did not affect the expression of other surface markers. Similarly, mitochondrial function and integrity were retained. Although pretreatment promoted UC-MSC apoptosis and senescence, it increased the expression of genes and proteins related to immune regulation. Pretreatment increased peripheral blood mononuclear cell and natural killer (NK) cell proliferation rates and inhibited NK cell-induced toxicity to varying degrees.</p><p><strong>Conclusion: </strong>In summary, hypoxia and inflammatory factor preconditioning led to higher immunosuppressive effects of MSCs without damaging their biological characteristics.</p>","PeriodicalId":23775,"journal":{"name":"World journal of stem cells","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2023-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10696190/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138499560","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":"How to enhance the ability of mesenchymal stem cells to alleviate intervertebral disc degeneration.","authors":"Qing-Xiang Zhang, Min Cui","doi":"10.4252/wjsc.v15.i11.989","DOIUrl":"10.4252/wjsc.v15.i11.989","url":null,"abstract":"<p><p>Intervertebral disc (ID) degeneration (IDD) is one of the main causes of chronic low back pain, and degenerative lesions are usually caused by an imbalance between catabolic and anabolic processes in the ID. The environment in which the ID is located is harsh, with almost no vascular distribution within the disc, and the nutrient supply relies mainly on the diffusion of oxygen and nutrients from the blood vessels located under the endplate. The stability of its internal environment also plays an important role in preventing IDD. The main feature of disc degeneration is a decrease in the number of cells. Mesenchymal stem cells have been used in the treatment of disc lesions due to their ability to differentiate into nucleus pulposus cells in a nonspecific anti-inflammatory manner. The main purpose is to promote their regeneration. The current aim of stem cell therapy is to replace the aged and metamorphosed cells in the ID and to increase the content of the extracellular matrix. The treatment of disc degeneration with stem cells has achieved good efficacy, and the current challenge is how to improve this efficacy. Here, we reviewed current treatments for disc degeneration and summarize studies on stem cell vesicles, enhancement of therapeutic effects when stem cells are mixed with related substances, and improvements in the efficacy of stem cell therapy by adjuvants under adverse conditions. We reviewed the new approaches and ideas for stem cell treatment of disc degeneration in order to contribute to the development of new therapeutic approaches to meet current challenges.</p>","PeriodicalId":23775,"journal":{"name":"World journal of stem cells","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2023-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10696189/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138499548","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":"Potential of dental pulp stem cells and their products in promoting peripheral nerve regeneration and their future applications.","authors":"Wen-Bo Xing, Shu-Ting Wu, Xin-Xin Wang, Fen-Yao Li, Ruo-Xuan Wang, Ji-Hui He, Jiao Fu, Yan He","doi":"10.4252/wjsc.v15.i10.960","DOIUrl":"https://doi.org/10.4252/wjsc.v15.i10.960","url":null,"abstract":"<p><p>Peripheral nerve injury (PNI) seriously affects people's quality of life. Stem cell therapy is considered a promising new option for the clinical treatment of PNI. Dental stem cells, particularly dental pulp stem cells (DPSCs), are adult pluripotent stem cells derived from the neuroectoderm. DPSCs have significant potential in the field of neural tissue engineering due to their numerous advantages, such as easy isolation, multidifferentiation potential, low immunogenicity, and low transplant rejection rate. DPSCs are extensively used in tissue engineering and regenerative medicine, including for the treatment of sciatic nerve injury, facial nerve injury, spinal cord injury, and other neurodegenerative diseases. This article reviews research related to DPSCs and their advantages in treating PNI, aiming to summarize the therapeutic potential of DPSCs for PNI and the underlying mechanisms and providing valuable guidance and a foundation for future research.</p>","PeriodicalId":23775,"journal":{"name":"World journal of stem cells","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2023-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10631371/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134649969","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":"MicroRNA-584-5p/RUNX family transcription factor 2 axis mediates hypoxia-induced osteogenic differentiation of periosteal stem cells.","authors":"Jia-Jia Lu, Xiao-Jian Shi, Qiang Fu, Yong-Chuan Li, Lei Zhu, Nan Lu","doi":"10.4252/wjsc.v15.i10.979","DOIUrl":"10.4252/wjsc.v15.i10.979","url":null,"abstract":"<p><strong>Background: </strong>The hypoxic environment during bone healing is important in regulating the differentiation of periosteal stem cells (PSCs) into osteoblasts or chondrocytes; however, the underlying mechanisms remain unclear.