首页 > 最新文献

Regenerative Therapy最新文献

英文 中文
Canine adipose-derived mesenchymal stromal cells inhibit the growth of canine hematologic malignancy cell lines
IF 3.4 3区 环境科学与生态学 Q3 CELL & TISSUE ENGINEERING Pub Date : 2025-01-04 DOI: 10.1016/j.reth.2024.12.019
Yuyo Yasumura , Takahiro Teshima , Tomokazu Nagashima , Masaki Michishita , Hiroki Shigechika , Yoshiaki Taira , Ryohei Suzuki , Hirotaka Matsumoto

Introduction

Intestinal lymphoma may be latent in some dogs with chronic inflammatory enteropathy. Mesenchymal stromal cells (MSCs) have potential therapeutic applications for refractory chronic inflammatory enteropathy, but their impact on the development of potential intestinal lymphomas has not yet been evaluated. Therefore, this study was performed to investigate the effect of canine adipose-derived MSCs (cADSCs) on the growth of canine lymphoma cell lines to assess the safety of MSC-based therapy in terms of pro- and anti-tumorigenic effects.

Methods

CADSCs were co-cultured with canine lymphoma/leukemia cell lines of various lineages, with or without cell-to-cell contact, to evaluate their effects on proliferation, apoptosis, and cell cycle progression in vitro. Additionally, a bioluminescent canine lymphoma cell line, established through firefly luciferase transduction, was co-injected with varying doses of cADSCs into immunocompromised mice. The growth of canine lymphoma cells was monitored over time in vivo using bioluminescence imaging.

Results

CADSCs inhibited the proliferation of all canine lymphoma/leukemia cell lines in a dose-dependent manner in vitro, under conditions allowing cell-to-cell contact. This inhibition occurred via the induction of apoptosis, G0/G1 phase cell cycle arrest, or both mechanisms. However, these effects were lost when the cells were physically separated using Transwell inserts. In xenotransplantation mouse models, cADSCs dose-dependently inhibited canine lymphoma cell growth and lung metastasis, as indicated by reduced bioluminescence signals.

Conclusions

This study has demonstrated for the first time that cADSCs inhibit the growth of different lineages of canine lymphoma/leukemia cells both in vitro and in vivo. These findings suggest that MSC-based cell therapy could potentially be applied to canine chronic inflammatory enteropathy without increasing the risk of promoting the growth of latent intestinal lymphomas.
{"title":"Canine adipose-derived mesenchymal stromal cells inhibit the growth of canine hematologic malignancy cell lines","authors":"Yuyo Yasumura ,&nbsp;Takahiro Teshima ,&nbsp;Tomokazu Nagashima ,&nbsp;Masaki Michishita ,&nbsp;Hiroki Shigechika ,&nbsp;Yoshiaki Taira ,&nbsp;Ryohei Suzuki ,&nbsp;Hirotaka Matsumoto","doi":"10.1016/j.reth.2024.12.019","DOIUrl":"10.1016/j.reth.2024.12.019","url":null,"abstract":"<div><h3>Introduction</h3><div>Intestinal lymphoma may be latent in some dogs with chronic inflammatory enteropathy. Mesenchymal stromal cells (MSCs) have potential therapeutic applications for refractory chronic inflammatory enteropathy, but their impact on the development of potential intestinal lymphomas has not yet been evaluated. Therefore, this study was performed to investigate the effect of canine adipose-derived MSCs (cADSCs) on the growth of canine lymphoma cell lines to assess the safety of MSC-based therapy in terms of pro- and anti-tumorigenic effects.</div></div><div><h3>Methods</h3><div>CADSCs were co-cultured with canine lymphoma/leukemia cell lines of various lineages, with or without cell-to-cell contact, to evaluate their effects on proliferation, apoptosis, and cell cycle progression in vitro. Additionally, a bioluminescent canine lymphoma cell line, established through firefly luciferase transduction, was co-injected with varying doses of cADSCs into immunocompromised mice. The growth of canine lymphoma cells was monitored over time in vivo using bioluminescence imaging.</div></div><div><h3>Results</h3><div>CADSCs inhibited the proliferation of all canine lymphoma/leukemia cell lines in a dose-dependent manner in vitro, under conditions allowing cell-to-cell contact. This inhibition occurred via the induction of apoptosis, G0/G1 phase cell cycle arrest, or both mechanisms. However, these effects were lost when the cells were physically separated using Transwell inserts. In xenotransplantation mouse models, cADSCs dose-dependently inhibited canine lymphoma cell growth and lung metastasis, as indicated by reduced bioluminescence signals.</div></div><div><h3>Conclusions</h3><div>This study has demonstrated for the first time that cADSCs inhibit the growth of different lineages of canine lymphoma/leukemia cells both in vitro and in vivo. These findings suggest that MSC-based cell therapy could potentially be applied to canine chronic inflammatory enteropathy without increasing the risk of promoting the growth of latent intestinal lymphomas.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"28 ","pages":"Pages 301-313"},"PeriodicalIF":3.4,"publicationDate":"2025-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11757230/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143047733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Systemic administration of induced pluripotent stem cell-derived mesenchymal stem cells improves cardiac function through extracellular vesicle-mediated tissue repair in a rat model of ischemic cardiomyopathy 在缺血性心肌病大鼠模型中,系统给予诱导多能干细胞衍生的间充质干细胞通过细胞外囊泡介导的组织修复改善心功能。
IF 3.4 3区 环境科学与生态学 Q3 CELL & TISSUE ENGINEERING Pub Date : 2024-12-31 DOI: 10.1016/j.reth.2024.12.008
Ryo Kawasumi , Takuji Kawamura , Kizuku Yamashita , Yuji Tominaga , Akima Harada , Emiko Ito , Maki Takeda , Shunbun Kita , Iichiro Shimomura , Shigeru Miyagawa

