首页 > 最新文献

World journal of stem cells最新文献

英文 中文
Gut microbiota modulating intestinal stem cell differentiation. 肠道微生物群调节肠道干细胞分化
IF 3.6 3区 医学 Q3 CELL & TISSUE ENGINEERING Pub Date : 2024-06-26 DOI: 10.4252/wjsc.v16.i6.619
Lin He, Chen Zhu, Xiang-Feng Zhou, Shu-E Zeng, Le Zhang, Kuan Li

Proliferation and differentiation of intestinal stem cell (ISC) to replace damaged gut mucosal epithelial cells in inflammatory states is a critical step in ameliorating gut inflammation. However, when this disordered proliferation continues, it induces the ISC to enter a cancerous state. The gut microbiota on the free surface of the gut mucosal barrier is able to interact with ISC on a sustained basis. Microbiota metabolites are able to regulate the proliferation of gut stem and progenitor cells through transcription factors, while in steady state, differentiated colonocytes are able to break down such metabolites, thereby protecting stem cells at the gut crypt. In the future, the gut flora and its metabolites mediating the regulation of ISC differentiation will be a potential treatment for enteropathies.

肠道干细胞(ISC)的增殖和分化取代炎症状态下受损的肠道粘膜上皮细胞,是改善肠道炎症的关键步骤。然而,当这种无序增殖持续下去时,就会诱导肠干细胞进入癌变状态。肠道粘膜屏障游离面上的肠道微生物群能够与 ISC 持续互动。微生物群代谢产物能够通过转录因子调节肠道干细胞和祖细胞的增殖,而在稳定状态下,分化的结肠细胞能够分解这些代谢产物,从而保护肠道隐窝处的干细胞。未来,肠道菌群及其代谢产物介导的肠道干细胞分化调节将成为治疗肠道疾病的潜在方法。
{"title":"Gut microbiota modulating intestinal stem cell differentiation.","authors":"Lin He, Chen Zhu, Xiang-Feng Zhou, Shu-E Zeng, Le Zhang, Kuan Li","doi":"10.4252/wjsc.v16.i6.619","DOIUrl":"10.4252/wjsc.v16.i6.619","url":null,"abstract":"<p><p>Proliferation and differentiation of intestinal stem cell (ISC) to replace damaged gut mucosal epithelial cells in inflammatory states is a critical step in ameliorating gut inflammation. However, when this disordered proliferation continues, it induces the ISC to enter a cancerous state. The gut microbiota on the free surface of the gut mucosal barrier is able to interact with ISC on a sustained basis. Microbiota metabolites are able to regulate the proliferation of gut stem and progenitor cells through transcription factors, while in steady state, differentiated colonocytes are able to break down such metabolites, thereby protecting stem cells at the gut crypt. In the future, the gut flora and its metabolites mediating the regulation of ISC differentiation will be a potential treatment for enteropathies.</p>","PeriodicalId":23775,"journal":{"name":"World journal of stem cells","volume":"16 6","pages":"619-622"},"PeriodicalIF":3.6,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11212547/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141474722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Safety and efficiency of Wharton's Jelly-derived mesenchymal stem cell administration in patients with traumatic brain injury: First results of a phase I study. 脑外伤患者服用沃顿果冻间充质干细胞的安全性和有效性:一期研究的初步结果。
IF 3.6 3区 医学 Q3 CELL & TISSUE ENGINEERING Pub Date : 2024-06-26 DOI: 10.4252/wjsc.v16.i6.641
Serdar Kabatas, Erdinç Civelek, Osman Boyalı, Gülseli Berivan Sezen, Omer Ozdemir, Yeliz Bahar-Ozdemir, Necati Kaplan, Eyüp Can Savrunlu, Erdal Karaöz

Background: Traumatic brain injury (TBI) is characterized by a disruption in the normal function of the brain due to an injury following a trauma, which can potentially cause severe physical, cognitive, and emotional impairment. Stem cell transplantation has evolved as a novel treatment modality in the management of TBI, as it has the potential to arrest the degeneration and promote regeneration of new cells in the brain. Wharton's Jelly-derived mesenchymal stem cells (WJ-MSCs) have recently shown beneficial effects in the functional recovery of neurological deficits.

Aim: To evaluate the safety and efficiency of MSC therapy in TBI.

Methods: We present 6 patients, 4 male and 2 female aged between 21 and 27 years who suffered a TBI. These 6 patients underwent 6 doses of intrathecal, intramuscular (i.m.) and intravenous transplantation of WJ-MSCs at a target dose of 1 × 106/kg for each application route. Spasticity was assessed using the Modified Ashworth scale (MAS), motor function according to the Medical Research Council Muscle Strength Scale, quality of life was assessed by the Functional Independence Measure (FIM) scale and Karnofsky Performance Status scale.

Results: Our patients showed only early, transient complications, such as subfebrile fever, mild headache, and muscle pain due to i.m. injection, which resolved within 24 h. During the one year follow-up, no other safety issues or adverse events were reported. These 6 patients showed improvements in their cognitive abilities, muscle spasticity, muscle strength, performance scores and fine motor skills when compared before and after the intervention. MAS values, which we used to assess spasticity, were observed to statistically significantly decrease for both left and right sides (P < 0.001). The FIM scale includes both motor scores (P < 0.05) and cognitive scores (P < 0.001) and showed a significant increase in pretest posttest analyses. The difference observed in the participants' Karnofsky Performance Scale values pre and post the intervention was statistically significant (P < 0.001).

Conclusion: This study showed that cell transplantation has a safe, effective and promising future in the management of TBI.

背景:创伤性脑损伤(TBI)的特点是,由于创伤后的损伤,大脑的正常功能受到破坏,有可能导致严重的身体、认知和情感损伤。干细胞移植已发展成为治疗创伤性脑损伤的一种新型治疗方式,因为它有可能阻止大脑中新细胞的退化并促进其再生。沃顿果冻间充质干细胞(WJ-MSCs)最近在神经功能缺损的功能恢复方面显示出有益的效果:研究对象为 6 名创伤性脑损伤患者,其中 4 男 2 女,年龄在 21 岁至 27 岁之间。这 6 名患者接受了 6 次 WJ 间充质干细胞鞘内移植、肌肉注射(i.m.)和静脉注射,每种应用途径的目标剂量均为 1 × 106/kg。用改良阿什沃斯量表(MAS)评估痉挛程度,用医学研究委员会肌力量表评估运动功能,用功能独立性量表(FIM)和卡诺夫斯基表现状态量表评估生活质量:在一年的随访中,没有出现其他安全问题或不良事件。与干预前后相比,这 6 名患者在认知能力、肌肉痉挛、肌肉力量、表现评分和精细运动技能方面均有所改善。我们用来评估痉挛程度的 MAS 值在统计上观察到左右两侧均显著下降(P < 0.001)。FIM 量表包括运动得分(P < 0.05)和认知得分(P < 0.001),在测试前和测试后的分析中均显示出显著的增长。干预前后观察到的参与者卡诺夫斯基表现量表值差异具有统计学意义(P < 0.001):这项研究表明,细胞移植在治疗创伤性脑损伤方面安全、有效且前景广阔。
{"title":"Safety and efficiency of Wharton's Jelly-derived mesenchymal stem cell administration in patients with traumatic brain injury: First results of a phase I study.","authors":"Serdar Kabatas, Erdinç Civelek, Osman Boyalı, Gülseli Berivan Sezen, Omer Ozdemir, Yeliz Bahar-Ozdemir, Necati Kaplan, Eyüp Can Savrunlu, Erdal Karaöz","doi":"10.4252/wjsc.v16.i6.641","DOIUrl":"10.4252/wjsc.v16.i6.641","url":null,"abstract":"<p><strong>Background: </strong>Traumatic brain injury (TBI) is characterized by a disruption in the normal function of the brain due to an injury following a trauma, which can potentially cause severe physical, cognitive, and emotional impairment. Stem cell transplantation has evolved as a novel treatment modality in the management of TBI, as it has the potential to arrest the degeneration and promote regeneration of new cells in the brain. Wharton's Jelly-derived mesenchymal stem cells (WJ-MSCs) have recently shown beneficial effects in the functional recovery of neurological deficits.</p><p><strong>Aim: </strong>To evaluate the safety and efficiency of MSC therapy in TBI.</p><p><strong>Methods: </strong>We present 6 patients, 4 male and 2 female aged between 21 and 27 years who suffered a TBI. These 6 patients underwent 6 doses of intrathecal, intramuscular (i.m.) and intravenous transplantation of WJ-MSCs at a target dose of 1 × 10<sup>6</sup>/kg for each application route. Spasticity was assessed using the Modified Ashworth scale (MAS), motor function according to the Medical Research Council Muscle Strength Scale, quality of life was assessed by the Functional Independence Measure (FIM) scale and Karnofsky Performance Status scale.</p><p><strong>Results: </strong>Our patients showed only early, transient complications, such as subfebrile fever, mild headache, and muscle pain due to i.m. injection, which resolved within 24 h. During the one year follow-up, no other safety issues or adverse events were reported. These 6 patients showed improvements in their cognitive abilities, muscle spasticity, muscle strength, performance scores and fine motor skills when compared before and after the intervention. MAS values, which we used to assess spasticity, were observed to statistically significantly decrease for both left and right sides (<i>P</i> < 0.001). The FIM scale includes both motor scores (<i>P</i> < 0.05) and cognitive scores (<i>P</i> < 0.001) and showed a significant increase in pretest posttest analyses. The difference observed in the participants' Karnofsky Performance Scale values pre and post the intervention was statistically significant (<i>P</i> < 0.001).</p><p><strong>Conclusion: </strong>This study showed that cell transplantation has a safe, effective and promising future in the management of TBI.</p>","PeriodicalId":23775,"journal":{"name":"World journal of stem cells","volume":"16 6","pages":"641-655"},"PeriodicalIF":3.6,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11212551/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141471039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Exosomes from umbilical cord mesenchymal stromal cells promote the collagen production of fibroblasts from pelvic organ prolapse. 来自脐带间充质基质细胞的外泌体可促进盆腔器官脱垂成纤维细胞产生胶原蛋白。
IF 3.6 3区 医学 Q3 CELL & TISSUE ENGINEERING Pub Date : 2024-06-26 DOI: 10.4252/wjsc.v16.i6.708
Lei-Mei Xu, Xin-Xin Yu, Ning Zhang, Yi-Song Chen

