Stem Cells International最新文献

{"title":"Rapid, Efficient, and Universally Applicable Genetic Engineering of Intestinal Organoid with a Sequential Monolayer to Three-Dimensional Strategy","authors":"Weili Han, Guofang Lu, Sheng Zhao, Rui Wang, Haohao Zhang, Kun Liu, Yongzhan Nie, Jiaqiang Dong","doi":"10.1155/2024/2005845","DOIUrl":"https://doi.org/10.1155/2024/2005845","url":null,"abstract":"Genetically modified intestinal organoids are being explored as potential surrogates of immortalized cell lines and gene-engineered animals. However, genetic manipulation of intestinal organoids is time-consuming, and the efficiency is far beyond satisfactory. To ensure the yield of the genetically modified organoids, large quantity of starting materials is required, and the procedure usually takes more than 10 days. Two major obstacles that restrict the genetic delivery efficiency are the three-dimensional culture condition and that the genetic delivery is carried out in cell suspensions. In the present study, we introduce a novel highly efficient strategy for building genetically modified intestinal organoids in which genetic delivery was performed in freshly established monolayer primary intestinal epithelial cells under two-dimensional conditions and subsequentially transformed into three-dimensional organoids. The total procedure can be finished within 10 hr while displaying much higher efficiency than the traditional methods. Furthermore, this strategy allowed for the selection of transgenic cells in monolayer conditions before establishing high-purity genetically modified intestinal organoids.","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"31 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141153309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exosomal miR-423-5p Derived from Cerebrospinal Fluid Pulsation Stress-Stimulated Osteoblasts Improves Angiogenesis of Endothelial Cells via DUSP8/ERK1/2 Signaling Pathway","authors":"Hailong Li, Yiqun He, Xujun Chen, Aolei Yang, Feizhou Lyu, Youhai Dong","doi":"10.1155/2024/5512423","DOIUrl":"https://doi.org/10.1155/2024/5512423","url":null,"abstract":"Exosomes secreted from osteoblasts (OBs) can regulate the angiogenesis of endothelial cells (ECs); however, whether cerebrospinal fluid pulsation (CSFP) stress, a special mechanical stimulation, can influence the cell’s communication in the context of angiogenesis remains unknown. In this study, the effect of exosomes derived from CSFP stress-stimulated OBs on facilitating the angiogenesis of ECs was investigated. First, OBs were cultured in a CSFP bioreactor, and exosomes derived from OBs were isolated and identified. Cell Counting Kit 8 assay, transwell migration assay, wound healing migration assay, and tube formation assay were conducted to assess the effects of CSFP stress-stimulated OBs-derived exosomes (CSFP-Exos) on the angiogenesis of ECs. Then high-throughput RNA sequencing was used to determine the miRNA profiles of Non-CSFP stress-stimulated OBs-derived exosomes (NCSFP-Exos) and CSFP-Exos, and the luciferase reporter gene assay was performed to confirm the binging of miR-423-5p to DUSP8. In addition, the Matrigel plug assay was performed to explore whether exosomal miR-423-5p has the same effects <i>in vivo</i>. Our results suggested that CSFP-Exos can promote the angiogenesis of ECs, and miR-423-5p was enriched in CSFP-Exos. Moreover, miR-423-5p could promote the effect of angiogenesis via directly targeting dual-specificity phosphatase 8 (DUSP8), which inhibited the ERK1/2 signaling pathway. In conclusion, exosomal miR-423-5p derived from CSFP stress-stimulated OBs could promote the angiogenesis of ECs by the DUSP8/ERK1/2 signaling pathway.","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2015 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140930388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Improving Cutaneous Wound Healing