Background: Advancement in tissue engineering has provided novel solutions for creating scaffolds as well as applying induction factors in the differentiation of stem cells. The present research aimed to investigate the differentiation of human adipose-derived mesenchymal stem cells to neural-like cells using the novel bioprinting method, as well as the effect of cerebrospinal fluid exosomes.
Methods: In the present study, the extent of neuronal proliferation and differentiation of adipose- derived stem cells were explored using the MTT method, immunocytochemistry, and real-- time PCR in the scaffolds created by the bioprinting process. Furthermore, in order to investigate the veracity of the identity of the CSF (Cerebrospinal fluid) derived exosomes, after the isolation of exosomes, dynamic light scattering (DLS), scanning electron microscopy (SEM), and atomic force microscopy (AFM) techniques were used.
Results: MTT findings indicated survivability and proliferation of cells in the scaffolds created by the bioprinting process during a 14-day period. The results obtained from real-time PCR showed that the level of MAP2 gene (Microtubule Associated Protein 2) expression increased on days 7 and 14, while the expression of the Nestin gene (intermediate filament protein) significantly decreased compared to the control. The investigation to confirm the identity of exosomes indicated that the CSF-derived exosomes had a spherical shape with a 40-100 nm size.
Conclusion: CSF-derived exosomes can contribute to the neuronal differentiation of adipose- derived stem cells in alginate hydrogel scaffolds created by the bioprinting process.
{"title":"Differentiation of Human Adipose-derived Stem Cells to Exosome-affected Neural-like Cells Extracted from Human Cerebrospinal Fluid Using Bioprinting Process.","authors":"Mojtaba Cheravi, Javad Baharara, Parichehreh Yaghmaei, Nasim Hayati Roudbari","doi":"10.2174/011574888X270145231102062259","DOIUrl":"10.2174/011574888X270145231102062259","url":null,"abstract":"<p><strong>Background: </strong>Advancement in tissue engineering has provided novel solutions for creating scaffolds as well as applying induction factors in the differentiation of stem cells. The present research aimed to investigate the differentiation of human adipose-derived mesenchymal stem cells to neural-like cells using the novel bioprinting method, as well as the effect of cerebrospinal fluid exosomes.</p><p><strong>Methods: </strong>In the present study, the extent of neuronal proliferation and differentiation of adipose- derived stem cells were explored using the MTT method, immunocytochemistry, and real-- time PCR in the scaffolds created by the bioprinting process. Furthermore, in order to investigate the veracity of the identity of the CSF (Cerebrospinal fluid) derived exosomes, after the isolation of exosomes, dynamic light scattering (DLS), scanning electron microscopy (SEM), and atomic force microscopy (AFM) techniques were used.</p><p><strong>Results: </strong>MTT findings indicated survivability and proliferation of cells in the scaffolds created by the bioprinting process during a 14-day period. The results obtained from real-time PCR showed that the level of MAP2 gene (Microtubule Associated Protein 2) expression increased on days 7 and 14, while the expression of the Nestin gene (intermediate filament protein) significantly decreased compared to the control. The investigation to confirm the identity of exosomes indicated that the CSF-derived exosomes had a spherical shape with a 40-100 nm size.</p><p><strong>Conclusion: </strong>CSF-derived exosomes can contribute to the neuronal differentiation of adipose- derived stem cells in alginate hydrogel scaffolds created by the bioprinting process.</p>","PeriodicalId":93971,"journal":{"name":"Current stem cell research & therapy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92158083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01DOI: 10.2174/011574888X265623230921045240
Xiangyu Zhang, Xin Zhang, Lu Chen, Jiaqi Zhao, Ashok Raj, Yanping Wang, Shulin Li, Chi Zhang, Jing Yang, Dong Sun
Background: Angiogenesis and energy metabolism mediated by adipose mesenchymal stem cell-derived exosomes (AMSC-exos) are promising therapeutics for vascular diseases.
Objectives: The current study aimed to explore whether AMSC-exos have therapeutic effects on oxygen and glucose deprivation (OGD) human umbilical vein endothelial cells (HUVECs) injury by modulating the SIX1/HBO1 signaling pathway to upregulate endothelial cells (E.C.s) glycolysis and angiogenesis.
Methods: AMSC-exos were isolated and characterized following standard protocols. AMSC-exos cytoprotective effects were evaluated in the HUVECs-OGD model. The proliferation, migration, and tube formation abilities of HUVECs were assessed. The glycolysis level was evaluated by detecting lactate production and ATP synthesis. The expressions of HK2, PKM2, VEGF, HIF-1α, SIX1, and HBO1 were determined by western blotting, and finally, the SIX1 overexpression vector or small interfering RNA (siRNA) was transfected into HUVECs to assess the change in HBO1 expression.