Background: Pelvic organ prolapse (POP) involves pelvic organ herniation into the vagina due to pelvic floor tissue laxity, and vaginal structure is an essential factor. In POP, the vaginal walls exhibit abnormal collagen distribution and decreased fibroblast levels and functions. The intricate etiology of POP and the prohibition of transvaginal meshes in pelvic reconstruction surgery present challenges in targeted therapy development. Human umbilical cord mesenchymal stromal cells (hucMSCs) present limitations, but their exosomes (hucMSC-Exo) are promising therapeutic tools for promoting fibroblast proliferation and extracellular matrix remodeling.

Aim: To investigate the effects of hucMSC-Exo on the functions of primary vaginal fibroblasts and to elucidate the underlying mechanism involved.

Methods: Human vaginal wall collagen content was assessed by Masson's trichrome and Sirius blue staining. Gene expression differences in fibroblasts from patients with and without POP were assessed via RNA sequencing (RNA-seq). The effects of hucMSC-Exo on fibroblasts were determined via functional experiments in vitro. RNA-seq data from fibroblasts exposed to hucMSC-Exo and microRNA (miRNA) sequencing data from hucMSC-Exo were jointly analyzed to identify effective molecules.

Results: In POP, the vaginal wall exhibited abnormal collagen distribution and reduced fibroblast 1 quality and quantity. Treatment with 4 or 6 μg/mL hucMSC-Exo suppressed inflammation in POP group fibroblasts, stimulated primary fibroblast growth, and elevated collagen I (Col1) production in vitro. High-throughput RNA-seq of fibroblasts treated with hucMSC-Exo and miRNA sequencing of hucMSC-Exo revealed that abundant exosomal miRNAs downregulated matrix metalloproteinase 11 (MMP11) expression.

Conclusion: HucMSC-Exo normalized the growth and function of primary fibroblasts from patients with POP by promoting cell growth and Col1 expression in vitro. Abundant miRNAs in hucMSC-Exo targeted and downregulated MMP11 expression. HucMSC-Exo-based therapy may be ideal for safely and effectively treating POP.

背景:盆腔脏器脱垂(POP)是指由于盆底组织松弛导致盆腔脏器疝入阴道,而阴道结构是一个重要因素。POP 患者的阴道壁胶原蛋白分布异常,成纤维细胞水平和功能下降。POP 的病因错综复杂,而且盆腔重建手术中禁止使用经阴道网,这给靶向疗法的开发带来了挑战。人脐带间充质基质细胞(hucMSCs)存在局限性,但其外泌体(hucMSC-Exo)是促进成纤维细胞增殖和细胞外基质重塑的有前途的治疗工具。通过 RNA 测序(RNA-seq)评估了 POP 患者和非 POP 患者成纤维细胞的基因表达差异。通过体外功能实验确定了 hucMSC-Exo 对成纤维细胞的影响。对暴露于 hucMSC-Exo 的成纤维细胞的 RNA-seq 数据和 hucMSC-Exo 的 microRNA (miRNA) 测序数据进行了联合分析,以确定有效分子:结果:POP 患者的阴道壁胶原分布异常,成纤维细胞 1 的质量和数量下降。用 4 或 6 μg/mL hucMSC-Exo 治疗可抑制 POP 组成纤维细胞的炎症反应,刺激原发性成纤维细胞生长,并提高体外胶原蛋白 I(Col1)的生成。用hucMSC-Exo处理成纤维细胞的高通量RNA-seq和hucMSC-Exo的miRNA测序显示,丰富的外泌体miRNA下调了基质金属蛋白酶11(MMP11)的表达:结论:HucMSC-Exo通过促进细胞生长和体外Col1的表达,使POP患者原代成纤维细胞的生长和功能正常化。hucMSC-Exo中丰富的miRNAs靶向并下调了MMP11的表达。基于 HucMSC-Exo 的疗法可能是安全有效治疗 POP 的理想方法。
{"title":"Exosomes from umbilical cord mesenchymal stromal cells promote the collagen production of fibroblasts from pelvic organ prolapse.","authors":"Lei-Mei Xu, Xin-Xin Yu, Ning Zhang, Yi-Song Chen","doi":"10.4252/wjsc.v16.i6.708","DOIUrl":"10.4252/wjsc.v16.i6.708","url":null,"abstract":"<p><strong>Background: </strong>Pelvic organ prolapse (POP) involves pelvic organ herniation into the vagina due to pelvic floor tissue laxity, and vaginal structure is an essential factor. In POP, the vaginal walls exhibit abnormal collagen distribution and decreased fibroblast levels and functions. The intricate etiology of POP and the prohibition of transvaginal meshes in pelvic reconstruction surgery present challenges in targeted therapy development. Human umbilical cord mesenchymal stromal cells (hucMSCs) present limitations, but their exosomes (hucMSC-Exo) are promising therapeutic tools for promoting fibroblast proliferation and extracellular matrix remodeling.</p><p><strong>Aim: </strong>To investigate the effects of hucMSC-Exo on the functions of primary vaginal fibroblasts and to elucidate the underlying mechanism involved.</p><p><strong>Methods: </strong>Human vaginal wall collagen content was assessed by Masson's trichrome and Sirius blue staining. Gene expression differences in fibroblasts from patients with and without POP were assessed <i>via</i> RNA sequencing (RNA-seq). The effects of hucMSC-Exo on fibroblasts were determined <i>via</i> functional experiments <i>in vitro</i>. RNA-seq data from fibroblasts exposed to hucMSC-Exo and microRNA (miRNA) sequencing data from hucMSC-Exo were jointly analyzed to identify effective molecules.</p><p><strong>Results: </strong>In POP, the vaginal wall exhibited abnormal collagen distribution and reduced fibroblast 1 quality and quantity. Treatment with 4 or 6 μg/mL hucMSC-Exo suppressed inflammation in POP group fibroblasts, stimulated primary fibroblast growth, and elevated collagen I (Col1) production <i>in vitro</i>. High-throughput RNA-seq of fibroblasts treated with hucMSC-Exo and miRNA sequencing of hucMSC-Exo revealed that abundant exosomal miRNAs downregulated matrix metalloproteinase 11 (MMP11) expression.</p><p><strong>Conclusion: </strong>HucMSC-Exo normalized the growth and function of primary fibroblasts from patients with POP by promoting cell growth and Col1 expression <i>in vitro</i>. Abundant miRNAs in hucMSC-Exo targeted and downregulated MMP11 expression. HucMSC-Exo-based therapy may be ideal for safely and effectively treating POP.</p>","PeriodicalId":23775,"journal":{"name":"World journal of stem cells","volume":"16 6","pages":"708-727"},"PeriodicalIF":3.6,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11212552/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141471111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Searching for the optimal precondition procedure for mesenchymal stem/stromal cell treatment: Facts and perspectives. 寻找间充质干细胞/基质细胞治疗的最佳前提条件程序:事实与展望。
IF 3.6 3区 医学 Q3 CELL & TISSUE ENGINEERING Pub Date : 2024-06-26 DOI: 10.4252/wjsc.v16.i6.615
Yu-Dong Zhao, Yong-Can Huang, Wei-Shi Li

Mesenchymal stem/stromal cells are potential optimal cell sources for stem cell therapies, and pretreatment has proven to enhance cell vitality and function. In a recent publication, Li et al explored a new combination of pretreatment conditions. Here, we present an editorial to comment on their work and provide our view on mesenchymal stem/stromal cell precondition.