Introduction

Systemic administration of induced pluripotent stem cell-derived mesenchymal stem cells (iPS-MSCs) has a therapeutic effect on myocardial ischemia. However, the therapeutic mechanism underlying systemic iPS-MSC-based therapy for ischemic cardiomyopathy (ICM) remains unclear. We investigated the therapeutic effects of iPS-MSCs through extracellular vesicle (EV)-mediated tissue repair in a rat model of ICM.

Methods

A rat ICM model was created by left anterior descending coronary artery ligation. iPS-MSCs were administered intravenously every week for four weeks in the iPS-MSC group, whereas saline was administered to the control group. Alix, a protein involved in the biogenesis of EVs, was knocked down, and Alix-knockdown iPS-MSCs were administered to the siAlix group. We analyzed sequential cardiac function using echocardiography, histological analysis, cell tracking analysis with fluorescent dyes, and comprehensive RNA sequencing of the border zone of the myocardium after treatment.

Results

Left ventricular ejection fraction (LVEF) was significantly improved in the iPS-MSC group compared with that in the control group. In the siAlix group, LVEF was significantly lower than that in the iPS-MSC group. Histological analysis showed a significant decrease in fibrosis area and significant increase in microvascular density in the iPS-MSC group. A cell-tracking assay revealed iPS-MSC accumulation in the border zone of the myocardium during the acute phase. Comprehensive microRNA sequencing analysis revealed that EVs from iPS-MSCs contained miRNAs associated with anti-fibrosis and angiogenesis. Gene ontology analysis of differentially expressed genes in myocardial tissue also showed upregulation of pathways related to antifibrosis and neovascularization and downregulation of pathways linked to inflammation and T-cell differentiation.