in Diabetic Mice Using Naturally Derived Tissue-Engineered Biological Dressings Produced under Serum-Free Conditions","authors":"Meryem Safoine, Caroline Paquette, Gabrielle-Maude Gingras, Julie Fradette","doi":"10.1155/2024/3601101","DOIUrl":"https://doi.org/10.1155/2024/3601101","url":null,"abstract":"Long-term diabetes often leads to chronic wounds refractory to treatment. Cell-based therapies are actively investigated to enhance cutaneous healing. Various cell types are available to produce biological dressings, such as adipose-derived stem/stromal cells (ASCs), an attractive cell source considering their abundancy, accessibility, and therapeutic secretome. In this study, we produced human ASC-based dressings under a serum-free culture system using the self-assembly approach of tissue engineering. The dressings were applied every 4 days to full-thickness 8-mm splinted skin wounds created on the back of polygenic diabetic NONcNZO10/LtJ mice and streptozotocin-induced diabetic K14-H2B-GFP mice. Global wound closure kinetics evaluated macroscopically showed accelerated wound closure in both murine models, especially for NONcNZO10/LtJ; the treated group reaching 98.7% ± 2.3% global closure compared to 76.4% ± 11.8% for the untreated group on day 20 (<span><svg height=\"11.7782pt\" style=\"vertical-align:-3.42938pt\" version=\"1.1\" viewbox=\"-0.0498162 -8.34882 18.973 11.7782\" width=\"18.973pt\" xmlns=\"http://www.w3.org/2000/svg\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"><g transform=\"matrix(.013,0,0,-0.013,0,0)\"></path></g><g transform=\"matrix(.013,0,0,-0.013,11.342,0)\"></path></g></svg><span></span><span><svg height=\"11.7782pt\" style=\"vertical-align:-3.42938pt\" version=\"1.1\" viewbox=\"22.555183800000002 -8.34882 34.448 11.7782\" width=\"34.448pt\" xmlns=\"http://www.w3.org/2000/svg\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"><g transform=\"matrix(.013,0,0,-0.013,22.605,0)\"></path></g><g transform=\"matrix(.013,0,0,-0.013,28.845,0)\"></path></g><g transform=\"matrix(.013,0,0,-0.013,31.809,0)\"><use xlink:href=\"#g113-49\"></use></g><g transform=\"matrix(.013,0,0,-0.013,38.049,0)\"><use xlink:href=\"#g113-49\"></use></g><g transform=\"matrix(.013,0,0,-0.013,44.289,0)\"><use xlink:href=\"#g113-49\"></use></g><g transform=\"matrix(.013,0,0,-0.013,50.529,0)\"></path></g></svg>).</span></span> Histological analyses revealed that treated wounds exhibited healed skin of better quality with a well-differentiated epidermis and a more organized, homogeneous, and 1.6-fold thicker granulation tissue. Neovascularization, assessed by CD31 labeling, was 2.5-fold higher for the NONcNZO10/LtJ treated wounds. We thus describe the beneficial impact on wound healing of biologically active ASC-based dressings produced under an entirely serum-free production system facilitating clinical translation.","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"85 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140828197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mesenchymal Stem Cells and Extracellular Vesicles: Therapeutic Potential in Organ Transplantation","authors":"Wennuo Pan, Shaohan Li, Kunsheng Li, Pengyu Zhou","doi":"10.1155/2024/2043550","DOIUrl":"https://doi.org/10.1155/2024/2043550","url":null,"abstract":"At present, organ transplantation remains the most appropriate therapy for patients with end-stage organ failure. However, the field of organ transplantation is still facing many challenges, including the shortage of organ donors, graft function damage caused by organ metastasis, and antibody-mediated immune rejection. It is therefore urgently necessary to find new and effective treatment. Stem cell therapy has been regarded as a “regenerative medicine technology.” Mesenchymal stem cells (MSCs), as the most common source of cells for stem cell therapy, play an important role in regulating innate and adaptive immune