间充质干细胞/基质细胞是干细胞疗法潜在的最佳细胞来源,预处理已被证明能增强细胞活力和功能。在最近发表的一篇文章中,Li 等人探索了一种新的预处理条件组合。在此,我们将发表一篇社论,对他们的工作进行评论,并提出我们对间充质干细胞/基质细胞预处理条件的看法。
{"title":"Searching for the optimal precondition procedure for mesenchymal stem/stromal cell treatment: Facts and perspectives.","authors":"Yu-Dong Zhao, Yong-Can Huang, Wei-Shi Li","doi":"10.4252/wjsc.v16.i6.615","DOIUrl":"10.4252/wjsc.v16.i6.615","url":null,"abstract":"<p><p>Mesenchymal stem/stromal cells are potential optimal cell sources for stem cell therapies, and pretreatment has proven to enhance cell vitality and function. In a recent publication, Li <i>et al</i> explored a new combination of pretreatment conditions. Here, we present an editorial to comment on their work and provide our view on mesenchymal stem/stromal cell precondition.</p>","PeriodicalId":23775,"journal":{"name":"World journal of stem cells","volume":"16 6","pages":"615-618"},"PeriodicalIF":3.6,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11212554/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141471040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Umbilical cord mesenchymal stem cell exosomes alleviate necrotizing enterocolitis in neonatal mice by regulating intestinal epithelial cells autophagy. 脐带间充质干细胞外泌体通过调节肠上皮细胞自噬缓解新生小鼠的坏死性小肠结肠炎
IF 3.6 3区 医学 Q3 CELL & TISSUE ENGINEERING Pub Date : 2024-06-26 DOI: 10.4252/wjsc.v16.i6.728
Lin Zhu, Lu He, Wu Duan, Bo Yang, Ning Li

Background: Necrotizing enterocolitis (NEC) is a severe gastrointestinal disease that affects premature infants. Although mounting evidence supports the therapeutic effect of exosomes on NEC, the underlying mechanisms remain unclear.

Aim: To investigate the mechanisms underlying the regulation of inflammatory response and intestinal barrier function by umbilical cord mesenchymal stem cell (UCMSCs) exosomes, as well as their potential in alleviating NEC in neonatal mice.

Methods: NEC was induced in 5-d-old C57BL/6 pups through hypoxia and gavage feeding of formula containing lipopolysaccharide (LPS), after which the mice received human UCMSC exosomes (hUCMSC-exos). The control mice were allowed to breastfeed with their dams. Ileal tissues were collected from the mice and analyzed by histopathology and immunoblotting. Colon tissues were collected from NEC neonates and analyzed by immunofluorescence. Molecular biology and cell culture approaches were employed to study the related mechanisms in intestinal epithelial cells.

Results: We found that autophagy is overactivated in intestinal epithelial cells during NEC, resulting in reduced expression of tight junction proteins and an increased inflammatory response. The ability of hUCMSC-exos to ameliorate NEC in a mouse model was dependent on decreased intestinal autophagy. We also showed that hUCMSC-exos alleviate the inflammatory response and increase migration ability in intestinal epithelial cells induced by LPS.

Conclusion: These results contribute to a better understanding of the protective mechanisms of hUCMSC-exos against NEC and provide a new theoretical and experimental foundation for NEC treatment. These findings also enhance our understanding of the role of the autophagy mechanism in NEC, offering potential avenues for identifying new therapeutic targets.

背景:坏死性小肠结肠炎(NEC坏死性小肠结肠炎(NEC)是一种影响早产儿的严重胃肠道疾病。目的:研究脐带间充质干细胞(UCMSCs)外泌体调节炎症反应和肠屏障功能的机制,以及外泌体缓解新生小鼠坏死性小肠结肠炎的潜力:方法:通过缺氧和灌胃含有脂多糖(LPS)的配方奶诱导5天大的C57BL/6幼鼠发生NEC,然后让小鼠接受人UCMSC外泌体(hUCMSC-exos)。对照组小鼠与母鼠一起进行母乳喂养。收集小鼠的回肠组织并进行组织病理学和免疫印迹分析。收集 NEC 新生儿的结肠组织并进行免疫荧光分析。采用分子生物学和细胞培养方法研究肠上皮细胞的相关机制:结果:我们发现自噬在 NEC 期间在肠上皮细胞中被过度激活,导致紧密连接蛋白表达减少和炎症反应增加。hUCMSC-exos 在小鼠模型中改善 NEC 的能力取决于肠道自噬的减少。我们还发现,hUCMSC-exos 可减轻 LPS 诱导的肠上皮细胞炎症反应并提高其迁移能力:这些结果有助于更好地理解 hUCMSC-exos 对 NEC 的保护机制,并为 NEC 治疗提供了新的理论和实验基础。这些发现还加深了我们对自噬机制在 NEC 中作用的理解,为确定新的治疗靶点提供了潜在途径。
{"title":"Umbilical cord mesenchymal stem cell exosomes alleviate necrotizing enterocolitis in neonatal mice by regulating intestinal epithelial cells autophagy.","authors":"Lin Zhu, Lu He, Wu Duan, Bo Yang, Ning Li","doi":"10.4252/wjsc.v16.i6.728","DOIUrl":"10.4252/wjsc.v16.i6.728","url":null,"abstract":"<p><strong>Background: </strong>Necrotizing enterocolitis (NEC) is a severe gastrointestinal disease that affects premature infants. Although mounting evidence supports the therapeutic effect of exosomes on NEC, the underlying mechanisms remain unclear.</p><p><strong>Aim: </strong>To investigate the mechanisms underlying the regulation of inflammatory response and intestinal barrier function by umbilical cord mesenchymal stem cell (UCMSCs) exosomes, as well as their potential in alleviating NEC in neonatal mice.</p><p><strong>Methods: </strong>NEC was induced in 5-d-old C57BL/6 pups through hypoxia and gavage feeding of formula containing lipopolysaccharide (LPS), after which the mice received human UCMSC exosomes (hUCMSC-exos). The control mice were allowed to breastfeed with their dams. Ileal tissues were collected from the mice and analyzed by histopathology and immunoblotting. Colon tissues were collected from NEC neonates and analyzed by immunofluorescence. Molecular biology and cell culture approaches were employed to study the related mechanisms in intestinal epithelial cells.</p><p><strong>Results: </strong>We found that autophagy is overactivated in intestinal epithelial cells during NEC, resulting in reduced expression of tight junction proteins and an increased inflammatory response. The ability of hUCMSC-exos to ameliorate NEC in a mouse model was dependent on decreased intestinal autophagy. We also showed that hUCMSC-exos alleviate the inflammatory response and increase migration ability in intestinal epithelial cells induced by LPS.</p><p><strong>Conclusion: </strong>These results contribute to a better understanding of the protective mechanisms of hUCMSC-exos against NEC and provide a new theoretical and experimental foundation for NEC treatment. These findings also enhance our understanding of the role of the autophagy mechanism in NEC, offering potential avenues for identifying new therapeutic targets.</p>","PeriodicalId":23775,"journal":{"name":"World journal of stem cells","volume":"16 6","pages":"728-738"},"PeriodicalIF":3.6,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11212546/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141471041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Mesenchymal stem cells-extracellular vesicles alleviate pulmonary fibrosis by regulating immunomodulators. 间充质干细胞-细胞外囊泡通过调节免疫调节剂缓解肺纤维化。
IF 3.6 3区 医学 Q3 CELL & TISSUE ENGINEERING Pub Date : 2024-06-26 DOI: 10.4252/wjsc.v16.i6.670
Ying Gao, Mei-Fang Liu, Yang Li, Xi Liu, Yu-Jie Cao, Qian-Fa Long, Jun Yu, Jian-Ying Li

Background: Pulmonary fibrosis (PF) is a chronic interstitial lung disease characterized by fibroblast proliferation and extracellular matrix formation, causing structural damage and lung failure. Stem cell therapy and mesenchymal stem cells-extracellular vesicles (MSC-EVs) offer new hope for PF treatment.