Results: Our study revealed that AMSC-exos promotes E.C.s survival after OGD, reducing E.C.s apoptosis while strengthening E.C.'s angiogenic ability. AMSC-exos enhanced glycolysis and reduced OGD-induced ECs injury by modulation of the SIX1/HBO1 signaling pathway, which is a novel anti-endothelial cell injury role of AMSC-exos that regulates glycolysis via activating the SIX1/HBO1 signaling pathway.
Conclusion: The current study findings demonstrate a useful angiogenic therapeutic strategy for AMSC-exos treatment in vascular injury, thus providing new therapeutic ideas for treating ischaemic diseases.
{"title":"Adipose Mesenchymal Stem Cell-derived Exosomes Enhanced Glycolysis through the SIX1/HBO1 Pathway against Oxygen and Glucose Deprivation Injury in Human Umbilical Vein Endothelial Cells.","authors":"Xiangyu Zhang, Xin Zhang, Lu Chen, Jiaqi Zhao, Ashok Raj, Yanping Wang, Shulin Li, Chi Zhang, Jing Yang, Dong Sun","doi":"10.2174/011574888X265623230921045240","DOIUrl":"10.2174/011574888X265623230921045240","url":null,"abstract":"<p><strong>Background: </strong>Angiogenesis and energy metabolism mediated by adipose mesenchymal stem cell-derived exosomes (AMSC-exos) are promising therapeutics for vascular diseases.</p><p><strong>Objectives: </strong>The current study aimed to explore whether AMSC-exos have therapeutic effects on oxygen and glucose deprivation (OGD) human umbilical vein endothelial cells (HUVECs) injury by modulating the SIX1/HBO1 signaling pathway to upregulate endothelial cells (E.C.s) glycolysis and angiogenesis.</p><p><strong>Methods: </strong>AMSC-exos were isolated and characterized following standard protocols. AMSC-exos cytoprotective effects were evaluated in the HUVECs-OGD model. The proliferation, migration, and tube formation abilities of HUVECs were assessed. The glycolysis level was evaluated by detecting lactate production and ATP synthesis. The expressions of HK2, PKM2, VEGF, HIF-1α, SIX1, and HBO1 were determined by western blotting, and finally, the SIX1 overexpression vector or small interfering RNA (siRNA) was transfected into HUVECs to assess the change in HBO1 expression.</p><p><strong>Results: </strong>Our study revealed that AMSC-exos promotes E.C.s survival after OGD, reducing E.C.s apoptosis while strengthening E.C.'s angiogenic ability. AMSC-exos enhanced glycolysis and reduced OGD-induced ECs injury by modulation of the SIX1/HBO1 signaling pathway, which is a novel anti-endothelial cell injury role of AMSC-exos that regulates glycolysis <i>via</i> activating the SIX1/HBO1 signaling pathway.</p><p><strong>Conclusion: </strong>The current study findings demonstrate a useful angiogenic therapeutic strategy for AMSC-exos treatment in vascular injury, thus providing new therapeutic ideas for treating ischaemic diseases.</p>","PeriodicalId":93971,"journal":{"name":"Current stem cell research & therapy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41163269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01DOI: 10.2174/011574888X260261230928094309
Yuanyuan Sun, Cuie Chen, Yuanyuan Liu, Anqun Sheng, Shi Wang, Xixi Zhang, Dan Wang, Qiu Wang, Chaosheng Lu, Zhenlang Lin
Background: Mesenchymal stem cell-derived exosomes (MSC-Exos) therapies have shown prospects in preclinical models of pathologies relevant to neonatal medicine, such as bronchopulmonary dysplasia (BPD). Adipose-derived stem cells (ADSCs) have been recognized as one of the most promising stem cell sources. Autophagy plays a key role in regulating intracellular conditions, maintaining cell growth and development, and participating in the pathogenesis of BPD.
Objectives: To investigate the potential therapeutic role of ADSC-Exos on BPD and to illustrate the role of autophagy in this process.
Method: ADSC-Exos was isolated from media conditioned of ADSCs by ultracentrifugation and characterized by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and Western blotting (WB). Newborn rats were exposed to hyperoxia (90% O2) from postnatal day 0 (P0) to P7, and returned to room air until P14 to mimic BPD. ADSC-Exos was treated by intratracheal or intravenous administration on P4. Treated animals and appropriate controls were harvested on P7 and P14 for assessment of pulmonary parameters.
