Qi Xin Ding, Xu Wang, Tian Shu Li, Yue Fang Li, Wan Yue Li, Jia Huan Gao, Yu Rong Liu, WeiSheng Zhuang
<i>Background</i>. Joint articular injection of mesenchymal stem cells (MSCs) has emerged as a novel treatment approach for osteoarthritis (OA). However, the effectiveness of MSCs derived from different sources in treating OA patients remains unclear. Therefore, this study aimed to explore the differences between the effectiveness and safety of different sources of MSCs. <i>Materials and Methods</i>. For inclusion consideration, we searched trial registries and published databases, including PubMed, Cochrane Library, Embase, and Web of Science databases. Revman (V5.3), STATA (V16.0), and R (V4.0) were utilized for conducting data analysis, while the Cochrane Risk of Bias Tool was employed for assessing the quality of the studies. We derived outcome measures at 6 and 12 months based on the duration of study follow-up, including visual analog scale (VAS) score, WOMAC score, WOMAC pain, WOMAC Functional Limitation, and WOMAC stiffness. The evaluation time for short-term effectiveness is set at 6 months, while 12 months is utilized as the longest follow-up time for most studies to assess long-term effectiveness. <i>Results</i>. The evaluation of literature quality showed that the included studies had excellent methodological quality. A meta-analysis revealed that different sources of MSCs improved knee function and pain more effectively among patients suffering from knee OA (KOA) than controls. The results of the network meta-analysis showed the following: short-term functional improvement (the indexes were evaluated after 6 months of follow-up) (WOMAC total score: bone marrow-derived MSC (BMMSC) vs. adipose-derived MSC (ADMSC) (mean difference (MD) = −20.12, 95% confidence interval (CI) −125.24 to 42.88), umbilical cord-derived MSC (UCMSC) (MD = −7.81, 95% CI −158.13 to 74.99); WOMAC stiffness: BMMSC vs. ADMSC (MD = −0.51, 95% CI −7.27 to 4.29), UCMSC (MD = −0.75, 95% CI −9.74 to 6.63); WOMAC functional limitation: BMMSC vs. ADMSC (MD = −12.22, 95% CI −35.05 to 18.86), UCMSC (MD = −9.31, 95% CI −44.26 to 35.27)). Long-term functional improvement (the indexes were evaluated after 12 months of follow-up) (WOMAC total: BMMSC vs. ADMSC (MD = −176.77, 95% CI −757.1 to 378.25), UCMSC (MD = −181.55, 95% CI −937.83 to 541.13); WOMAC stiffness: BMMSC vs. ADMSC (MD = −0.5, 95% CI −26.05 to 18.61), UCMSC (MD = −1.03, 95% CI −30.44 to 21.69); WOMAC functional limitation: BMMSC vs. ADMSC (MD = −5.18, 95% CI −316.72 to 177.1), UCMSC (MD = −8.33, 95% CI −358.78 to 218.76)). Short-term pain relief (the indexes were evaluated after 6 months of follow-up) (VAS score: UCMSC vs. BMMSC (MD = −10.92, 95% CI −31.79 to 12.03), ADMSC (MD = −14.02, 95% CI −36.01 to 9.81), PLMSC (MD = −17.09, 95% CI −46.31 to 13.17); WOMAC pain relief: BMMSC vs. ADMSC (MD = −11.42, 95% CI −39.52 to 11.77), UCMSC (MD = −6.73, 95% CI −47.36 to 29.15)). Long-term pain relief (the indexes were evaluated after 12 months of follow-up) (VAS score: BMMSC vs. UCMSC (MD = −4.33, 95% CI −36.81 to 27.08)