Conclusions

Systemic administration of iPS-MSCs improved cardiac function through EV-mediated angiogenetic and antifibrotic effects in an ICM, suggesting the clinical possibility of treating chronic heart failure.
导论:系统给药诱导多能干细胞衍生间充质干细胞(iPS-MSCs)对心肌缺血有治疗作用。然而,基于ips - msc的系统性缺血性心肌病(ICM)治疗的治疗机制尚不清楚。我们通过细胞外囊泡(EV)介导的组织修复研究了iPS-MSCs在大鼠ICM模型中的治疗作用。方法:采用左冠状动脉前降支结扎法建立大鼠ICM模型。iPS-MSC组每周静脉注射iPS-MSC,持续四周,而对照组则给予生理盐水。将参与EVs生物发生的蛋白Alix敲除,并将敲除Alix的iPS-MSCs给予siAlix组。我们使用超声心动图、组织学分析、荧光染料细胞跟踪分析和治疗后心肌边界区综合RNA测序分析序贯心功能。结果:与对照组相比,iPS-MSC组左室射血分数(LVEF)明显改善。siAlix组LVEF明显低于iPS-MSC组。组织学分析显示,iPS-MSC组纤维化面积明显减少,微血管密度明显增加。细胞跟踪实验显示急性期心肌边界区有iPS-MSC积累。综合microRNA测序分析显示,来自iPS-MSCs的ev含有与抗纤维化和血管生成相关的mirna。对心肌组织中差异表达基因的基因本体论分析也显示,与抗纤维化和新生血管相关的通路上调,与炎症和t细胞分化相关的通路下调。结论:全身给药iPS-MSCs通过ev介导的血管生成和抗纤维化作用改善ICM心功能,提示治疗慢性心力衰竭的临床可能性。
{"title":"Systemic administration of induced pluripotent stem cell-derived mesenchymal stem cells improves cardiac function through extracellular vesicle-mediated tissue repair in a rat model of ischemic cardiomyopathy","authors":"Ryo Kawasumi ,&nbsp;Takuji Kawamura ,&nbsp;Kizuku Yamashita ,&nbsp;Yuji Tominaga ,&nbsp;Akima Harada ,&nbsp;Emiko Ito ,&nbsp;Maki Takeda ,&nbsp;Shunbun Kita ,&nbsp;Iichiro Shimomura ,&nbsp;Shigeru Miyagawa","doi":"10.1016/j.reth.2024.12.008","DOIUrl":"10.1016/j.reth.2024.12.008","url":null,"abstract":"<div><h3>Introduction</h3><div>Systemic administration of induced pluripotent stem cell-derived mesenchymal stem cells (iPS-MSCs) has a therapeutic effect on myocardial ischemia. However, the therapeutic mechanism underlying systemic iPS-MSC-based therapy for ischemic cardiomyopathy (ICM) remains unclear. We investigated the therapeutic effects of iPS-MSCs through extracellular vesicle (EV)-mediated tissue repair in a rat model of ICM.</div></div><div><h3>Methods</h3><div>A rat ICM model was created by left anterior descending coronary artery ligation. iPS-MSCs were administered intravenously every week for four weeks in the iPS-MSC group, whereas saline was administered to the control group. Alix, a protein involved in the biogenesis of EVs, was knocked down, and Alix-knockdown iPS-MSCs were administered to the siAlix group. We analyzed sequential cardiac function using echocardiography, histological analysis, cell tracking analysis with fluorescent dyes, and comprehensive RNA sequencing of the border zone of the myocardium after treatment.</div></div><div><h3>Results</h3><div>Left ventricular ejection fraction (LVEF) was significantly improved in the iPS-MSC group compared with that in the control group. In the siAlix group, LVEF was significantly lower than that in the iPS-MSC group. Histological analysis showed a significant decrease in fibrosis area and significant increase in microvascular density in the iPS-MSC group. A cell-tracking assay revealed iPS-MSC accumulation in the border zone of the myocardium during the acute phase. Comprehensive microRNA sequencing analysis revealed that EVs from iPS-MSCs contained miRNAs associated with anti-fibrosis and angiogenesis. Gene ontology analysis of differentially expressed genes in myocardial tissue also showed upregulation of pathways related to antifibrosis and neovascularization and downregulation of pathways linked to inflammation and T-cell differentiation.</div></div><div><h3>Conclusions</h3><div>Systemic administration of iPS-MSCs improved cardiac function through EV-mediated angiogenetic and antifibrotic effects in an ICM, suggesting the clinical possibility of treating chronic heart failure.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"28 ","pages":"Pages 253-261"},"PeriodicalIF":3.4,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11745812/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143010648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Viral-based gene therapy clinical trials for immune deficiencies and blood disorders from 2013 until 2023 - an overview
IF 3.4 3区 环境科学与生态学 Q3 CELL & TISSUE ENGINEERING Pub Date : 2024-12-31 DOI: 10.1016/j.reth.2024.12.007
Shirin Eshghi , Mahsa Mousakhan Bakhtiari , Maryam Behfar , Elaheh Izadi , Parisa Naji , Leila Jafari , Rashin Mohseni , Zohreh Saltanatpour , Amir Ali Hamidieh
Gene therapy (GT) as a groundbreaking approach holds promise for treating many diseases including immune deficiencies and blood disorders. GT can benefit patients suffering from these diseases, especially those without matched donors or who are at risk after hematopoietic stem cell transplantation (HSCT). Due to all the advances in the field of GT, its main challenge is still gene delivery. Generally, gene delivery systems are categorized into two types depending on utilized vectors: non-viral and viral. Viral vectors are commonly used in GT because of their high efficiency compared to non-viral vectors. In this article, all clinical trials on viral-based GT (with the exclusion of CRISPR and CAR-T cell Therapy) in the last decade for immune deficiencies and blood disorders including Severe combined immune deficiency (SCID), Wiskott-Aldrich syndrome (WAS), Chronic granulomatous disease (CGD), Leukocyte adhesion deficiency (LAD), Fanconi anemia (FA), Hemoglobinopathies, and Hemophilia will thoroughly be discussed. Moreover, viral vectors used in these trials including Retroviruses (RVs), Lentiviruses (LVs), and Adeno-Associated Viruses (AAVs) will be reviewed. This review provides a concise overview of traditional treatments for the mentioned disease and precise details of their viral-based GT clinical trial studies in the last decade, then presents the advantages, disadvantages, and potential adverse events of GT. In conclusion, this review presents GT as a hopeful and growing field in healthcare that could offer cures to diseases that were previously thought to be untreatable.