Aim: To investigate the therapeutic potential of MSC-EVs in alleviating fibrosis, oxidative stress, and immune inflammation in A549 cells and bleomycin (BLM)-induced mouse model.

Methods: The effect of MSC-EVs on A549 cells was assessed by fibrosis markers [collagen I and α-smooth muscle actin (α-SMA), oxidative stress regulators [nuclear factor E2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1), and inflammatory regulators [nuclear factor-kappaB (NF-κB) p65, interleukin (IL)-1β, and IL-2]. Similarly, they were assessed in the lungs of mice where PF was induced by BLM after MSC-EV transfection. MSC-EVs ion PF mice were detected by pathological staining and western blot. Single-cell RNA sequencing was performed to investigate the effects of the MSC-EVs on gene expression profiles of macrophages after modeling in mice.

Results: Transforming growth factor (TGF)-β1 enhanced fibrosis in A549 cells, significantly increasing collagen I and α-SMA levels. Notably, treatment with MSC-EVs demonstrated a remarkable alleviation of these effects. Similarly, the expression of oxidative stress regulators, such as Nrf2 and HO-1, along with inflammatory regulators, including NF-κB p65 and IL-1β, were mitigated by MSC-EV treatment. Furthermore, in a parallel manner, MSC-EVs exhibited a downregulatory impact on collagen deposition, oxidative stress injuries, and inflammatory-related cytokines in the lungs of mice with PF. Additionally, the mRNA sequencing results suggested that BLM may induce PF in mice by upregulating pulmonary collagen fiber deposition and triggering an immune inflammatory response. The findings collectively highlight the potential therapeutic efficacy of MSC-EVs in ameliorating fibrotic processes, oxidative stress, and inflammatory responses associated with PF.

Conclusion: MSC-EVs could ameliorate fibrosis in vitro and in vivo by downregulating collagen deposition, oxidative stress, and immune-inflammatory responses.