背景。关节注射间充质干细胞（MSCs）已成为治疗骨关节炎（OA）的一种新方法。然而，不同来源的间充质干细胞对治疗OA患者的有效性仍不明确。因此，本研究旨在探讨不同来源间充质干细胞的有效性和安全性之间的差异。材料与方法。出于纳入考虑，我们检索了试验登记和已发表的数据库，包括 PubMed、Cochrane Library、Embase 和 Web of Science 数据库。我们使用 Revman (V5.3)、STATA (V16.0) 和 R (V4.0) 进行数据分析，并使用 Cochrane 偏倚风险工具评估研究质量。我们根据研究的随访时间得出了 6 个月和 12 个月的结果指标，包括视觉模拟量表 (VAS) 评分、WOMAC 评分、WOMAC 疼痛、WOMAC 功能限制和 WOMAC 僵硬度。短期疗效的评估时间定为 6 个月，而 12 个月是大多数研究评估长期疗效的最长随访时间。结果。对文献质量的评估显示，纳入的研究在方法学方面质量上乘。荟萃分析显示，与对照组相比，不同来源的间充质干细胞能更有效地改善膝关节 OA（KOA）患者的膝关节功能和疼痛。网络荟萃分析结果显示：短期功能改善（随访6个月后评估各项指标）（WOMAC总分：骨髓间充质干细胞（BMMSC） vs. 脂肪间充质干细胞（ADMSC）（平均差异（MD）= -20.12，95% 置信区间（CI）-125.24 至 42.88），脐带间充质干细胞（UCMSC）（MD = -7.81，95% CI -158.13 至 74.99）；WOMAC僵硬度：BMMSC vs. ADMSC（MD = -0.51，95% CI -7.27至4.29），UCMSC（MD = -0.75，95% CI -9.74至6.63）；WOMAC功能限制：BMMSC vs. ADMSC (MD = -12.22, 95% CI -35.05 to 18.86), UCMSC (MD = -9.31, 95% CI -44.26 to 35.27))。BMMSC vs. ADMSC（MD = -0.5，95% CI -26.05至18.61），UCMSC（MD =-1.03，95% CI -30.44至21.69）；WOMAC功能限制：BMMSC vs. ADMSC (MD = -5.18, 95% CI -316.72 to 177.1), UCMSC (MD = -8.33, 95% CI -358.78 to 218.76))。短期疼痛缓解情况（随访 6 个月后对各项指标进行评估）（VAS 评分：UCMSC vs. BMMSC，MD=-316.72 vs. 177.1）：UCMSC vs. BMMSC（MD = -10.92，95% CI -31.79 to 12.03），ADMSC（MD = -14.02，95% CI -36.01 to 9.81），PLMSC（MD = -17.09，95% CI -46.31 to 13.17）；WOMAC 疼痛缓解：BMMSC vs. ADMSC (MD = -11.42, 95% CI -39.52 to 11.77), UCMSC (MD = -6.73, 95% CI -47.36 to 29.15))。长期疼痛缓解（随访12个月后评估各项指标）（VAS评分：BMMSC vs. UCMSC（MD = -4.33，95% CI -36.81 to 27.08），ADMSC（MD = -11.43，95% CI -37.5 to 13.42）；WOMAC疼痛缓解：UCMSC vs. ADMSC（MD = 0.23，95% CI -37.87 to 38.11），BMMSC（MD = 5.89，95% CI -25.39 to 51.41））。根据 GRADE 评分系统，WOMAC、VAS 和 AE 评分的质量较低。结论Meta分析表明，与对照组相比，间充质干细胞能有效治疗KOA，改善疼痛和膝关节功能。就 KOA 患者的功能改善而言，短期（6 个月随访）和长期（12 个月随访）结果均表明，虽然大多数治疗方法之间的差异并无统计学意义，但骨髓间充质干细胞可能比其他来源的间充质干细胞更具优势。此外，在缓解 KOA 患者疼痛方面，BM-间充质干细胞和 UC-间充质干细胞可能比 ADMSCs 更有优势，但大多数研究之间的差异并无统计学意义。因此，这项研究表明，BM-间充质干细胞可能比其他来源的间充质干细胞更具临床优势。
{"title":"Comparative Analysis of Short-Term and Long-Term Clinical Efficacy of Mesenchymal Stem Cells from Different Sources in Knee Osteoarthritis: A Network Meta-Analysis","authors":"Qi Xin Ding, Xu Wang, Tian Shu Li, Yue Fang Li, Wan Yue Li, Jia Huan Gao, Yu Rong Liu, WeiSheng Zhuang","doi":"10.1155/2024/2741681","DOIUrl":"https://doi.org/10.1155/2024/2741681","url":null,"abstract":"<i>Background</i>. Joint articular injection of mesenchymal stem cells (MSCs) has emerged as a novel treatment approach for osteoarthritis (OA). However, the effectiveness of MSCs derived from different sources in treating OA patients remains unclear. Therefore, this study aimed to explore the differences between the effectiveness and safety of different sources of MSCs. <i>Materials and Methods</i>. For inclusion consideration, we searched trial registries and published databases, including PubMed, Cochrane Library, Embase, and Web of Science databases. Revman (V5.3), STATA (V16.0), and R (V4.0) were utilized for conducting data analysis, while the Cochrane Risk of Bias Tool was employed for assessing the quality of the studies. We derived outcome measures at 6 and 12 months based on the duration of study follow-up, including visual analog scale (VAS) score, WOMAC score, WOMAC pain, WOMAC Functional Limitation, and WOMAC stiffness. The evaluation time for short-term effectiveness is set at 6 months, while 12 months is utilized as the longest follow-up time for most studies to assess long-term effectiveness. <i>Results</i>. The evaluation of literature quality showed that the included studies had excellent methodological quality. A meta-analysis revealed that different sources of MSCs improved knee function and pain more effectively among patients suffering from knee OA (KOA) than controls. The results of the network meta-analysis showed the following: short-term functional improvement (the indexes were evaluated after 6 months of follow-up) (WOMAC total score: bone marrow-derived MSC (BMMSC) vs. adipose-derived MSC (ADMSC) (mean difference (MD) = −20.12, 95% confidence interval (CI) −125.24 to 42.88), umbilical cord-derived MSC (UCMSC) (MD = −7.81, 95% CI −158.13 to 74.99); WOMAC stiffness: BMMSC vs. ADMSC (MD = −0.51, 95% CI −7.27 to 4.29), UCMSC (MD = −0.75, 95% CI −9.74 to 6.63); WOMAC functional limitation: BMMSC vs. ADMSC (MD = −12.22, 95% CI −35.05 to 18.86), UCMSC (MD = −9.31, 95% CI −44.26 to 35.27)). Long-term functional improvement (the indexes were evaluated after 12 months of follow-up) (WOMAC total: BMMSC vs. ADMSC (MD = −176.77, 95% CI −757.1 to 378.25), UCMSC (MD = −181.55, 95% CI −937.83 to 541.13); WOMAC stiffness: BMMSC vs. ADMSC (MD = −0.5, 95% CI −26.05 to 18.61), UCMSC (MD = −1.03, 95% CI −30.44 to 21.69); WOMAC functional limitation: BMMSC vs. ADMSC (MD = −5.18, 95% CI −316.72 to 177.1), UCMSC (MD = −8.33, 95% CI −358.78 to 218.76)). Short-term pain relief (the indexes were evaluated after 6 months of follow-up) (VAS score: UCMSC vs. BMMSC (MD = −10.92, 95% CI −31.79 to 12.03), ADMSC (MD = −14.02, 95% CI −36.01 to 9.81), PLMSC (MD = −17.09, 95% CI −46.31 to 13.17); WOMAC pain relief: BMMSC vs. ADMSC (MD = −11.42, 95% CI −39.52 to 11.77), UCMSC (MD = −6.73, 95% CI −47.36 to 29.15)). Long-term pain relief (the indexes were evaluated after 12 months of follow-up) (VAS score: BMMSC vs. UCMSC (MD = −4.33, 95% CI −36.81 to 27.08)","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"24 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141190111","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}
Chronic nonhealing wounds significantly reduce patients’ quality of life and are a major burden on healthcare systems. Over the past few decades, tissue engineering materials have emerged as a viable option for wound healing, with cell-derived extracellular matrix (CDM) showing remarkable results. The CDM’s compatibility and resemblance to the natural tissue microenvironment confer distinct advantages to tissue-engineered scaffolds in wound repair. This review summarizes the current processes for CDM preparation, various cell decellularization protocols, and common characterization methods. Furthermore, it discusses the applications of CDM in wound healing, including skin defect and wound repair, angiogenesis, and engineered vessels, and offers perspectives on future developments.