{"title":"Viral-based gene therapy clinical trials for immune deficiencies and blood disorders from 2013 until 2023 - an overview","authors":"Shirin Eshghi ,&nbsp;Mahsa Mousakhan Bakhtiari ,&nbsp;Maryam Behfar ,&nbsp;Elaheh Izadi ,&nbsp;Parisa Naji ,&nbsp;Leila Jafari ,&nbsp;Rashin Mohseni ,&nbsp;Zohreh Saltanatpour ,&nbsp;Amir Ali Hamidieh","doi":"10.1016/j.reth.2024.12.007","DOIUrl":"10.1016/j.reth.2024.12.007","url":null,"abstract":"<div><div>Gene therapy (GT) as a groundbreaking approach holds promise for treating many diseases including immune deficiencies and blood disorders. GT can benefit patients suffering from these diseases, especially those without matched donors or who are at risk after hematopoietic stem cell transplantation (HSCT). Due to all the advances in the field of GT, its main challenge is still gene delivery. Generally, gene delivery systems are categorized into two types depending on utilized vectors: non-viral and viral. Viral vectors are commonly used in GT because of their high efficiency compared to non-viral vectors. In this article, all clinical trials on viral-based GT (with the exclusion of CRISPR and CAR-T cell Therapy) in the last decade for immune deficiencies and blood disorders including Severe combined immune deficiency (SCID), Wiskott-Aldrich syndrome (WAS), Chronic granulomatous disease (CGD), Leukocyte adhesion deficiency (LAD), Fanconi anemia (FA), Hemoglobinopathies, and Hemophilia will thoroughly be discussed. Moreover, viral vectors used in these trials including Retroviruses (RVs), Lentiviruses (LVs), and Adeno-Associated Viruses (AAVs) will be reviewed. This review provides a concise overview of traditional treatments for the mentioned disease and precise details of their viral-based GT clinical trial studies in the last decade, then presents the advantages, disadvantages, and potential adverse events of GT. In conclusion, this review presents GT as a hopeful and growing field in healthcare that could offer cures to diseases that were previously thought to be untreatable.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"28 ","pages":"Pages 262-279"},"PeriodicalIF":3.4,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11751425/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143024671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Interplay between pioneer transcription factors and epigenetic modifiers in cell reprogramming 细胞重编程中先锋转录因子与表观遗传修饰因子的相互作用。
IF 3.4 3区 环境科学与生态学 Q3 CELL & TISSUE ENGINEERING Pub Date : 2024-12-30 DOI: 10.1016/j.reth.2024.12.014
Gerardo Mirizio , Samuel Sampson , Makiko Iwafuchi
The generation of induced pluripotent stem cells (iPSCs) from differentiated somatic cells by Yamanaka factors, including pioneer transcription factors (TFs), has greatly reshaped our traditional understanding of cell plasticity and demonstrated the remarkable potential of pioneer TFs. In addition to iPSC reprogramming, pioneer TFs are pivotal in direct reprogramming or transdifferentiation where somatic cells are converted into different cell types without passing through a pluripotent state. Pioneer TFs initiate a reprogramming process through chromatin opening, thereby establishing competence for new gene regulatory programs. The action of pioneer TFs is both influenced by and exerts influence on epigenetic regulation. Despite significant advances, many direct reprogramming processes remain inefficient, which limits their reliability for clinical applications. In this review, we discuss the molecular mechanisms underlying pioneer TF-driven reprogramming, with a focus on their interactions with epigenetic modifiers, including Polycomb repressive complexes (PRCs), nucleosome remodeling and deacetylase (NuRD) complexes, and the DNA methylation machinery. A deeper understanding of the dynamic interplay between pioneer TFs and epigenetic modifiers will be essential for advancing reprogramming technologies and unlocking their full clinical potential.
利用Yamanaka因子(包括先锋转录因子)从分化的体细胞中生成诱导多能干细胞(iPSCs),极大地重塑了我们对细胞可塑性的传统认识,并展示了先锋转录因子的巨大潜力。除了iPSC重编程,先锋tf在直接重编程或转分化中起关键作用,其中体细胞在不经过多能状态的情况下转化为不同的细胞类型。先锋tf通过染色质打开启动重编程过程,从而建立新的基因调控程序的能力。先锋tf的作用既受表观遗传调控的影响,又对表观遗传调控产生影响。尽管取得了重大进展,但许多直接重编程过程仍然效率低下,这限制了它们在临床应用中的可靠性。在这篇综述中,我们讨论了先锋tf驱动重编程的分子机制,重点讨论了它们与表观遗传修饰因子的相互作用,包括Polycomb抑制复合物(PRCs)、核小体重塑和去乙酰化酶(NuRD)复合物以及DNA甲基化机制。更深入地了解先锋tf和表观遗传修饰因子之间的动态相互作用,对于推进重编程技术和释放其全部临床潜力至关重要。
{"title":"Interplay between pioneer transcription factors and epigenetic modifiers in cell reprogramming","authors":"Gerardo Mirizio ,&nbsp;Samuel Sampson ,&nbsp;Makiko Iwafuchi","doi":"10.1016/j.reth.2024.12.014","DOIUrl":"10.1016/j.reth.2024.12.014","url":null,"abstract":"<div><div>The generation of induced pluripotent stem cells (iPSCs) from differentiated somatic cells by Yamanaka factors, including pioneer transcription factors (TFs), has greatly reshaped our traditional understanding of cell plasticity and demonstrated the remarkable potential of pioneer TFs. In addition to iPSC reprogramming, pioneer TFs are pivotal in direct reprogramming or transdifferentiation where somatic cells are converted into different cell types without passing through a pluripotent state. Pioneer TFs initiate a reprogramming process through chromatin opening, thereby establishing competence for new gene regulatory programs. The action of pioneer TFs is both influenced by and exerts influence on epigenetic regulation. Despite significant advances, many direct reprogramming processes remain inefficient, which limits their reliability for clinical applications. In this review, we discuss the molecular mechanisms underlying pioneer TF-driven reprogramming, with a focus on their interactions with epigenetic modifiers, including Polycomb repressive complexes (PRCs), nucleosome remodeling and deacetylase (NuRD) complexes, and the DNA methylation machinery. A deeper understanding of the dynamic interplay between pioneer TFs and epigenetic modifiers will be essential for advancing reprogramming technologies and unlocking their full clinical potential.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"28 ","pages":"Pages 246-252"},"PeriodicalIF":3.4,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11745816/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143010686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Novel preparation of laponite based theranostic silver nanocomposite for drug delivery, radical scavenging and healing efficiency for wound care management after surgery 新型制备的拉脱石基治疗银纳米复合材料用于手术后伤口护理管理的药物输送、自由基清除和愈合效率。