Results: Hyperoxia-exposed rats were presented with pronounced alveolar simplification with decreased radial alveolar count (RAC) and increased mean linear intercept (MLI), impaired vascular development with low vascular endothelial growth factor (VEGF) and CD31 expression, and stimulated inflammation with increased expression of TNF-α, IL-1β, and IL-6, and decreased expression of IL-10. Meanwhile, the rats with hyperoxia exposure blocked autophagic flux with lower levels of Beclin1, LC3B, LC3BII/I ratio and higher levels of p62. ADSC-Exos administration protected the neonatal lung tissues from the hyperoxia-induced arrest of alveolar and vascular development, reduced inflammation, and facilitated autophagy. Intratracheal administration was more efficacious than intravenous administration.
Conclusion: The intratracheal administration of ADSC-Exos significantly improved alveolarization and pulmonary vascularization arrest in hyperoxia-induced BPD, which was associated with facilitating autophagy in part.
{"title":"Adipose Stem Cells Derived Exosomes Alleviate Bronchopulmonary Dysplasia and Regulate Autophagy in Neonatal Rats.","authors":"Yuanyuan Sun, Cuie Chen, Yuanyuan Liu, Anqun Sheng, Shi Wang, Xixi Zhang, Dan Wang, Qiu Wang, Chaosheng Lu, Zhenlang Lin","doi":"10.2174/011574888X260261230928094309","DOIUrl":"10.2174/011574888X260261230928094309","url":null,"abstract":"<p><strong>Background: </strong>Mesenchymal stem cell-derived exosomes (MSC-Exos) therapies have shown prospects in preclinical models of pathologies relevant to neonatal medicine, such as bronchopulmonary dysplasia (BPD). Adipose-derived stem cells (ADSCs) have been recognized as one of the most promising stem cell sources. Autophagy plays a key role in regulating intracellular conditions, maintaining cell growth and development, and participating in the pathogenesis of BPD.</p><p><strong>Objectives: </strong>To investigate the potential therapeutic role of ADSC-Exos on BPD and to illustrate the role of autophagy in this process.</p><p><strong>Method: </strong>ADSC-Exos was isolated from media conditioned of ADSCs by ultracentrifugation and characterized by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and Western blotting (WB). Newborn rats were exposed to hyperoxia (90% O2) from postnatal day 0 (P0) to P7, and returned to room air until P14 to mimic BPD. ADSC-Exos was treated by intratracheal or intravenous administration on P4. Treated animals and appropriate controls were harvested on P7 and P14 for assessment of pulmonary parameters.</p><p><strong>Results: </strong>Hyperoxia-exposed rats were presented with pronounced alveolar simplification with decreased radial alveolar count (RAC) and increased mean linear intercept (MLI), impaired vascular development with low vascular endothelial growth factor (VEGF) and CD31 expression, and stimulated inflammation with increased expression of TNF-α, IL-1β, and IL-6, and decreased expression of IL-10. Meanwhile, the rats with hyperoxia exposure blocked autophagic flux with lower levels of Beclin1, LC3B, LC3BII/I ratio and higher levels of p62. ADSC-Exos administration protected the neonatal lung tissues from the hyperoxia-induced arrest of alveolar and vascular development, reduced inflammation, and facilitated autophagy. Intratracheal administration was more efficacious than intravenous administration.</p><p><strong>Conclusion: </strong>The intratracheal administration of ADSC-Exos significantly improved alveolarization and pulmonary vascularization arrest in hyperoxia-induced BPD, which was associated with facilitating autophagy in part.</p>","PeriodicalId":93971,"journal":{"name":"Current stem cell research & therapy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41223904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01DOI: 10.2174/011574888X260032230925052240
Elham Zendedel, Lobat Tayebi, Mohammad Nikbakht, Elham Hasanzadeh, Shiva Asadpour
Mesenchymal Stem Cells (MSCs) are being investigated as a treatment for a novel viral disease owing to their immunomodulatory, anti-inflammatory, tissue repair and regeneration characteristics, however, the exact processes are unknown. MSC therapy was found to be effective in lowering immune system overactivation and increasing endogenous healing after SARS-CoV-2 infection by improving the pulmonary microenvironment. Many studies on mesenchymal stem cells have been undertaken concurrently, and we may help speed up the effectiveness of these studies by collecting and statistically analyzing data from them. Based on clinical trial information found on clinicaltrials. gov and on 16 November 2020, which includes 63 clinical trials in the field of patient treatment with COVID-19 using MSCs, according to the trend of increasing studies in this field, and with the help of meta-analysis studies, it is possible to hope that the promise of MSCs will one day be realized. The potential therapeutic applications of MSCs for COVID-19 are investigated in this study.