responses and have been widely used in clinical trials for the treatment of autoimmune and inflammatory diseases. Increasing evidence has shown that MSCs mainly rely on paracrine pathways to exert immunomodulatory functions. In addition, mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) are the main components of paracrine substances of MSCs. Herein, an overview of the application of the function of MSCs and MSC-EVs in organ transplantation will focus on the progress reported in recent experimental and clinical findings and explore their uses for graft preconditioning and recipient immune tolerance regulation. Additionally, the limitations on the use of MSC and MSC-EVs are also discussed, covering the isolation of exosomes and preservation techniques. Finally, the opportunities and challenges for translating MSCs and MSC-EVs into clinical practice of organ transplantation are also evaluated.","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"12 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140800934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human Placental Mesenchymal Stem Cells-Exosomes Alleviate Endothelial Barrier Dysfunction via Cytoskeletal Remodeling through hsa-miR-148a-3p/ROCK1 Pathway","authors":"Yuzhen Lv, Wenqin Yu, Ruiui Xuan, Yulu Yang, Xiaolan Xue, Xiaowei Ma","doi":"10.1155/2024/2172632","DOIUrl":"https://doi.org/10.1155/2024/2172632","url":null,"abstract":"<i>Background</i>. Endothelial barrier disruption of human pulmonary vascular endothelial cells (HPVECs) is an important pathogenic factor for acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Mesenchymal stem cells-exosome (MSCs-Exo) represents an ideal carrier for cell-free therapy. The therapeutic implication and underlying mechanism of human placental MSCs-Exo (HPMSCs-Exo) in ALI/ARDS need to be further explored. <i>Materials and Methods</i>. HPMSCs-Exo was extracted from HPMSCs and characterized. Then, the therapeutic effects of exosomes were evaluated in ALI mice and HPVECs. RNA-sequencing was applied to reveal the miRNA profile of HPMSCs-Exo and differentially expressed genes (DEGs) in HPMSCs-Exo-pretreated HPVECs. The targets of miRNAs were predicted by bioinformatics methods and correlated to DEGs. Finally, the role of hsa-miR-148a-3p/ROCK1 pathway in HPVECs has been further discussed. <i>Results</i>. The results showed that HPMSCs-Exo could downregulate Rho-associated coiled-coil-containing protein kinase 1 (ROCK1), upregulate the expression of zonula occludens-1 (ZO-1) and F-actin, promote HPVECs migration and tube formation, reduce cytoskeletal disorders and cell permeability, and thus improve ALI/ARDS. RNA-sequencing revealed the DEGs were mainly enriched in cell junction, angiogenesis, inflammation, and energy metabolism. HPMSCs-Exo contains multiple miRNAs which are associated with cytoskeletal function; the expression abundance of hsa-miR-148a-3p is the highest. Bioinformatic analysis identified ROCK1 as a target of hsa-miR-148a-3p. The overexpression of hsa-miR-148a-3p in HPMSCs-Exo promoted the migration and tube formation of HPVECs and reduced ROCK1 expression. However, the overexpression of ROCK1 on HPVECs reduced the therapeutic effect of HPMSCs-Exo. <i>Conclusions</i>. HPMSCs-Exo represents a protective regimen against endothelial barrier disruption of HPVECs in ALI/ARDS, and the hsa-miR-148a-3p/ROCK1 pathway plays an important role in this therapeutics implication.","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"218 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140627995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aucubin Promotes Osteogenic Differentiation and Facilitates Bone Formation through the lncRNA-H19 Driven Wnt/β-Catenin Signaling Regulatory Axis","authors":"Yong-xin Mai, Zhi-peng Li, Feng-xiang Pang, Shu-ting Zhou, Nan Li, Yu-yan Wang, Jin-fang