背景:肺纤维化(PF)是一种慢性间质性肺病,以成纤维细胞增殖和细胞外基质形成为特征,导致结构损伤和肺功能衰竭。干细胞疗法和间充质干细胞胞外小泡(MSC-EVs)为肺纤维化治疗带来了新希望。目的:研究间充质干细胞胞外小泡在缓解A549细胞和博莱霉素(BLM)诱导的小鼠模型纤维化、氧化应激和免疫炎症方面的治疗潜力:方法:间充质干细胞-EV对A549细胞的影响通过纤维化标志物[胶原蛋白I和α-平滑肌肌动蛋白(α-SMA)]、氧化应激调节因子[核因子E2相关因子2(Nrf2)和血红素氧合酶-1(HO-1)]以及炎症调节因子[核因子-kappaB(NF-κB)p65、白细胞介素(IL)-1β和IL-2]进行评估。同样,它们也在间充质干细胞-EV转染后通过 BLM 诱导 PF 的小鼠肺部进行了评估。通过病理染色和免疫印迹检测MSC-EV离子PF小鼠。通过单细胞RNA测序研究了间充质干细胞-EV对小鼠建模后巨噬细胞基因表达谱的影响:结果:转化生长因子(TGF)-β1增强了A549细胞的纤维化,显著提高了胶原蛋白I和α-SMA的水平。值得注意的是,使用间充质干细胞-EVs 治疗可明显缓解这些影响。同样,间充质干细胞-脑白质(MSC-EV)处理也减轻了氧化应激调节因子(如 Nrf2 和 HO-1)以及炎症调节因子(包括 NF-κB p65 和 IL-1β)的表达。此外,间充质干细胞-脑白质(MSC-EV)还以平行的方式下调了PF小鼠肺部的胶原沉积、氧化应激损伤和炎症相关细胞因子。此外,mRNA 测序结果表明,BLM 可通过上调肺胶原纤维沉积和引发免疫炎症反应来诱导小鼠的 PF。这些发现共同凸显了间充质干细胞-EVs在改善与PF相关的纤维化过程、氧化应激和炎症反应方面的潜在疗效:结论:间充质干细胞-脑白质可通过下调胶原沉积、氧化应激和免疫炎症反应来改善体外和体内的纤维化。
{"title":"Mesenchymal stem cells-extracellular vesicles alleviate pulmonary fibrosis by regulating immunomodulators.","authors":"Ying Gao, Mei-Fang Liu, Yang Li, Xi Liu, Yu-Jie Cao, Qian-Fa Long, Jun Yu, Jian-Ying Li","doi":"10.4252/wjsc.v16.i6.670","DOIUrl":"10.4252/wjsc.v16.i6.670","url":null,"abstract":"<p><strong>Background: </strong>Pulmonary fibrosis (PF) is a chronic interstitial lung disease characterized by fibroblast proliferation and extracellular matrix formation, causing structural damage and lung failure. Stem cell therapy and mesenchymal stem cells-extracellular vesicles (MSC-EVs) offer new hope for PF treatment.</p><p><strong>Aim: </strong>To investigate the therapeutic potential of MSC-EVs in alleviating fibrosis, oxidative stress, and immune inflammation in A549 cells and bleomycin (BLM)-induced mouse model.</p><p><strong>Methods: </strong>The effect of MSC-EVs on A549 cells was assessed by fibrosis markers [collagen I and α-smooth muscle actin (α-SMA), oxidative stress regulators [nuclear factor E2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1), and inflammatory regulators [nuclear factor-kappaB (NF-κB) p65, interleukin (IL)-1β, and IL-2]. Similarly, they were assessed in the lungs of mice where PF was induced by BLM after MSC-EV transfection. MSC-EVs ion PF mice were detected by pathological staining and western blot. Single-cell RNA sequencing was performed to investigate the effects of the MSC-EVs on gene expression profiles of macrophages after modeling in mice.</p><p><strong>Results: </strong>Transforming growth factor (TGF)-β1 enhanced fibrosis in A549 cells, significantly increasing collagen I and α-SMA levels. Notably, treatment with MSC-EVs demonstrated a remarkable alleviation of these effects. Similarly, the expression of oxidative stress regulators, such as Nrf2 and HO-1, along with inflammatory regulators, including NF-κB p65 and IL-1β, were mitigated by MSC-EV treatment. Furthermore, in a parallel manner, MSC-EVs exhibited a downregulatory impact on collagen deposition, oxidative stress injuries, and inflammatory-related cytokines in the lungs of mice with PF. Additionally, the mRNA sequencing results suggested that BLM may induce PF in mice by upregulating pulmonary collagen fiber deposition and triggering an immune inflammatory response. The findings collectively highlight the potential therapeutic efficacy of MSC-EVs in ameliorating fibrotic processes, oxidative stress, and inflammatory responses associated with PF.</p><p><strong>Conclusion: </strong>MSC-EVs could ameliorate fibrosis <i>in vitro</i> and <i>in vivo</i> by downregulating collagen deposition, oxidative stress, and immune-inflammatory responses.</p>","PeriodicalId":23775,"journal":{"name":"World journal of stem cells","volume":"16 6","pages":"670-689"},"PeriodicalIF":3.6,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11212550/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141471112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Outcomes of combined mitochondria and mesenchymal stem cells-derived exosome therapy in rat acute respiratory distress syndrome and sepsis. 线粒体和间充质干细胞衍生外泌体联合疗法对大鼠急性呼吸窘迫综合征和败血症的疗效。
IF 3.6 3区 医学 Q3 CELL & TISSUE ENGINEERING Pub Date : 2024-06-26 DOI: 10.4252/wjsc.v16.i6.690
Kun-Chen Lin, Wen-Feng Fang, Jui-Ning Yeh, John Y Chiang, Hsin-Ju Chiang, Pei-Lin Shao, Pei-Hsun Sung, Hon-Kan Yip
<p><strong>Background: </strong>The treatment of acute respiratory distress syndrome (ARDS) complicated by sepsis syndrome (SS) remains challenging.</p><p><strong>Aim: </strong>To investigate whether combined adipose-derived mesenchymal-stem-cells (ADMSCs)-derived exosome (EX<sup>AD</sup>) and exogenous mitochondria (mito<sup>Ex</sup>) protect the lung from ARDS complicated by SS.</p><p><strong>Methods: </strong><i>In vitro</i> study, including L2 cells treated with lipopolysaccharide (LPS) and <i>in vivo</i> study including male-adult-SD rats categorized into groups 1 (sham-operated-control), 2 (ARDS-SS), 3 (ARDS-SS + EX<sup>AD</sup>), 4 (ARDS-SS + mito<sup>Ex</sup>), and 5 (ARDS-SS + EX<sup>AD</sup> + mito<sup>Ex</sup>), were included in the present study.</p><p><strong>Results: </strong><i>In vitro</i> study showed an abundance of mito<sup>Ex</sup> found in recipient-L2 cells, resulting in significantly higher mitochondrial-cytochrome-C, adenosine triphosphate and relative mitochondrial DNA levels (<i>P</i> < 0.001). The protein levels of inflammation [interleukin (IL)-1β/tumor necrosis factor (TNF)-α/nuclear factor-κB/toll-like receptor (TLR)-4/matrix-metalloproteinase (MMP)-9/oxidative-stress (NOX-1/NOX-2)/apoptosis (cleaved-caspase3/cleaved-poly (ADP-ribose) polymerase)] were significantly attenuated in lipopolysaccharide (LPS)-treated L2 cells with EX<sup>AD</sup> treatment than without EX<sup>AD</sup> treatment, whereas the protein expressions of cellular junctions [occluding/β-catenin/zonula occludens (ZO)-1/E-cadherin] exhibited an opposite pattern of inflammation (all <i>P</i> < 0.001). Animals were euthanized by 72 h post-48 h-ARDS induction, and lung tissues were harvested. By 72 h, flow cytometric analysis of bronchoalveolar lavage fluid demonstrated that the levels of inflammatory cells (Ly6G+/CD14+/CD68+/CD11<sup>b/c</sup>+/myeloperoxidase+) and albumin were lowest in group 1, highest in group 2, and significantly higher in groups 3 and 4 than in group 5 (all <i>P</i> < 0.0001), whereas arterial oxygen-saturation (SaO<sub>2</sub>%) displayed an opposite pattern of albumin among the groups. Histopathological findings of lung injury/fibrosis area and inflammatory/DNA-damaged markers (CD68+/γ-H2AX) displayed an identical pattern of SaO<sub>2</sub>% among the groups (all <i>P</i> < 0.0001). The protein expressions of inflammatory (TLR-4/MMP-9/IL-1β/TNF-α)/oxidative stress (NOX-1/NOX-2/p22phox/oxidized protein)/mitochondrial-damaged (cytosolic-cytochrome-C/dynamin-related protein 1)/autophagic (beclin-1/Atg-5/ratio of LC3B-II/LC3B-I) biomarkers exhibited a similar manner, whereas antioxidants [nuclear respiratory factor (Nrf)-1/Nrf-2]/cellular junctions (ZO-1/E-cadherin)/mitochondrial electron transport chain (complex I-V) exhibited an opposite manner of albumin among the groups (all <i>P</i> < 0.0001).</p><p><strong>Conclusion: </strong>Combined EX<sup>AD</sup>-mito<sup>Ex</sup> therapy was better than merely one for protecting the lu