{"title":"Clinical Trials of Mesenchymal Stem Cells for the Treatment of COVID 19.","authors":"Elham Zendedel, Lobat Tayebi, Mohammad Nikbakht, Elham Hasanzadeh, Shiva Asadpour","doi":"10.2174/011574888X260032230925052240","DOIUrl":"10.2174/011574888X260032230925052240","url":null,"abstract":"<p><p>Mesenchymal Stem Cells (MSCs) are being investigated as a treatment for a novel viral disease owing to their immunomodulatory, anti-inflammatory, tissue repair and regeneration characteristics, however, the exact processes are unknown. MSC therapy was found to be effective in lowering immune system overactivation and increasing endogenous healing after SARS-CoV-2 infection by improving the pulmonary microenvironment. Many studies on mesenchymal stem cells have been undertaken concurrently, and we may help speed up the effectiveness of these studies by collecting and statistically analyzing data from them. Based on clinical trial information found on clinicaltrials. gov and on 16 November 2020, which includes 63 clinical trials in the field of patient treatment with COVID-19 using MSCs, according to the trend of increasing studies in this field, and with the help of meta-analysis studies, it is possible to hope that the promise of MSCs will one day be realized. The potential therapeutic applications of MSCs for COVID-19 are investigated in this study.</p>","PeriodicalId":93971,"journal":{"name":"Current stem cell research & therapy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41184575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01DOI: 10.2174/011574888X311270240319084835
Fan Zhang, Leisheng Zhang, Hao Yu
Exosomes secreted by mesenchymal stem/stromal cells (MSC-Exos) are advantageous candidate sources for novel acellular therapy. Despite the current standards of good manufacturing practice (GMP), the deficiency of suitable quality-control methods and the difficulties in large-scale preparation largely restrict the development of therapeutic products and their clinical applications worldwide. Herein, we mainly focus on three dominating issues commonly encountered in exosomal GMP, including issues upstream of the cell culture process, downstream of the purification process, exosomes quality control, and the drug properties of exosomes and their druggability from a corporate perspective. Collectively, in this review article, we put forward the issues of preparing clinical exosome drugs for the treatment of diverse diseases and provide new references for the clinical application of GMP-grade MSC-Exos.
{"title":"Potential Druggability of Mesenchymal Stem/Stromal Cell-derived Exosomes.","authors":"Fan Zhang, Leisheng Zhang, Hao Yu","doi":"10.2174/011574888X311270240319084835","DOIUrl":"10.2174/011574888X311270240319084835","url":null,"abstract":"<p><p>Exosomes secreted by mesenchymal stem/stromal cells (MSC-Exos) are advantageous candidate sources for novel acellular therapy. Despite the current standards of good manufacturing practice (GMP), the deficiency of suitable quality-control methods and the difficulties in large-scale preparation largely restrict the development of therapeutic products and their clinical applications worldwide. Herein, we mainly focus on three dominating issues commonly encountered in exosomal GMP, including issues upstream of the cell culture process, downstream of the purification process, exosomes quality control, and the drug properties of exosomes and their druggability from a corporate perspective. Collectively, in this review article, we put forward the issues of preparing clinical exosome drugs for the treatment of diverse diseases and provide new references for the clinical application of GMP-grade MSC-Exos.</p>","PeriodicalId":93971,"journal":{"name":"Current stem cell research & therapy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140208684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Inflammatory bowel disease (IBD) is a global health problem in which gut microbiota dysbiosis plays a pivotal pathogenic role. Mesenchymal stem cells (MSCs) therapy has shown promising application prospects for its powerful immune regulation and tissue repair ability. Recent experimental data suggest that MSCs also regulate the composition of gut microbiota. The current review analyzed, for the first time, the research data linking MSCs and gut microbiota modulation in IBD models aiming at assessing the role of gut microbiota in MSCs repair of IBD.
Methods: A comprehensive and structured literature search was performed up to January 2023 on the PubMed, Web of Science, and Scopus databases. The quality and risk of bias assessment followed the PRISMA guidelines and SYRCLE's tool.
Results: A total of nine pre-clinical studies on animal models were included. Although the dose and route of MSCs applied were quite heterogeneous, results showed that MSCs displayed protective effects on intestinal inflammation, including mice general assessment, immunoregulation, and intestinal barrier integrity. Meanwhile, studies showed positive effects on the composition of gut flora with MSCs administration, which had been characterized by restoration of Firmicutes/ Bacteroides balance and reduction of Proteobacteria. The beneficial bacteria Akkermansia, Bifidobacterium, and Lactobacillus were also distinctly enriched, and the pathogenic bacteria Escherichia-Shigella was conversely decreased. The alpha and beta diversity were also regulated to resemble those of healthy mice. Microbial metabolic functions, such as biosynthesis of secondary bile acid and sphingolipid metabolism, and some biological behaviors related to cell regeneration were also up-regulated, while cancer function and poorly characterized cellular function were down-regulated.