IF 3.4 3区 环境科学与生态学 Q3 CELL & TISSUE ENGINEERING Pub Date : 2024-12-30 DOI: 10.1016/j.reth.2024.12.004
Lizhen Long , Xiaoan Ma , Hua Zhang , Changgong Lan
In this work, laponite (LAP) was used to develop the silver (Ag) based nanocomposite for improved anti-bacterial action and wound healing properties. The amphiphilic co-polymers such as PLGA polymer was embedded with the surface of LAP molecules and polyethyleneimine (PEI) through the interaction of hydrophobic binding and it was formed as LAP/PLA-PEG/PEI formulation through the coupling chemistry. The Ag nanoparticles was loaded into formulation to develop LAP/PLA-PEG/PEI/Ag nanocomposite and characterized by different analytical techniques. The UV–Vis and XRD results report that the nanocomposite has shown Surface Plasmon Resonance (SPR) peak at 415 nm for AgNPs particles and provide the strong intensity peak along with 48 nm particle size, respectively. The HR-TEM image showed that the LAP/PLA-PEG/PEI/Ag nanocomposite has shown crystal lattice with spherical morphology. In addition, the synthesized nanocomposite requested in the swelling along with degradation, radial scavenging activity and drug releasing behaviour by in vitro method. The anti-bacterial analysis results showed that the nanocomposite have greater bacterial inhibition. Moreover, In vitro cell model and In vivo wound healing studies confirmed that nanocomposite have significant biocompatibility and healing properties. Importantly, in vivo histological analyses confirmed the effective wound healing effect of nanocomposite by complete re-epithelialization, formation of new granulation tissue and blood vessels. These observations provide strong evidences to use this novel nanoformulation for wound healing application with anti-microbial action.
在这项工作中,拉脱土(LAP)被用于开发银(Ag)基纳米复合材料,以提高抗菌作用和伤口愈合性能。将PLGA聚合物等两亲共聚物通过疏水结合相互作用嵌入LAP分子和聚乙烯亚胺(PEI)表面,通过偶联化学反应形成LAP/PLA-PEG/PEI配方。将银纳米粒子加入到配方中制备LAP/PLA-PEG/PEI/Ag纳米复合材料,并采用不同的分析技术对其进行表征。UV-Vis和XRD结果表明,AgNPs颗粒在415 nm处出现了表面等离子体共振峰(SPR),并在48 nm处出现了强强度峰。hrtem图像显示,LAP/PLA-PEG/PEI/Ag纳米复合材料呈球形晶格结构。体外实验结果表明,所合成的纳米复合材料具有良好的溶胀降解能力、径向清除能力和药物释放能力。抗菌分析结果表明,该纳米复合材料具有较好的抑菌效果。此外,体外细胞模型和体内伤口愈合研究证实,纳米复合材料具有显著的生物相容性和愈合性能。重要的是,体内组织学分析证实了纳米复合材料通过完全的再上皮化、新肉芽组织和血管的形成而有效的伤口愈合效果。这些观察结果为使用这种具有抗菌作用的新型纳米制剂用于伤口愈合提供了强有力的证据。
{"title":"Novel preparation of laponite based theranostic silver nanocomposite for drug delivery, radical scavenging and healing efficiency for wound care management after surgery","authors":"Lizhen Long ,&nbsp;Xiaoan Ma ,&nbsp;Hua Zhang ,&nbsp;Changgong Lan","doi":"10.1016/j.reth.2024.12.004","DOIUrl":"10.1016/j.reth.2024.12.004","url":null,"abstract":"<div><div>In this work, laponite (LAP) was used to develop the silver (Ag) based nanocomposite for improved anti-bacterial action and wound healing properties. The amphiphilic co-polymers such as PLGA polymer was embedded with the surface of LAP molecules and polyethyleneimine (PEI) through the interaction of hydrophobic binding and it was formed as LAP/PLA-PEG/PEI formulation through the coupling chemistry. The Ag nanoparticles was loaded into formulation to develop LAP/PLA-PEG/PEI/Ag nanocomposite and characterized by different analytical techniques. The UV–Vis and XRD results report that the nanocomposite has shown Surface Plasmon Resonance (SPR) peak at 415 nm for AgNPs particles and provide the strong intensity peak along with 48 nm particle size, respectively. The HR-TEM image showed that the LAP/PLA-PEG/PEI/Ag nanocomposite has shown crystal lattice with spherical morphology. In addition, the synthesized nanocomposite requested in the swelling along with degradation, radial scavenging activity and drug releasing behaviour by <em>in vitro</em> method. The anti-bacterial analysis results showed that the nanocomposite have greater bacterial inhibition. Moreover, <em>In vitro</em> cell model and <em>In vivo</em> wound healing studies confirmed that nanocomposite have significant biocompatibility and healing properties. Importantly, <em>in vivo</em> histological analyses confirmed the effective wound healing effect of nanocomposite by complete re-epithelialization, formation of new granulation tissue and blood vessels. These observations provide strong evidences to use this novel nanoformulation for wound healing application with anti-microbial action.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"28 ","pages":"Pages 235-245"},"PeriodicalIF":3.4,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11745969/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143010687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Baseline magnetic resonance imaging findings associated with short-term clinical outcomes after intraarticular administration of autologous adipose-derived stem cells for knee osteoarthritis 基线磁共振成像结果与关节内给药自体脂肪来源干细胞治疗膝骨关节炎后的短期临床结果相关。
IF 3.4 3区 环境科学与生态学 Q3 CELL & TISSUE ENGINEERING Pub Date : 2024-12-26 DOI: 10.1016/j.reth.2024.12.012
Ryota Yamagami , Tomohiro Terao , Taro Kasai , Hisatoshi Ishikura , Masaki Hatano , Junya Higuchi , Shuichi Yoshida , Yusuke Arino , Ryo Murakami , Masashi Sato , Yuji Maenohara , Yuma Makii , Tokio Matsuzaki , Keita Inoue , Shinsaku Tsuji , Sakae Tanaka , Taku Saito