Zhang","doi":"10.1155/2024/5388064","DOIUrl":"https://doi.org/10.1155/2024/5388064","url":null,"abstract":"<i>Objectives</i>. Traditional Chinese medicine <i>Cortex Eucommiae</i> has been used to treat bone fracture for hundreds of years, which exerts a significant improvement in fracture healing. Aucubin, a derivative isolated from <i>Cortex Eucommiae</i>, has been demonstrated to possess anti-inflammatory, immunoregulatory, and antioxidative potential. In the present study, our aim was to explore its function in bone regeneration and elucidate the underlying mechanism. <i>Materials and Methods</i>. The effects of Aucubin on osteoblast and osteoclast were examined in mouse bone marrow-derived mesenchymal stem cells (BM-MSCs) and RAW 264.7 cells, respectively. Moreover, the lncRNA H19 and Wnt/<i>β</i>-catenin signaling were detected by qPCR examination, western blotting, and luciferase activity assays. Using the femur fracture mice model, the <i>in vivo</i> effect of Aucubin on bone formation was monitored by X-ray, micro-CT, histomorphometry, and immunohistochemistry staining. <i>Results</i>. In the present study, Aucubin was found to significantly promote osteogenic differentiation <i>in vitro</i> and stimulated bone formation <i>in vivo</i>. Regarding to the underlying mechanism, H19 was found to be obviously upregulated by Aucubin in MSCs and thus induced the activation of Wnt/<i>β</i>-catenin signaling. Moreover, H19 knockdown partially reversed the Aucubin-induced osteogenic differentiation and successfully suppressed the activation of Wnt/<i>β</i>-catenin signaling. We therefore suggested that Aucubin induced the activation of Wnt/<i>β</i>-catenin signaling through promoting H19 expression. <i>Conclusion</i>. Our results demonstrated that Aucubin promoted osteogenesis <i>in vitro</i> and facilitated fracture healing <i>in vivo</i> through the H19-Wnt/<i>β</i>-catenin regulatory axis.","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"18 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140576724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HMGB1 Modulates High Glucose-Induced Erroneous Differentiation of Tendon Stem/Progenitor Cells through RAGE/β-Catenin Pathway","authors":"Panpan Lu, Guangchun Dai, Liu Shi, Yingjuan Li, Ming Zhang, Hao Wang, Yunfeng Rui","doi":"10.1155/2024/2335270","DOIUrl":"https://doi.org/10.1155/2024/2335270","url":null,"abstract":"The association of tendinopathy with diabetes has been well recognized. Tendon stem/progenitor cells (TSPCs) play critical roles in tendon repair, regeneration, and homeostasis maintenance. Diabetic TSPCs exhibit enhanced erroneous differentiation and are involved in the pathogenesis of diabetic tendinopathy, whereas the underlying mechanism of the erroneous differentiation of TSPCs remains unclear. Here, we showed that high glucose treatment promoted the erroneous differentiation of TSPCs with increased osteogenic differentiation capacity and decreased tenogenic differentiation ability, and stimulated the expression and further secretion of HMGB1 in TSPCs and. Functionally, exogenous HMGB1 significantly enhanced the erroneous differentiation of TSPCs, while HMGB1 knockdown mitigated high glucose-promoted erroneous differentiation of TSPCs. Mechanistically, the RAGE/<i>β</i>-catenin signaling was activated in TSPCs under high glucose, and HMGB1 knockdown inhibited the activity of RAGE/<i>β</i>-catenin signaling. Inhibition of RAGE/<i>β</i>-catenin signaling could ameliorate high glucose-induced erroneous differentiation of TSPCs. These results indicated that HMGB1 regulated high glucose-induced erroneous differentiation of TSPCs through the RAGE/<i>β</i>-catenin signaling pathway. Collectively, our findings suggest a novel essential mechanism of the erroneous differentiation of TSPCs, which might contribute to the pathogenesis of diabetic tendinopathy and provide a promising therapeutic target and approach for diabetic