Conclusion: Current data support the remodeling effect on gut microbiota with MSC administration, which provides a potential therapeutic mechanism for MSCs in the treatment of IBD. Additional studies in humans and animal models are warranted to further confirm the role of gut microflora in MSCs repairing IBD.
背景:炎症性肠病(IBD)是一个全球性的健康问题,肠道微生物群失调在其中起着关键的致病作用。间充质干细胞以其强大的免疫调节和组织修复能力显示出良好的应用前景。最近的实验数据表明,间充质干细胞还调节肠道微生物群的组成。本综述首次分析了IBD模型中MSCs和肠道微生物群调节之间的研究数据,旨在评估肠道微生物群在MSCs修复IBD中的作用。方法:截至2023年1月,在PubMed、Web of Science和Scopus数据库上进行了全面、结构化的文献检索。偏差评估的质量和风险遵循PRISMA指南和SYRCLE的工具。结果:共纳入9项关于动物模型的临床前研究。尽管MSCs的应用剂量和途径非常不同,但结果表明MSCs对肠道炎症表现出保护作用,包括小鼠的一般评估、免疫调节和肠道屏障完整性。同时,研究表明,MSC给药对肠道菌群组成有积极影响,其特征是恢复厚壁菌门/拟杆菌门的平衡和减少变形菌。有益细菌阿克曼菌、双歧杆菌和乳酸杆菌也明显富集,致病菌志贺氏杆菌则相反减少。α和β多样性也被调节为与健康小鼠相似。微生物代谢功能,如次级胆汁酸的生物合成和鞘脂代谢,以及一些与细胞再生有关的生物行为也上调,而癌症功能和特征较差的细胞功能下调。结论:目前的数据支持MSC给药对肠道微生物群的重塑作用,这为MSC治疗IBD提供了潜在的治疗机制。有必要在人类和动物模型中进行更多的研究,以进一步证实肠道菌群在MSCs修复IBD中的作用。
{"title":"Impact of Mesenchymal Stem Cells on the Gut Microbiota and Microbiota Associated Functions in Inflammatory Bowel Disease: A Systematic Review of Preclinical Evidence on Animal Models.","authors":"Airu Liu, Chenyang Li, Chen Wang, Xiaonan Liang, Xiaolan Zhang","doi":"10.2174/011574888X250413230920051715","DOIUrl":"10.2174/011574888X250413230920051715","url":null,"abstract":"<p><strong>Background: </strong>Inflammatory bowel disease (IBD) is a global health problem in which gut microbiota dysbiosis plays a pivotal pathogenic role. Mesenchymal stem cells (MSCs) therapy has shown promising application prospects for its powerful immune regulation and tissue repair ability. Recent experimental data suggest that MSCs also regulate the composition of gut microbiota. The current review analyzed, for the first time, the research data linking MSCs and gut microbiota modulation in IBD models aiming at assessing the role of gut microbiota in MSCs repair of IBD.</p><p><strong>Methods: </strong>A comprehensive and structured literature search was performed up to January 2023 on the PubMed, Web of Science, and Scopus databases. The quality and risk of bias assessment followed the PRISMA guidelines and SYRCLE's tool.</p><p><strong>Results: </strong>A total of nine pre-clinical studies on animal models were included. Although the dose and route of MSCs applied were quite heterogeneous, results showed that MSCs displayed protective effects on intestinal inflammation, including mice general assessment, immunoregulation, and intestinal barrier integrity. Meanwhile, studies showed positive effects on the composition of gut flora with MSCs administration, which had been characterized by restoration of <i>Firmicutes/ Bacteroides</i> balance and reduction of <i>Proteobacteria.</i> The beneficial bacteria <i>Akkermansia, Bifidobacterium,</i> and <i>Lactobacillus</i> were also distinctly enriched, and the pathogenic bacteria <i>Escherichia-Shigella</i> was conversely decreased. The alpha and beta diversity were also regulated to resemble those of healthy mice. Microbial metabolic functions, such as biosynthesis of secondary bile acid and sphingolipid metabolism, and some biological behaviors related to cell regeneration were also up-regulated, while cancer function and poorly characterized cellular function were down-regulated.</p><p><strong>Conclusion: </strong>Current data support the remodeling effect on gut microbiota with MSC administration, which provides a potential therapeutic mechanism for MSCs in the treatment of IBD. Additional studies in humans and animal models are warranted to further confirm the role of gut microflora in MSCs repairing IBD.</p>","PeriodicalId":93971,"journal":{"name":"Current stem cell research & therapy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41223906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01DOI: 10.2174/011574888X259932231010112521
Yingxue Yang, Yuan Yuan, Boning Xia
Backgrounds: Gastric cancer (GC) is threatening public health, with at least one million new cases reported each year. Rhomboid domain-containing protein 1 (RHBDD1) has been identified to regulate the proliferation, migration, and metastasis of cancer cells. However, the role of RHBDD1 in GC has not been elucidated.