Introduction

This study aimed to determine the association between the baseline magnetic resonance imaging (MRI) findings and clinical outcomes after articular injection of adipose-derived mesenchymal stem cells (ASCs) for knee osteoarthritis (KOA).

Methods

This retrospective study included 149 patients with varus-type KOA treated with a single intraarticular ASC injection. All patients underwent a MRI evaluation before treatment. Patients were categorized following the MRI Osteoarthritis Knee Score (MOAKS) system cartilage score into the mild, moderate, or severe KOA groups. Additionally, joint effusion and synovitis, bone marrow lesions (BMLs), and meniscal extrusions were graded with the MOAKS. Knee Osteoarthritis Outcome Score (KOOS) was obtained at baseline, 1-, 3-, 6-, and 12-month posttreatment. The responder rate in the Outcome Measures in Arthritis Clinical Trials-Osteoarthritis Research Society International was assessed with the KOOS. Multivariate logistic regression analyses were conducted to determine factors associated with the responder rate.

Results

All KOOS subscales significantly enhanced with the greatest improvement from baseline to 6 months which plateaued between 6 and 12 months. The responder rate was 65.4 % in the mild/moderate KOA compared to 35.2 % in the severe KOA at 12 months. Lower OA grade (odds ratio [OR]: 0.52; 95 % confidence interval (CI): 0.31–0.88; P = 0.015), smaller BMLs in medial femoral condyle (OR: 0.36; 95 % CI: 0.14–0.94; P = 0.037), and less meniscal extrusion (OR: 0.31; 95 % CI: 0.11–0.89; P = 0.029) were associated with higher responder rate at 6 months in multivariable logistic regression analysis. The factors associated with higher responder rate at 12 months included lower OA grade (OR: 0.42; 95 % CI: 0.25–0.73; P = 0.002) and younger age (OR: 1.04; 95 % CI: 1.00–1.08; P = 0.042).