</p><p><strong>Aim: </strong>To determine the effect of hypoxia on PSCs, and the expression of microRNA-584-5p (miR-584-5p) and RUNX family transcription factor 2 (RUNX2) in PSCs was modulated to explore the impact of the miR-584-5p/RUNX2 axis on hypoxia-induced osteogenic differentiation of PSCs.</p><p><strong>Methods: </strong>In this study, we isolated primary mouse PSCs and stimulated them with hypoxia, and the characteristics and functional genes related to PSC osteogenic differentiation were assessed. Constructs expressing miR-584-5p and RUNX2 were established to determine PSC osteogenic differentiation.</p><p><strong>Results: </strong>Hypoxic stimulation induced PSC osteogenic differentiation and significantly increased calcified nodules, intracellular calcium ion levels, and alkaline phosphatase (ALP) activity in PSCs. Osteogenic differentiation-related factors such as RUNX2, bone morphogenetic protein 2, hypoxia-inducible factor 1-alpha, and ALP were upregulated; in contrast, miR-584-5p was downregulated in these cells. Furthermore, upregulation of miR-584-5p significantly inhibited RUNX2 expression and hypoxia-induced PSC osteogenic differentiation. RUNX2 was the target gene of miR-584-5p<i>,</i> antagonizing miR-584-5p inhibition in hypoxia-induced PSC osteogenic differentiation.</p><p><strong>Conclusion: </strong>Our study showed that the interaction of miR-584-5p and RUNX2 could mediate PSC osteogenic differentiation induced by hypoxia.</p>","PeriodicalId":23775,"journal":{"name":"World journal of stem cells","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2023-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10631372/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134649968","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":"Interferon-γ priming enhances the therapeutic effects of menstrual blood-derived stromal cells in a mouse liver ischemia-reperfusion model.","authors":"Qi Zhang,&nbsp;Si-Ning Zhou,&nbsp;Jia-Min Fu,&nbsp;Li-Jun Chen,&nbsp;Yang-Xin Fang,&nbsp;Zhen-Yu Xu,&nbsp;Hui-Kang Xu,&nbsp;Yin Yuan,&nbsp;Yu-Qi Huang,&nbsp;Ning Zhang,&nbsp;Yi-Fei Li,&nbsp;Charlie Xiang","doi":"10.4252/wjsc.v15.i9.876","DOIUrl":"https://doi.org/10.4252/wjsc.v15.i9.876","url":null,"abstract":"<p><strong>Background: </strong>Mesenchymal stem cells (MSCs) have been used in liver transplantation and have certain effects in alleviating liver ischemia-reperfusion injury (IRI) and regulating immune rejection. However, some studies have indicated that the effects of MSCs are not very significant. Therefore, approaches that enable MSCs to exert significant and stable therapeutic effects are worth further study.</p><p><strong>Aim: </strong>To enhance the therapeutic potential of human menstrual blood-derived stromal cells (MenSCs) in the mouse liver ischemia-reperfusion (I/R) model <i>via</i> interferon-γ (IFN-γ) priming.</p><p><strong>Methods: </strong>Apoptosis was analyzed by flow cytometry to evaluate the safety of IFN-γ priming, and indoleamine 2,3-dioxygenase (IDO) levels were measured by quantitative real-time reverse transcription polymerase chain reaction, western blotting, and ELISA to evaluate the efficacy of IFN-γ priming. <i>In vivo</i>, the liver I/R model was established in male C57/BL mice, hematoxylin and eosin and TUNEL staining was performed and serum liver enzyme levels were measured to assess the degree of liver injury, and regulatory T cell (Treg) numbers in spleens were determined by flow cytometry to assess immune tolerance potential. Metabolomics analysis was conducted to elucidate the potential mechanism underlying the regulatory effects of primed MenSCs. <i>In vitro</i>, we established a hypoxia/reoxygenation (H/R) model and analyzed apoptosis by flow cytometry to investigate the mechanism through which primed MenSCs inhibit apoptosis. Transmission electron microscopy, western blotting, and immunofluorescence were used to analyze autophagy levels.</p><p><strong>Results: </strong>IFN-γ-primed MenSCs secreted higher levels of IDO, attenuated liver injury, and increased Treg numbers in the mouse spleens to greater degrees than untreated MenSCs. Metabolomics and autophagy analyses proved that primed MenSCs more strongly induced autophagy in the mouse livers. In the H/R model, autophagy inhibitors increased the level of H/R-induced apoptosis, indicating that autophagy exerted protective effects. In addition, primed MenSCs decreased the level of H/R-induced apoptosis <i>via</i> IDO and autophagy. Further rescue experiments proved that IDO enhanced the protective autophagy by inhibiting the mammalian target of rapamycin (mTOR) pathway and activating the AMPK pathway.</p><p><strong>Conclusion: </strong>IFN-γ-primed MenSCs exerted better therapeutic effects in the liver I/R model by secreting higher IDO levels. MenSCs and IDO activated the AMPK-mTOR-autophagy axis to reduce IRI, and IDO increased Treg numbers in the spleen and enhanced the MenSC-mediated induction of immune tolerance. Our study suggests that IFN-γ-primed MenSCs may be a novel and superior MSC product for liver transplantation in the future.</p>","PeriodicalId":23775,"journal":{"name":"World journal of stem cells","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2023-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10600742/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71414086","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}