Objects: This study aimed to investigate the role of RHBDD1 on the growth, metastasis, and stemness characteristics of GC.
Methods: RHBDD1 expression was analyzed from the TCGA databank. qRT-PCR was conducted to evaluate the transcription level of RHBDD1. Western blots were used to evaluate the protein expression of RHBDD1, CD133, CD44, Nanog, β-catenin and c-myc. Colony formation assay and transwell assay were conducted to evaluate the growth and metastasis of NCI-N87 cells, respectively. Sphere-forming assay was performed to study the stemness characteristics. The nude mice xenotransplantation model and immunohistochemistry (IHC) were performed to evaluate the growth of GC in vivo. Results: RHBDD1 expression is elevated in GC cells and clinical tissues. RHBDD1 expression is positively associated with cell proliferation and metastasis of GC cells. RHBDD1 knockdown suppresses the expression of CD133, CD44 and Nanog and attenuates sphere-forming ability. RHBDD1 activates the Wnt/β-catenin pathway via promoting the expression of β-catenin / c-myc and inducing β-catenin translocation into nuclear. RHBDD1 knockdown inhibits the growth of GC in nude mice xenotransplantation model.
Conclusion: RHBDD1 is highly expressed in GC, and its knockdown inhibits the growth, metastasis and stemness characteristics of GC cells through activating the Wnt/β-catenin pathway, suggesting that RHBDD1 has the potential to be a novel therapeutic target for GC treatment.
{"title":"RHBDD1 Promotes the Growth and Stemness Characteristics of Gastric Cancer Cells by Activating Wnt/β-catenin Signaling Pathway.","authors":"Yingxue Yang, Yuan Yuan, Boning Xia","doi":"10.2174/011574888X259932231010112521","DOIUrl":"10.2174/011574888X259932231010112521","url":null,"abstract":"<p><strong>Backgrounds: </strong>Gastric cancer (GC) is threatening public health, with at least one million new cases reported each year. Rhomboid domain-containing protein 1 (RHBDD1) has been identified to regulate the proliferation, migration, and metastasis of cancer cells. However, the role of RHBDD1 in GC has not been elucidated.</p><p><strong>Objects: </strong>This study aimed to investigate the role of RHBDD1 on the growth, metastasis, and stemness characteristics of GC.</p><p><strong>Methods: </strong>RHBDD1 expression was analyzed from the TCGA databank. qRT-PCR was conducted to evaluate the transcription level of RHBDD1. Western blots were used to evaluate the protein expression of RHBDD1, CD133, CD44, Nanog, β-catenin and c-myc. Colony formation assay and transwell assay were conducted to evaluate the growth and metastasis of NCI-N87 cells, respectively. Sphere-forming assay was performed to study the stemness characteristics. The nude mice xenotransplantation model and immunohistochemistry (IHC) were performed to evaluate the growth of GC <i>in vivo.</i> Results: RHBDD1 expression is elevated in GC cells and clinical tissues. RHBDD1 expression is positively associated with cell proliferation and metastasis of GC cells. RHBDD1 knockdown suppresses the expression of CD133, CD44 and Nanog and attenuates sphere-forming ability. RHBDD1 activates the Wnt/β-catenin pathway <i>via</i> promoting the expression of β-catenin / c-myc and inducing β-catenin translocation into nuclear. RHBDD1 knockdown inhibits the growth of GC in nude mice xenotransplantation model.</p><p><strong>Conclusion: </strong>RHBDD1 is highly expressed in GC, and its knockdown inhibits the growth, metastasis and stemness characteristics of GC cells through activating the Wnt/β-catenin pathway, suggesting that RHBDD1 has the potential to be a novel therapeutic target for GC treatment.</p>","PeriodicalId":93971,"journal":{"name":"Current stem cell research & therapy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49686498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01DOI: 10.2174/011574888X252482230926104342
Mansoor Khaledi, Bita Zandi, Zeinab Mohsenipour
Wound infection often requires a long period of care and an onerous treatment process. Also, the rich environment makes the wound an ideal niche for microbial growth. Stable structures, like biofilm, and drug-resistant strains cause a delay in the healing process, which has become one of the important challenges in wound treatment. Many studies have focused on alternative methods to deal the wound infections. One of the novel and highly potential ways is mesenchymal stromal cells (MSCs). MSCs are mesoderm-derived pluripotent adult stem cells with the capacity for self-renewal, multidirectional differentiation, and immunological control. Also, MSCs have anti-inflammatory and antiapoptotic effects. MScs, as pluripotent stromal cells, differentiate into many mature cells. Also, MSCs produce antimicrobial compounds, such as antimicrobial peptides (AMP), as well as secrete immune modulators, which are two basic features considered in wound healing. Despite the advantages, preserving the structure and activity of MSCs is considered one of the most important points in the treatment. MSCs' antimicrobial effects on microorganisms involved in wound infection have been confirmed in various studies. In this review, we aimed to discuss the antimicrobial and therapeutic applications of MSCs in the infected wound healing processes.