Conclusions

ASC treatment for KOA enhanced short-term clinical outcomes. MRI findings, including cartilage lesions, BMLs, and meniscal extrusion, were associated with responder rate, helping physicians identify which patients may benefit from this therapy.
本研究旨在确定关节注射脂肪源性间充质干细胞(ASCs)治疗膝骨关节炎(KOA)后的基线磁共振成像(MRI)结果与临床结果之间的关系。方法:采用单次关节内注射ASC治疗内翻型KOA患者149例。所有患者在治疗前都进行了MRI评估。患者按照MRI骨关节炎膝关节评分(MOAKS)系统软骨评分分为轻度、中度和重度KOA组。此外,关节积液和滑膜炎、骨髓病变(BMLs)和半月板突出用MOAKS分级。在基线、治疗后1、3、6和12个月获得膝关节骨性关节炎结局评分(oos)。关节炎临床试验结果测量-国际骨关节炎研究学会的应答率用oos进行评估。进行多变量logistic回归分析以确定与应答率相关的因素。结果:所有oos亚量表均显著增强,从基线到6个月改善最大,6至12个月达到稳定。12个月时,轻/中度KOA的应答率为65.4%,而重度KOA的应答率为35.2%。OA分级较低(优势比[OR]: 0.52;95%置信区间(CI): 0.31-0.88;P = 0.015),股骨内侧髁bml较小(OR: 0.36;95% ci: 0.14-0.94;P = 0.037),半月板挤压较少(OR: 0.31;95% ci: 0.11-0.89;在多变量logistic回归分析中,P = 0.029)与6个月时较高的应答率相关。与12个月应答率较高相关的因素包括OA等级较低(OR: 0.42;95% ci: 0.25-0.73;P = 0.002)和年龄更小(OR: 1.04;95% ci: 1.00-1.08;p = 0.042)。结论:ASC治疗可提高KOA的短期临床疗效。MRI检查结果,包括软骨病变、BMLs和半月板挤压,与应答率相关,帮助医生确定哪些患者可能从这种治疗中受益。
{"title":"Baseline magnetic resonance imaging findings associated with short-term clinical outcomes after intraarticular administration of autologous adipose-derived stem cells for knee osteoarthritis","authors":"Ryota Yamagami ,&nbsp;Tomohiro Terao ,&nbsp;Taro Kasai ,&nbsp;Hisatoshi Ishikura ,&nbsp;Masaki Hatano ,&nbsp;Junya Higuchi ,&nbsp;Shuichi Yoshida ,&nbsp;Yusuke Arino ,&nbsp;Ryo Murakami ,&nbsp;Masashi Sato ,&nbsp;Yuji Maenohara ,&nbsp;Yuma Makii ,&nbsp;Tokio Matsuzaki ,&nbsp;Keita Inoue ,&nbsp;Shinsaku Tsuji ,&nbsp;Sakae Tanaka ,&nbsp;Taku Saito","doi":"10.1016/j.reth.2024.12.012","DOIUrl":"10.1016/j.reth.2024.12.012","url":null,"abstract":"<div><h3>Introduction</h3><div>This study aimed to determine the association between the baseline magnetic resonance imaging (MRI) findings and clinical outcomes after articular injection of adipose-derived mesenchymal stem cells (ASCs) for knee osteoarthritis (KOA).</div></div><div><h3>Methods</h3><div>This retrospective study included 149 patients with varus-type KOA treated with a single intraarticular ASC injection. All patients underwent a MRI evaluation before treatment. Patients were categorized following the MRI Osteoarthritis Knee Score (MOAKS) system cartilage score into the mild, moderate, or severe KOA groups. Additionally, joint effusion and synovitis, bone marrow lesions (BMLs), and meniscal extrusions were graded with the MOAKS. Knee Osteoarthritis Outcome Score (KOOS) was obtained at baseline, 1-, 3-, 6-, and 12-month posttreatment. The responder rate in the Outcome Measures in Arthritis Clinical Trials-Osteoarthritis Research Society International was assessed with the KOOS. Multivariate logistic regression analyses were conducted to determine factors associated with the responder rate.</div></div><div><h3>Results</h3><div>All KOOS subscales significantly enhanced with the greatest improvement from baseline to 6 months which plateaued between 6 and 12 months. The responder rate was 65.4 % in the mild/moderate KOA compared to 35.2 % in the severe KOA at 12 months. Lower OA grade (odds ratio [OR]: 0.52; 95 % confidence interval (CI): 0.31–0.88; <em>P</em> = 0.015), smaller BMLs in medial femoral condyle (OR: 0.36; 95 % CI: 0.14–0.94; <em>P</em> = 0.037), and less meniscal extrusion (OR: 0.31; 95 % CI: 0.11–0.89; <em>P</em> = 0.029) were associated with higher responder rate at 6 months in multivariable logistic regression analysis. The factors associated with higher responder rate at 12 months included lower OA grade (OR: 0.42; 95 % CI: 0.25–0.73; <em>P</em> = 0.002) and younger age (OR: 1.04; 95 % CI: 1.00–1.08; <em>P</em> = 0.042).</div></div><div><h3>Conclusions</h3><div>ASC treatment for KOA enhanced short-term clinical outcomes. MRI findings, including cartilage lesions, BMLs, and meniscal extrusion, were associated with responder rate, helping physicians identify which patients may benefit from this therapy.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"28 ","pages":"Pages 227-234"},"PeriodicalIF":3.4,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11741093/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143010684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The role of GATA4 in mesenchymal stem cell senescence: A new frontier in regenerative medicine GATA4在间充质干细胞衰老中的作用:再生医学的新前沿。