tendinopathy.","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"37 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140576408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TLR3 Agonist Amplifies the Anti-Inflammatory Potency of ADSCs via IL-10-Mediated Macrophage Polarization in Acute Pancreatitis","authors":"Jianxing Liu, Wenjing Yan, Shanshan Chen, Yingjie Sun, Fangfang Zhang, Yue Yang, Liang Jin","doi":"10.1155/2024/5579228","DOIUrl":"https://doi.org/10.1155/2024/5579228","url":null,"abstract":"The immunoregulatory role of mesenchymal stem cells (MSCs) in inflammation is heterogeneous and can exhibit anti-inflammatory or proinflammatory properties depending on the microenvironment. We herein observed that the activation of Toll-like receptor 3 (TLR3) by polyinosinic : polycytidylic acid (poly(I : C)) stimulation facilitated the transformation of adipose-derived stem cells (ADSCs) into an anti-inflammatory phenotype. The enhanced anti-inflammatory properties were assessed in a taurocholate-induced pancreatitis model. The results demonstrated that poly(I : C) pretreated ADSCs exhibited enhanced anti-inflammatory properties than untreated ADSCs in taurocholate-induced pancreatitis. Mechanistically, poly(I : C)-treated ADSCs showed increased production and secretion of interleukin-10 (IL-10), which demonstrates a potent ability to alleviate inflammatory signaling cascades in acinar cells. Simultaneously, the heightened anti-inflammatory effects of poly(I : C)-treated ADSCs in pancreatitis were associated with the regulation of macrophage classical/alternative transformation, thereby mitigating inflammatory factor-mediated damage to the pancreatic acinar cell. We propose that TLR3 activation by poly(I : C) is an effective strategy to enhance the anti-inflammatory properties of MSCs, which offers a valuable consideration for improving the therapeutic efficacy of MSCs in inflammatory diseases.","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"19 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140199147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Shikonin Induces Glioma Necroptosis, Stemness Decline, and Impedes (Immuno)Proteasome Activity","authors":"Xianyun Qin, Lu Zhang, Jilan Liu, Yan Lu, Fuyao Zhou, Feng Jin","doi":"10.1155/2024/1348269","DOIUrl":"https://doi.org/10.1155/2024/1348269","url":null,"abstract":"Gliomas, the most prevalent primary intracranial tumors, exhibit notable features such as heightened malignancy, rapid recurrence, and elevated mortality rates. Presently, standard therapeutic approaches yield limited curative outcomes. Shikonin, an extract derived from traditional Chinese medicine, demonstrates notable bioactivity against various tumors, including gliomas. This study elucidates Shikonin’s capacity to effectively induce necroptosis in glioma cells, concurrently mitigating glioma stemness, as evidenced by diminished levels of stem cell markers, namely SOX2, CD44, CHI3L1, and CD24. Our findings indicate that Shikonin-induced programed necrosis leads to a downregulation of proteasome activity and a decrease in the expression of immune proteasome subunits PSMB8/9/10 and PSME1/2/3, contributing to the attenuation of stemness in gliomas. This study comprehensively investigates the interplay between (immuno)proteasome dynamics, Shikonin-mediated necroptosis, and the consequential reduction in glioma stemness, both in vitro and in vivo. The discussion extends to the potential of Shikonin as a promising therapeutic agent in the management of gliomas, offering a novel avenue for drug development in this challenging clinical context.","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"16 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140128955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stimulated Human Umbilical Cord Mesenchymal Stem Cells Enhance the Osteogenesis and Cranial Bone Regeneration through IL-32 Mediated P38 Signaling