{"title":"The Effect of Mesenchymal Stem Cells on the Wound Infection.","authors":"Mansoor Khaledi, Bita Zandi, Zeinab Mohsenipour","doi":"10.2174/011574888X252482230926104342","DOIUrl":"10.2174/011574888X252482230926104342","url":null,"abstract":"<p><p>Wound infection often requires a long period of care and an onerous treatment process. Also, the rich environment makes the wound an ideal niche for microbial growth. Stable structures, like biofilm, and drug-resistant strains cause a delay in the healing process, which has become one of the important challenges in wound treatment. Many studies have focused on alternative methods to deal the wound infections. One of the novel and highly potential ways is mesenchymal stromal cells (MSCs). MSCs are mesoderm-derived pluripotent adult stem cells with the capacity for self-renewal, multidirectional differentiation, and immunological control. Also, MSCs have anti-inflammatory and antiapoptotic effects. MScs, as pluripotent stromal cells, differentiate into many mature cells. Also, MSCs produce antimicrobial compounds, such as antimicrobial peptides (AMP), as well as secrete immune modulators, which are two basic features considered in wound healing. Despite the advantages, preserving the structure and activity of MSCs is considered one of the most important points in the treatment. MSCs' antimicrobial effects on microorganisms involved in wound infection have been confirmed in various studies. In this review, we aimed to discuss the antimicrobial and therapeutic applications of MSCs in the infected wound healing processes.</p>","PeriodicalId":93971,"journal":{"name":"Current stem cell research & therapy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41184577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Umbilical cord mesenchymal stem cells (UC-MSCs) are increasingly being utilized for immune-related disease therapies due to their low immunogenicity. However, the primary culture of UC-MSCs requires the supplementation of serum in the growth medium, which has posed a challenge due to ethical issues related to the collection method of the fetal bovine serum (FBS) that is routinely used in cell culture.
Aim: In order to address this, the purpose of this research was to assess the effectiveness of adult bovine serum (ABS) as a different and more affordable source of serum for the in-vitro cultivation of UC-MSCs. UC-MSCs were isolated from the umbilical cord of Wharton's jelly of cow immediately after birth, by digestion with Collagenase type I.
Method: ABS was collected from fresh bovine sources and heat-inactivated. The morphology of UC-MSCs was observed under an inverted microscope, and growth patterns, proliferative index, and doubling time were calculated every two days to compare the efficacy of ABS with FBS. Immunocytochemistry for specific markers was also conducted on the MSCs.
Result: The results showed a notable difference in morphology, growth rate, population doubling, and proliferative index between ABS and FBS.
Conclusion: Intriguingly, ABS proved to be an effective supplement in the growth medium for expanding UC-MSCs in vitro, providing a viable alternative to FBS.