背景:目的:研究脂肪间充质干细胞(ADMSCs)衍生的外泌体(EXAD)和外源性线粒体(mitoEx)是否能保护肺部免受脓毒症综合征(SS)并发急性呼吸窘迫综合征(ARDS)的影响:方法:体外研究包括经脂多糖(LPS)处理的L2细胞,体内研究包括雄性成年SD大鼠,分为1组(假手术对照组)、2组(ARDS-SS组)、3组(ARDS-SS + EXAD组)、4组(ARDS-SS + mitoEx组)和5组(ARDS-SS + EXAD + mitoEx组):体外研究显示,受体-L2细胞中发现了大量mitoEx,导致线粒体-细胞色素-C、三磷酸腺苷和线粒体DNA相对水平显著升高(P < 0.001)。炎症蛋白水平[白细胞介素(IL)-1β/肿瘤坏死因子(TNF)-α/核因子-κB/类花粉受体(TLR)-4/基质金属蛋白酶(MMP)-9/氧化应激(NOX-1/NOX-2)/细胞凋亡(cleaved-caspase3/cleaved-poly (ADP-ribose) polymerase)]在经EXAD处理的脂多糖(LPS)处理的L2细胞中比未经EXAD处理的细胞明显减少、而细胞连接蛋白[闭锁素/β-catenin/偶氮闭锁素(ZO)-1/E-cadherin]的表达则表现出与炎症相反的模式(均 P < 0.001).动物在 48 小时-ARDS 诱导后 72 小时安乐死,并收获肺组织。72 小时后,支气管肺泡灌洗液的流式细胞术分析表明,炎症细胞(Ly6G+/CD14+/CD68+/CD11b/c+/髓过氧化物酶+)和白蛋白的水平在第 1 组最低,在第 2 组最高,第 3 组和第 4 组明显高于第 5 组(均 P < 0.0001),而动脉血氧饱和度(SaO2%)在各组之间显示出与白蛋白相反的模式。肺损伤/纤维化面积和炎症/DNA损伤标志物(CD68+/γ-H2AX)的组织病理学结果显示,各组之间的SaO2%变化规律相同(均为P<0.0001)。炎症(TLR-4/MMP-9/IL-1β/TNF-α)/氧化应激(NOX-1/NOX-2/p22phox/氧化蛋白)/半软骨损伤(细胞质-细胞色素-C/Dynamin 相关蛋白 1)/自噬(beclin-1/Atg-5/LC3B-II/LC3B-I 的比率)生物标志物的蛋白质表达表现出相似的方式、而抗氧化剂[核呼吸因子(Nrf)-1/Nrf-2]/细胞连接(ZO-1/E-cadherin)/半胱氨酸电子传递链(复合物I-V)在各组中的表现与白蛋白的表现相反(均P < 0.0001):结论:EXAD-mitoEx联合疗法在保护肺部免受ARDS-SS诱导的损伤方面优于单一疗法。
{"title":"Outcomes of combined mitochondria and mesenchymal stem cells-derived exosome therapy in rat acute respiratory distress syndrome and sepsis.","authors":"Kun-Chen Lin, Wen-Feng Fang, Jui-Ning Yeh, John Y Chiang, Hsin-Ju Chiang, Pei-Lin Shao, Pei-Hsun Sung, Hon-Kan Yip","doi":"10.4252/wjsc.v16.i6.690","DOIUrl":"10.4252/wjsc.v16.i6.690","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;The treatment of acute respiratory distress syndrome (ARDS) complicated by sepsis syndrome (SS) remains challenging.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Aim: &lt;/strong&gt;To investigate whether combined adipose-derived mesenchymal-stem-cells (ADMSCs)-derived exosome (EX&lt;sup&gt;AD&lt;/sup&gt;) and exogenous mitochondria (mito&lt;sup&gt;Ex&lt;/sup&gt;) protect the lung from ARDS complicated by SS.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;&lt;i&gt;In vitro&lt;/i&gt; study, including L2 cells treated with lipopolysaccharide (LPS) and &lt;i&gt;in vivo&lt;/i&gt; study including male-adult-SD rats categorized into groups 1 (sham-operated-control), 2 (ARDS-SS), 3 (ARDS-SS + EX&lt;sup&gt;AD&lt;/sup&gt;), 4 (ARDS-SS + mito&lt;sup&gt;Ex&lt;/sup&gt;), and 5 (ARDS-SS + EX&lt;sup&gt;AD&lt;/sup&gt; + mito&lt;sup&gt;Ex&lt;/sup&gt;), were included in the present study.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;&lt;i&gt;In vitro&lt;/i&gt; study showed an abundance of mito&lt;sup&gt;Ex&lt;/sup&gt; found in recipient-L2 cells, resulting in significantly higher mitochondrial-cytochrome-C, adenosine triphosphate and relative mitochondrial DNA levels (&lt;i&gt;P&lt;/i&gt; &lt; 0.001). The protein levels of inflammation [interleukin (IL)-1β/tumor necrosis factor (TNF)-α/nuclear factor-κB/toll-like receptor (TLR)-4/matrix-metalloproteinase (MMP)-9/oxidative-stress (NOX-1/NOX-2)/apoptosis (cleaved-caspase3/cleaved-poly (ADP-ribose) polymerase)] were significantly attenuated in lipopolysaccharide (LPS)-treated L2 cells with EX&lt;sup&gt;AD&lt;/sup&gt; treatment than without EX&lt;sup&gt;AD&lt;/sup&gt; treatment, whereas the protein expressions of cellular junctions [occluding/β-catenin/zonula occludens (ZO)-1/E-cadherin] exhibited an opposite pattern of inflammation (all &lt;i&gt;P&lt;/i&gt; &lt; 0.001). Animals were euthanized by 72 h post-48 h-ARDS induction, and lung tissues were harvested. By 72 h, flow cytometric analysis of bronchoalveolar lavage fluid demonstrated that the levels of inflammatory cells (Ly6G+/CD14+/CD68+/CD11&lt;sup&gt;b/c&lt;/sup&gt;+/myeloperoxidase+) and albumin were lowest in group 1, highest in group 2, and significantly higher in groups 3 and 4 than in group 5 (all &lt;i&gt;P&lt;/i&gt; &lt; 0.0001), whereas arterial oxygen-saturation (SaO&lt;sub&gt;2&lt;/sub&gt;%) displayed an opposite pattern of albumin among the groups. Histopathological findings of lung injury/fibrosis area and inflammatory/DNA-damaged markers (CD68+/γ-H2AX) displayed an identical pattern of SaO&lt;sub&gt;2&lt;/sub&gt;% among the groups (all &lt;i&gt;P&lt;/i&gt; &lt; 0.0001). The protein expressions of inflammatory (TLR-4/MMP-9/IL-1β/TNF-α)/oxidative stress (NOX-1/NOX-2/p22phox/oxidized protein)/mitochondrial-damaged (cytosolic-cytochrome-C/dynamin-related protein 1)/autophagic (beclin-1/Atg-5/ratio of LC3B-II/LC3B-I) biomarkers exhibited a similar manner, whereas antioxidants [nuclear respiratory factor (Nrf)-1/Nrf-2]/cellular junctions (ZO-1/E-cadherin)/mitochondrial electron transport chain (complex I-V) exhibited an opposite manner of albumin among the groups (all &lt;i&gt;P&lt;/i&gt; &lt; 0.0001).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Combined EX&lt;sup&gt;AD&lt;/sup&gt;-mito&lt;sup&gt;Ex&lt;/sup&gt; therapy was better than merely one for protecting the lu","PeriodicalId":23775,"journal":{"name":"World journal of stem cells","volume":"16 6","pages":"690-707"},"PeriodicalIF":3.6,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11212548/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141471113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Priming mesenchymal stem cells to develop "super stem cells". 引导间充质干细胞发展 "超级干细胞"。
IF 3.6 3区 医学 Q3 CELL & TISSUE ENGINEERING Pub Date : 2024-06-26 DOI: 10.4252/wjsc.v16.i6.623
Khawaja Husnain Haider