Pathway","authors":"Xiaru Zhang, Ying Zheng, Gang Wang, Yuanlin Liu, Yang Wang, Xueyi Jiang, Yueqing Liang, Xinfeng Zhao, Ping Li, Yi Zhang","doi":"10.1155/2024/6693292","DOIUrl":"https://doi.org/10.1155/2024/6693292","url":null,"abstract":"&lt;i&gt;Objective&lt;/i&gt;. Our previous study found that it could significantly increase the expression of IL32 after stimulating the human umbilical cord mesenchymal stem cells (S-HuMSCs). However, its role on the osteogenesis and cranial bone regeneration is still largely unknown. Here, we investigated the possible mechanism of this effect. &lt;i&gt;Material and Methods&lt;/i&gt;. A series of experiments, including single-cell sequencing, flow cytometry, quantitative real-time polymerase chain reaction, and western blotting, were carried out to evaluate the characteristic and adipogenic–osteogenic differentiation potential of IL-32 overexpression HuMSCs (IL-32&lt;sup&gt;high&lt;/sup&gt;HuMSCs) through mediating the P38 signaling pathway. Moreover, a rat skull bone defect model was established and treated by directly injecting the IL-32&lt;sup&gt;high&lt;/sup&gt;HuMSCs to conduct its role on the cranial bone regeneration. &lt;i&gt;Results&lt;/i&gt;. In total, it found that compared to HuMSCs, IL32 was significantly increased and promoted the osteogenic differentiation (lower expressions of PPAR&lt;i&gt;γ&lt;/i&gt;, Adiponectin, and C/EBP&lt;i&gt;α&lt;/i&gt;, and increased expressions of RUNX2, ALP, BMP2, OPN, SP7, OCN, and DLX5) in the S-HuMSCs (&lt;span&gt;&lt;svg height=\"9.2729pt\" style=\"vertical-align:-0.6370001pt\" version=\"1.1\" viewbox=\"-0.0498162 -8.6359 19.289 9.2729\" width=\"19.289pt\" xmlns=\"http://www.w3.org/2000/svg\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"&gt;&lt;g transform=\"matrix(.013,0,0,-0.013,0,0)\"&gt;&lt;/path&gt;&lt;/g&gt;&lt;g transform=\"matrix(.013,0,0,-0.013,11.658,0)\"&gt;&lt;/path&gt;&lt;/g&gt;&lt;/svg&gt;&lt;span&gt;&lt;/span&gt;&lt;span&gt;&lt;svg height=\"9.2729pt\" style=\"vertical-align:-0.6370001pt\" version=\"1.1\" viewbox=\"22.8711838 -8.6359 21.918 9.2729\" width=\"21.918pt\" xmlns=\"http://www.w3.org/2000/svg\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"&gt;&lt;g transform=\"matrix(.013,0,0,-0.013,22.921,0)\"&gt;&lt;/path&gt;&lt;/g&gt;&lt;g transform=\"matrix(.013,0,0,-0.013,29.161,0)\"&gt;&lt;/path&gt;&lt;/g&gt;&lt;g transform=\"matrix(.013,0,0,-0.013,32.125,0)\"&gt;&lt;use xlink:href=\"#g113-49\"&gt;&lt;/use&gt;&lt;/g&gt;&lt;g transform=\"matrix(.013,0,0,-0.013,38.365,0)\"&gt;&lt;/path&gt;&lt;/g&gt;&lt;/svg&gt;).&lt;/span&gt;&lt;/span&gt; Meanwhile, the enhanced osteogenic differentiation of HuMSCs was recovered by IL-32 overexpression (IL-32&lt;sup&gt;high&lt;/sup&gt;HuMSCs) through activating the P38 signaling pathway, like as the S-HuMSCs (&lt;span&gt;&lt;svg height=\"9.2729pt\" style=\"vertical-align:-0.6370001pt\" version=\"1.1\" viewbox=\"-0.0498162 -8.6359 19.289 9.2729\" width=\"19.289pt\" xmlns=\"http://www.w3.org/2000/svg\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"&gt;&lt;g transform=\"matrix(.013,0,0,-0.013,0,0)\"&gt;&lt;use xlink:href=\"#g113-81\"&gt;&lt;/use&gt;&lt;/g&gt;&lt;g transform=\"matrix(.013,0,0,-0.013,11.658,0)\"&gt;&lt;use xlink:href=\"#g117-91\"&gt;&lt;/use&gt;&lt;/g&gt;&lt;/svg&gt;&lt;span&gt;&lt;/span&gt;&lt;span&gt;&lt;svg height=\"9.2729pt\" style=\"vertical-align:-0.6370001pt\" version=\"1.1\" viewbox=\"22.8711838 -8.6359 21.918 9.2729\" width=\"21.918pt\" xmlns=\"http://www.w3.org/2000/svg\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"&gt;&lt;g transform=\"matrix(.013,0,0,-0.013,22.921,0)\"&gt;&lt;use xlink:href=\"#g113-49\"&gt;&lt;/use&gt;&lt;/g&gt;&lt;g transform=\"matrix(.013,0,0,-0.013,29.161,0)\"&gt;&lt;use xlink:href=","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"116 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140114918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}