{"title":"<i>In-vitro</i> Augmentation of Mesenchymal Stem Cells by Using Adult Bovine Serum.","authors":"Somia Shehzadi, Maryam Javed, Asmat Ullah, Ahmad Bilal Waqar, Fatima Iftikhar Shah, Sajjad Ullah","doi":"10.2174/011574888X260118230927050143","DOIUrl":"10.2174/011574888X260118230927050143","url":null,"abstract":"<p><strong>Background: </strong>Umbilical cord mesenchymal stem cells (UC-MSCs) are increasingly being utilized for immune-related disease therapies due to their low immunogenicity. However, the primary culture of UC-MSCs requires the supplementation of serum in the growth medium, which has posed a challenge due to ethical issues related to the collection method of the fetal bovine serum (FBS) that is routinely used in cell culture.</p><p><strong>Aim: </strong>In order to address this, the purpose of this research was to assess the effectiveness of adult bovine serum (ABS) as a different and more affordable source of serum for the in-vitro cultivation of UC-MSCs. UC-MSCs were isolated from the umbilical cord of Wharton's jelly of cow immediately after birth, by digestion with Collagenase type I.</p><p><strong>Method: </strong>ABS was collected from fresh bovine sources and heat-inactivated. The morphology of UC-MSCs was observed under an inverted microscope, and growth patterns, proliferative index, and doubling time were calculated every two days to compare the efficacy of ABS with FBS. Immunocytochemistry for specific markers was also conducted on the MSCs.</p><p><strong>Result: </strong>The results showed a notable difference in morphology, growth rate, population doubling, and proliferative index between ABS and FBS.</p><p><strong>Conclusion: </strong>Intriguingly, ABS proved to be an effective supplement in the growth medium for expanding UC-MSCs <i>in vitro</i>, providing a viable alternative to FBS.</p>","PeriodicalId":93971,"journal":{"name":"Current stem cell research & therapy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49686497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Aging is a biological and gradual deterioration of function in living organisms. Aging is one of the risk factors for heart disease.
Objective: Although mesenchymal stem cell transplantation shows potential in heart disease treatment, the relationship between stem cell-based therapy and oxidative stress/inflammasome axis regulation remains unclear. This study hypothesized that intervention of stem cells showed a protective effect on heart aging induced by D-galactose through regulation of oxidative stress/inflammasome axis.
Methods: An aging animal model was designed to test the above hypothesis. Experimental animals were divided into three groups, including Sham, D-gal (aging rats induced by d-galactose), and D-gal+WJSC (aging rats receiving mesenchymal stem cells).
Results: Compared to the Sham, the experimental results indicate that structural alteration (HE stain and Masson's Trichrome stain), oxidative stress elevation (increase of TBARS level, expression of gp-91 and suppression of Sirt-1 as well as SOD2), increase of aging marker p53, suppression of cardiogenesis marker Troponin T, and inflammasome related protein markers expression (NLRP3, caspase-1 and IL-1 beta) were significantly observed in D-gal. In contrast, all pathological pathways were significantly improved in D-gal+WJSC when compared to D-gal. In addition, migration of stem cells to aging heart tissues was observed in the D-gal+WJSC group.
Conclusion: These findings suggest that mesenchymal stem cell transplantation effectively ameliorates aging hearts through oxidative stress/inflammasome axis regulation. The results from this study provide clinical potential for stem cell-based therapy in the treatment of aging hearts.
{"title":"Regulation of ROS/inflammasome Axis is Essential for Cardiac Regeneration in Aging Rats Receiving Transplantation of Mesenchymal Stem Cells.","authors":"Wei-Syun Hu, Jing-Yi Chen, Wei-Yu Liao, Chin-Hsien Chang, Tung-Sheng Chen","doi":"10.2174/011574888X276612231121065203","DOIUrl":"https://doi.org/10.2174/011574888X276612231121065203","url":null,"abstract":"<p><strong>Background: </strong>Aging is a biological and gradual deterioration of function in living organisms. Aging is one of the risk factors for heart disease.</p><p><strong>Objective: </strong>Although mesenchymal stem cell transplantation shows potential in heart disease treatment, the relationship between stem cell-based therapy and oxidative stress/inflammasome axis regulation remains unclear. This study hypothesized that intervention of stem cells showed a protective effect on heart aging induced by D-galactose through regulation of oxidative stress/inflammasome axis.</p><p><strong>Methods: </strong>An aging animal model was designed to test the above hypothesis. Experimental animals were divided into three groups, including Sham, D-gal (aging rats induced by d-galactose), and D-gal+WJSC (aging rats receiving mesenchymal stem cells).</p><p><strong>Results: </strong>Compared to the Sham, the experimental results indicate that structural alteration (HE stain and Masson's Trichrome stain), oxidative stress elevation (increase of TBARS level, expression of gp-91 and suppression of Sirt-1 as well as SOD2), increase of aging marker p53, suppression of cardiogenesis marker Troponin T, and inflammasome related protein markers expression (NLRP3, caspase-1 and IL-1 beta) were significantly observed in D-gal. In contrast, all pathological pathways were significantly improved in D-gal+WJSC when compared to D-gal. In addition, migration of stem cells to aging heart tissues was observed in the D-gal+WJSC group.</p><p><strong>Conclusion: </strong>These findings suggest that mesenchymal stem cell transplantation effectively ameliorates aging hearts through oxidative stress/inflammasome axis regulation. The results from this study provide clinical potential for stem cell-based therapy in the treatment of aging hearts.</p>","PeriodicalId":93971,"journal":{"name":"Current stem cell research & therapy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138465169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}