The stem cell pre-treatment approaches at cellular and sub-cellular levels encompass physical manipulation of stem cells to growth factor treatment, genetic manipulation, and chemical and pharmacological treatment, each strategy having advantages and limitations. Most of these pre-treatment protocols are non-combinative. This editorial is a continuum of Li et al's published article and Wan et al's editorial focusing on the significance of pre-treatment strategies to enhance their stemness, immunoregulatory, and immunosuppressive properties. They have elaborated on the intricacies of the combinative pre-treatment protocol using pro-inflammatory cytokines and hypoxia. Applying a well-defined multi-pronged combinatorial strategy of mesenchymal stem cells (MSCs), pre-treatment based on the mechanistic understanding is expected to develop "Super MSCs", which will create a transformative shift in MSC-based therapies in clinical settings, potentially revolutionizing the field. Once optimized, the standardized protocols may be used with slight modifications to pre-treat different stem cells to develop "super stem cells" with augmented stemness, functionality, and reparability for diverse clinical applications with better outcomes.

细胞和亚细胞水平的干细胞预处理方法包括对干细胞进行物理操作、生长因子处理、基因操作以及化学和药物处理,每种策略都有其优势和局限性。这些预处理方案大多是非组合性的。这篇社论是Li等人发表的文章和Wan等人社论的延续,重点关注预处理策略对增强干细胞干性、免疫调节和免疫抑制特性的意义。他们详细阐述了使用促炎细胞因子和缺氧的联合预处理方案的复杂性。基于对机理的理解,应用间充质干细胞(MSCs)定义明确的多管齐下的组合策略进行预处理,有望开发出 "超级间充质干细胞",这将为基于间充质干细胞的临床疗法带来变革性的转变,有可能彻底改变这一领域。标准化方案一旦优化,可略加修改后用于不同干细胞的预处理,从而开发出具有增强干性、功能性和可修复性的 "超级干细胞",用于各种临床应用,取得更好的效果。
{"title":"Priming mesenchymal stem cells to develop \"super stem cells\".","authors":"Khawaja Husnain Haider","doi":"10.4252/wjsc.v16.i6.623","DOIUrl":"10.4252/wjsc.v16.i6.623","url":null,"abstract":"<p><p>The stem cell pre-treatment approaches at cellular and sub-cellular levels encompass physical manipulation of stem cells to growth factor treatment, genetic manipulation, and chemical and pharmacological treatment, each strategy having advantages and limitations. Most of these pre-treatment protocols are non-combinative. This editorial is a continuum of Li <i>et al</i>'s published article and Wan <i>et al</i>'s editorial focusing on the significance of pre-treatment strategies to enhance their stemness, immunoregulatory, and immunosuppressive properties. They have elaborated on the intricacies of the combinative pre-treatment protocol using pro-inflammatory cytokines and hypoxia. Applying a well-defined multi-pronged combinatorial strategy of mesenchymal stem cells (MSCs), pre-treatment based on the mechanistic understanding is expected to develop \"Super MSCs\", which will create a transformative shift in MSC-based therapies in clinical settings, potentially revolutionizing the field. Once optimized, the standardized protocols may be used with slight modifications to pre-treat different stem cells to develop \"super stem cells\" with augmented stemness, functionality, and reparability for diverse clinical applications with better outcomes.</p>","PeriodicalId":23775,"journal":{"name":"World journal of stem cells","volume":"16 6","pages":"623-640"},"PeriodicalIF":3.6,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11212549/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141471114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
RPLP0/TBP are the most stable reference genes for human dental pulp stem cells under osteogenic differentiation. RPLP0/TBP是人牙髓干细胞成骨分化过程中最稳定的参考基因。
IF 3.6 3区 医学 Q3 CELL & TISSUE ENGINEERING Pub Date : 2024-06-26 DOI: 10.4252/wjsc.v16.i6.656
Daniel B Ferreira, Leticia M Gasparoni, Cristiane F Bronzeri, Katiucia B S Paiva

Background: Validation of the reference gene (RG) stability during experimental analyses is essential for correct quantitative real-time polymerase chain reaction (RT-qPCR) data normalisation. Commonly, in an unreliable way, several studies use genes involved in essential cellular functions [glyceraldehyde-3-phosphate dehydrogenase (GAPDH), 18S rRNA, and β-actin] without paying attention to whether they are suitable for such experimental conditions or the reason for choosing such genes. Furthermore, such studies use only one gene when Minimum Information for Publication of Quantitative Real-Time PCR Experiments guidelines recommend two or more genes. It impacts the credibility of these studies and causes distortions in the gene expression findings. For tissue engineering, the accuracy of gene expression drives the best experimental or therapeutical approaches.

Aim: To verify the most stable RG during osteogenic differentiation of human dental pulp stem cells (DPSCs) by RT-qPCR.

Methods: We cultivated DPSCs under two conditions: Undifferentiated and osteogenic differentiation, both for 35 d. We evaluated the gene expression of 10 candidates for RGs [ribosomal protein, large, P0 (RPLP0), TATA-binding protein (TBP), GAPDH, actin beta (ACTB), tubulin (TUB), aminolevulinic acid synthase 1 (ALAS1), tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, zeta (YWHAZ), eukaryotic translational elongation factor 1 alpha (EF1a), succinate dehydrogenase complex, subunit A, flavoprotein (SDHA), and beta-2-microglobulin (B2M)] every 7 d (1, 7, 14, 21, 28, and 35 d) by RT-qPCR. The data were analysed by the four main algorithms, ΔCt method, geNorm, NormFinder, and BestKeeper and ranked by the RefFinder method. We subdivided the samples into eight subgroups.