{"title":"Cell-Derived Matrix: Production, Decellularization, and Application of Wound Repair","authors":"Yidan Xu, Yao Yao, Jianhua Gao","doi":"10.1155/2024/7398473","DOIUrl":"https://doi.org/10.1155/2024/7398473","url":null,"abstract":"Chronic nonhealing wounds significantly reduce patients’ quality of life and are a major burden on healthcare systems. Over the past few decades, tissue engineering materials have emerged as a viable option for wound healing, with cell-derived extracellular matrix (CDM) showing remarkable results. The CDM’s compatibility and resemblance to the natural tissue microenvironment confer distinct advantages to tissue-engineered scaffolds in wound repair. This review summarizes the current processes for CDM preparation, various cell decellularization protocols, and common characterization methods. Furthermore, it discusses the applications of CDM in wound healing, including skin defect and wound repair, angiogenesis, and engineered vessels, and offers perspectives on future developments.","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"45 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141190226","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}
Weili Han, Guofang Lu, Sheng Zhao, Rui Wang, Haohao Zhang, Kun Liu, Yongzhan Nie, Jiaqiang Dong
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.
{"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}
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 in vivo. 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.
{"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}
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 (). 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.
{"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}
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.
{"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}
Background. 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. Materials and Methods. 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. Results. 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. Conclusions. 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.
{"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}
Yong-xin Mai, Zhi-peng Li, Feng-xiang Pang, Shu-ting Zhou, Nan Li, Yu-yan Wang, Jin-fang Zhang
Objectives. Traditional Chinese medicine Cortex Eucommiae has been used to treat bone fracture for hundreds of years, which exerts a significant improvement in fracture healing. Aucubin, a derivative isolated from Cortex Eucommiae, 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. Materials and Methods. 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/β-catenin signaling were detected by qPCR examination, western blotting, and luciferase activity assays. Using the femur fracture mice model, the in vivo effect of Aucubin on bone formation was monitored by X-ray, micro-CT, histomorphometry, and immunohistochemistry staining. Results. In the present study, Aucubin was found to significantly promote osteogenic differentiation in vitro and stimulated bone formation in vivo. Regarding to the underlying mechanism, H19 was found to be obviously upregulated by Aucubin in MSCs and thus induced the activation of Wnt/β-catenin signaling. Moreover, H19 knockdown partially reversed the Aucubin-induced osteogenic differentiation and successfully suppressed the activation of Wnt/β-catenin signaling. We therefore suggested that Aucubin induced the activation of Wnt/β-catenin signaling through promoting H19 expression. Conclusion. Our results demonstrated that Aucubin promoted osteogenesis in vitro and facilitated fracture healing in vivo through the H19-Wnt/β-catenin regulatory axis.
{"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}
Panpan Lu, Guangchun Dai, Liu Shi, Yingjuan Li, Ming Zhang, Hao Wang, Yunfeng Rui
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/β-catenin signaling was activated in TSPCs under high glucose, and HMGB1 knockdown inhibited the activity of RAGE/β-catenin signaling. Inhibition of RAGE/β-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/β-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.
{"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}
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.
{"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}
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