Results: All of the data sets from clonogenic and osteogenic samples were analysed using the RefFinder algorithm. The final ranking showed RPLP0/TBP as the two most stable RGs and TUB/B2M as the two least stable RGs. Either the ΔCt method or NormFinder analysis showed TBP/RPLP0 as the two most stable genes. However, geNorm analysis showed RPLP0/EF1α in the first place. These algorithms' two least stable RGs were B2M/GAPDH. For BestKeeper, ALAS1 was ranked as the most stable RG, and SDHA as the least stable RG. The pair RPLP0/TBP was detected in most subgroups as the most stable RGs, following the RefFinfer ranking.

Conclusion: For the first time, we show that RPLP0/TBP are the most stable RGs, whereas TUB/B2M are unstable RGs for long-term osteogenic differentiation of human DPSCs in traditional monolayers.

背景:在实验分析过程中验证参考基因(RG)的稳定性对于正确的实时定量聚合酶链反应(RT-qPCR)数据归一化至关重要。一些研究通常以不可靠的方式使用涉及细胞基本功能的基因[甘油醛-3-磷酸脱氢酶(GAPDH)、18S rRNA 和 β-肌动蛋白],而不注意这些基因是否适合此类实验条件或选择此类基因的原因。此外,这些研究只使用了一种基因,而《定量 Real-Time PCR 实验发表的最低限度信息》指南建议使用两种或两种以上的基因。这影响了这些研究的可信度,并导致基因表达结果失真。对于组织工程学而言,基因表达的准确性是最佳实验或治疗方法的驱动力。目的:通过 RT-qPCR 验证人牙髓干细胞(DPSCs)成骨分化过程中最稳定的 RG:方法:我们在两种条件下培养牙髓干细胞:方法:我们在两种条件下培养牙髓干细胞:未分化和成骨分化,培养时间均为35 d。我们评估了 10 种候选 RGs(核糖体蛋白,大,P0 (RPLP0)、TATA 结合蛋白 (TBP)、GAPDH、肌动蛋白 beta (ACTB)、微管蛋白 (TUB)、氨基乙酰丙酸合成酶 1 (ALAS1)、酪氨酸 3-单加氧酶/色氨酸 5-单加氧酶活化蛋白、zeta(YWHAZ)、真核翻译伸长因子 1 alpha(EF1a)、琥珀酸脱氢酶复合物亚基 A、黄素蛋白(SDHA)和 beta-2-微球蛋白(B2M)],每 7 天(1、7、14、21、28 和 35 天)通过 RT-qPCR 检测一次。数据采用四种主要算法(ΔCt 法、geNorm 法、NormFinder 法和 BestKeeper 法)进行分析,并采用 RefFinder 法进行排序。我们将样本细分为八个子组:结果:使用 RefFinder 算法分析了克隆和成骨样本的所有数据集。最终排名显示,RPLP0/TBP 是两个最稳定的 RG,TUB/B2M 是两个最不稳定的 RG。ΔCt方法或NormFinder分析都显示TBP/RPLP0是两个最稳定的基因。然而,geNorm 分析显示 RPLP0/EF1α 排在首位。这些算法中最不稳定的两个 RG 是 B2M/GAPDH。在 BestKeeper 中,ALAS1 被评为最稳定的 RG,SDHA 被评为最不稳定的 RG。在大多数分组中,RPLP0/TBP 对被检测为最稳定的 RG,这与 RefFinfer 的排名一致:结论:我们首次发现 RPLP0/TBP 是最稳定的 RG,而 TUB/B2M 是不稳定的 RG,可用于人类 DPSCs 在传统单层中的长期成骨分化。
{"title":"RPLP0/TBP are the most stable reference genes for human dental pulp stem cells under osteogenic differentiation.","authors":"Daniel B Ferreira, Leticia M Gasparoni, Cristiane F Bronzeri, Katiucia B S Paiva","doi":"10.4252/wjsc.v16.i6.656","DOIUrl":"10.4252/wjsc.v16.i6.656","url":null,"abstract":"<p><strong>Background: </strong>Validation of the reference gene (RG) stability during experimental analyses is essential for correct quantitative real-time polymerase chain reaction (RT-qPCR) data normalisation. Commonly, in an unreliable way, several studies use genes involved in essential cellular functions [glyceraldehyde-3-phosphate dehydrogenase (GAPDH), 18S rRNA, and β-actin] without paying attention to whether they are suitable for such experimental conditions or the reason for choosing such genes. Furthermore, such studies use only one gene when Minimum Information for Publication of Quantitative Real-Time PCR Experiments guidelines recommend two or more genes. It impacts the credibility of these studies and causes distortions in the gene expression findings. For tissue engineering, the accuracy of gene expression drives the best experimental or therapeutical approaches.</p><p><strong>Aim: </strong>To verify the most stable RG during osteogenic differentiation of human dental pulp stem cells (DPSCs) by RT-qPCR.</p><p><strong>Methods: </strong>We cultivated DPSCs under two conditions: Undifferentiated and osteogenic differentiation, both for 35 d. We evaluated the gene expression of 10 candidates for RGs [ribosomal protein, large, P0 (<i>RPLP0</i>), TATA-binding protein (<i>TBP</i>), <i>GAPDH</i>, actin beta (<i>ACTB</i>), tubulin (<i>TUB</i>), aminolevulinic acid synthase 1 (<i>ALAS1</i>), tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, zeta (<i>YWHAZ</i>), eukaryotic translational elongation factor 1 alpha (<i>EF1a</i>), succinate dehydrogenase complex, subunit A, flavoprotein (<i>SDHA</i>), and beta-2-microglobulin (<i>B2M</i>)] every 7 d (1, 7, 14, 21, 28, and 35 d) by RT-qPCR. The data were analysed by the four main algorithms, ΔCt method, geNorm, NormFinder, and BestKeeper and ranked by the RefFinder method. We subdivided the samples into eight subgroups.</p><p><strong>Results: </strong>All of the data sets from clonogenic and osteogenic samples were analysed using the RefFinder algorithm. The final ranking showed RPLP0/TBP as the two most stable RGs and TUB/B2M as the two least stable RGs. Either the ΔCt method or NormFinder analysis showed TBP/RPLP0 as the two most stable genes. However, geNorm analysis showed RPLP0/EF1α in the first place. These algorithms' two least stable RGs were B2M/GAPDH. For BestKeeper, ALAS1 was ranked as the most stable RG, and SDHA as the least stable RG. The pair RPLP0/TBP was detected in most subgroups as the most stable RGs, following the RefFinfer ranking.</p><p><strong>Conclusion: </strong>For the first time, we show that RPLP0/TBP are the most stable RGs, whereas TUB/B2M are unstable RGs for long-term osteogenic differentiation of human DPSCs in traditional monolayers.</p>","PeriodicalId":23775,"journal":{"name":"World journal of stem cells","volume":"16 6","pages":"656-669"},"PeriodicalIF":3.6,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11212553/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141471115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Role of glioma stem cells in promoting tumor chemo- and radioresistance: A systematic review of potential targeted treatments. 胶质瘤干细胞在促进肿瘤化疗和放射抗药性方面的作用:潜在靶向治疗的系统回顾。
IF 4.1 3区 医学 Q3 CELL & TISSUE ENGINEERING Pub Date : 2024-05-26 DOI: 10.4252/wjsc.v16.i5.604
Edoardo Agosti, Marco Zeppieri, Mattia Ghidoni, Tamara Ius, Alessandro Tel, Marco Maria Fontanella, Pier Paolo Panciani
<p><strong>Background: </strong>Gliomas pose a significant challenge to effective treatment despite advancements in chemotherapy and radiotherapy. Glioma stem cells (GSCs), a subset within tumors, contribute to resistance, tumor heterogeneity, and plasticity. Recent studies reveal GSCs' role in therapeutic resistance, driven by DNA repair mechanisms and dynamic transitions between cellular states. Resistance mechanisms can involve different cellular pathways, most of which have been recently reported in the literature. Despite progress, targeted therapeutic approaches lack consensus due to GSCs' high plasticity.</p><p><strong>Aim: </strong>To analyze targeted therapies against GSC-mediated resistance to radio- and chemotherapy in gliomas, focusing on underlying mechanisms.</p><p><strong>Methods: </strong>A systematic search was conducted across major medical databases (PubMed, Embase, and Cochrane Library) up to September 30, 2023. The search strategy utilized relevant Medical Subject Heading terms and keywords related to including "glioma stem cells", "radiotherapy", "chemotherapy", "resistance", and "targeted therapies". Studies included in this review were publications focusing on targeted therapies against the molecular mechanism of GSC-mediated resistance to radiotherapy resistance (RTR).</p><p><strong>Results: </strong>In a comprehensive review of 66 studies on stem cell therapies for SCI, 452 papers were initially identified, with 203 chosen for full-text analysis. Among them, 201 were deemed eligible after excluding 168 for various reasons. The temporal breakdown of studies illustrates this trend: 2005-2010 (33.3%), 2011-2015 (36.4%), and 2016-2022 (30.3%). Key GSC models, particularly U87 (33.3%), U251 (15.2%), and T98G (15.2%), emerge as significant in research, reflecting their representativeness of glioma characteristics. Pathway analysis indicates a focus on phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (mTOR) (27.3%) and Notch (12.1%) pathways, suggesting their crucial roles in resistance development. Targeted molecules with mTOR (18.2%), CHK1/2 (15.2%), and ATP binding cassette G2 (12.1%) as frequent targets underscore their importance in overcoming GSC-mediated resistance. Various therapeutic agents, notably RNA inhibitor/short hairpin RNA (27.3%), inhibitors (<i>e.g.,</i> LY294002, NVP-BEZ235) (24.2%), and monoclonal antibodies (<i>e.g.,</i> cetuximab) (9.1%), demonstrate versatility in targeted therapies. among 20 studies (60.6%), the most common effect on the chemotherapy resistance response is a reduction in temozolomide resistance (51.5%), followed by reductions in carmustine resistance (9.1%) and doxorubicin resistance (3.0%), while resistance to RTR is reduced in 42.4% of studies.</p><p><strong>Conclusion: </strong>GSCs play a complex role in mediating radioresistance and chemoresistance, emphasizing the necessity for precision therapies that consider the heterogeneity within the GSC population an
背景:尽管化疗和放疗取得了进展,但胶质瘤对有效治疗构成了巨大挑战。胶质瘤干细胞(GSCs)是肿瘤中的一个亚群,它对抗药性、肿瘤异质性和可塑性做出了贡献。最近的研究揭示了神经胶质瘤干细胞在治疗耐药性中的作用,其驱动力来自DNA修复机制和细胞状态之间的动态转换。耐药机制可能涉及不同的细胞通路,其中大部分已在最近的文献中报道。目的:分析针对GSC介导的胶质瘤放疗和化疗耐药性的靶向疗法,重点关注其潜在机制:方法:对截至 2023 年 9 月 30 日的主要医学数据库(PubMed、Embase 和 Cochrane Library)进行了系统检索。检索策略使用了相关的医学主题词和关键词,包括 "胶质瘤干细胞"、"放疗"、"化疗"、"抗药性 "和 "靶向疗法"。纳入本综述的研究是针对GSC介导的放疗耐药性(RTR)分子机制的靶向疗法的出版物:在对66项有关SCI干细胞疗法的研究进行的全面综述中,初步确定了452篇论文,并选择了203篇进行全文分析。由于各种原因,其中168篇被排除,201篇被认为符合条件。研究的时间细分说明了这一趋势:2005-2010年(33.3%)、2011-2015年(36.4%)和2016-2022年(30.3%)。主要的 GSC 模型,尤其是 U87(33.3%)、U251(15.2%)和 T98G(15.2%),在研究中具有重要意义,反映了它们在胶质瘤特征方面的代表性。通路分析表明,磷酸肌酸 3- 激酶/蛋白激酶 B/哺乳动物雷帕霉素靶标(mTOR)(27.3%)和诺奇(Notch)(12.1%)通路是研究的重点,表明它们在耐药性发展中起着关键作用。以mTOR(18.2%)、CHK1/2(15.2%)和ATP结合盒G2(12.1%)为常见靶点的靶向分子强调了它们在克服GSC介导的耐药性方面的重要性。各种治疗药物,特别是 RNA 抑制剂/短发夹 RNA(27.3%)、抑制剂(如 LY294002、NVP-BEZ235)(24.2%)和单克隆抗体(如西妥昔单抗)(9.1%),都是 GSC 耐药的主要靶点、在 20 项研究(60.6%)中,对化疗耐药性反应最常见的影响是替莫唑胺耐药性的降低(51.5%),其次是卡莫司汀耐药性的降低(9.1%)和多柔比星耐药性的降低(3.0%),而 42.4% 的研究降低了对 RTR 的耐药性:结论:GSCs在介导放射耐药性和化疗耐药性方面发挥着复杂的作用,强调了精准疗法的必要性,这种疗法应考虑到GSC群体内部的异质性和动态的肿瘤微环境,以提高胶质母细胞瘤患者的治疗效果。
{"title":"Role of glioma stem cells in promoting tumor chemo- and radioresistance: A systematic review of potential targeted treatments.","authors":"Edoardo Agosti, Marco Zeppieri, Mattia Ghidoni, Tamara Ius, Alessandro Tel, Marco Maria Fontanella, Pier Paolo Panciani","doi":"10.4252/wjsc.v16.i5.604","DOIUrl":"10.4252/wjsc.v16.i5.604","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Gliomas pose a significant challenge to effective treatment despite advancements in chemotherapy and radiotherapy. Glioma stem cells (GSCs), a subset within tumors, contribute to resistance, tumor heterogeneity, and plasticity. Recent studies reveal GSCs' role in therapeutic resistance, driven by DNA repair mechanisms and dynamic transitions between cellular states. Resistance mechanisms can involve different cellular pathways, most of which have been recently reported in the literature. Despite progress, targeted therapeutic approaches lack consensus due to GSCs' high plasticity.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Aim: &lt;/strong&gt;To analyze targeted therapies against GSC-mediated resistance to radio- and chemotherapy in gliomas, focusing on underlying mechanisms.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A systematic search was conducted across major medical databases (PubMed, Embase, and Cochrane Library) up to September 30, 2023. The search strategy utilized relevant Medical Subject Heading terms and keywords related to including \"glioma stem cells\", \"radiotherapy\", \"chemotherapy\", \"resistance\", and \"targeted therapies\". Studies included in this review were publications focusing on targeted therapies against the molecular mechanism of GSC-mediated resistance to radiotherapy resistance (RTR).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;In a comprehensive review of 66 studies on stem cell therapies for SCI, 452 papers were initially identified, with 203 chosen for full-text analysis. Among them, 201 were deemed eligible after excluding 168 for various reasons. The temporal breakdown of studies illustrates this trend: 2005-2010 (33.3%), 2011-2015 (36.4%), and 2016-2022 (30.3%). Key GSC models, particularly U87 (33.3%), U251 (15.2%), and T98G (15.2%), emerge as significant in research, reflecting their representativeness of glioma characteristics. Pathway analysis indicates a focus on phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (mTOR) (27.3%) and Notch (12.1%) pathways, suggesting their crucial roles in resistance development. Targeted molecules with mTOR (18.2%), CHK1/2 (15.2%), and ATP binding cassette G2 (12.1%) as frequent targets underscore their importance in overcoming GSC-mediated resistance. Various therapeutic agents, notably RNA inhibitor/short hairpin RNA (27.3%), inhibitors (&lt;i&gt;e.g.,&lt;/i&gt; LY294002, NVP-BEZ235) (24.2%), and monoclonal antibodies (&lt;i&gt;e.g.,&lt;/i&gt; cetuximab) (9.1%), demonstrate versatility in targeted therapies. among 20 studies (60.6%), the most common effect on the chemotherapy resistance response is a reduction in temozolomide resistance (51.5%), followed by reductions in carmustine resistance (9.1%) and doxorubicin resistance (3.0%), while resistance to RTR is reduced in 42.4% of studies.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;GSCs play a complex role in mediating radioresistance and chemoresistance, emphasizing the necessity for precision therapies that consider the heterogeneity within the GSC population an","PeriodicalId":23775,"journal":{"name":"World journal of stem cells","volume":"16 5","pages":"604-614"},"PeriodicalIF":4.1,"publicationDate":"2024-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11135247/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141180881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
World journal of stem cells
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1