IF 3.4 3区 环境科学与生态学 Q3 CELL & TISSUE ENGINEERING Pub Date : 2024-12-25 DOI: 10.1016/j.reth.2024.11.017
M. Arockia Babu , Renuka Jyothi S , Irwanjot Kaur , Sachin Kumar , Naveen Sharma , M. Ravi Kumar , Pranchal Rajput , Haider Ali , Gaurav Gupta , Vetriselvan Subramaniyan , Ling Shing Wong , Vinoth Kumarasamy
The Mesenchymal Stem Cell (MSC) is a multipotent progenitor cell with known differentiation potential towards various cell lineage, making it an appealing candidate for regenerative medicine. One major contributing factor to age-related MSC dysfunction is cellular senescence, which is the hallmark of relatively irreversible growth arrest and changes in functional properties. GATA4, a zinc-finger transcription factor, emerges as a critical regulator in MSC biology. Originally identified as a key regulator of heart development and specification, GATA4 has since been connected to several aspects of cellular processes, including stem cell proliferation and differentiation. Accumulating evidence suggests that the involvement of GATA4-nuclear signalizing in the process of MSC senescence-related traits may contribute to age-induced alterations in MSC behavior. GATA4 emerged as the central player in MSC senescence, interacting with several signaling pathways. Studies have shown that GATA4 expression is reduced with age in MSCs, which is associated with increased expression levels of senescence markers and impaired regenerative potential. At the mechanistic level, GATA4 regulates the expression of genes involved in cell cycle regulation, DNA repair, and oxidative stress response, thereby influencing the senescence phenotype in MSCs. The findings underscore the critical function of GATA4 in MSC homeostasis and suggest a promising new target to restore stem cell function during aging and disease. A better understanding of the molecular mechanisms that underlie GATA4 mediated modulation of MSC senescence would provide an opportunity to develop new therapies to revitalize old MSCs to increase their regenerative function for therapeutic purposes in regenerative medicine.
间充质干细胞(MSC)是一种多能祖细胞,具有向各种细胞谱系分化的潜力,使其成为再生医学的一个有吸引力的候选者。与年龄相关的间充质干细胞功能障碍的一个主要因素是细胞衰老,这是相对不可逆的生长停滞和功能特性变化的标志。锌指转录因子GATA4是MSC生物学中一个重要的调控因子。GATA4最初被认为是心脏发育和规范的关键调节因子,后来被认为与细胞过程的几个方面有关,包括干细胞增殖和分化。越来越多的证据表明,gata4核信号参与MSC衰老相关性状的过程可能有助于年龄诱导的MSC行为改变。GATA4是MSC衰老的核心参与者,与几种信号通路相互作用。研究表明,MSCs中GATA4的表达随着年龄的增长而降低,这与衰老标志物的表达水平增加和再生潜力受损有关。在机制水平上,GATA4调节参与细胞周期调控、DNA修复和氧化应激反应的基因表达,从而影响MSCs的衰老表型。这些发现强调了GATA4在MSC稳态中的关键功能,并提出了一个有希望的新靶点来恢复衰老和疾病期间的干细胞功能。更好地了解GATA4介导的间充质干细胞衰老的分子机制将为开发新疗法提供机会,以使年老的间充质干细胞恢复活力,从而增加其再生功能,用于再生医学的治疗目的。
{"title":"The role of GATA4 in mesenchymal stem cell senescence: A new frontier in regenerative medicine","authors":"M. Arockia Babu ,&nbsp;Renuka Jyothi S ,&nbsp;Irwanjot Kaur ,&nbsp;Sachin Kumar ,&nbsp;Naveen Sharma ,&nbsp;M. Ravi Kumar ,&nbsp;Pranchal Rajput ,&nbsp;Haider Ali ,&nbsp;Gaurav Gupta ,&nbsp;Vetriselvan Subramaniyan ,&nbsp;Ling Shing Wong ,&nbsp;Vinoth Kumarasamy","doi":"10.1016/j.reth.2024.11.017","DOIUrl":"10.1016/j.reth.2024.11.017","url":null,"abstract":"<div><div>The Mesenchymal Stem Cell (MSC) is a multipotent progenitor cell with known differentiation potential towards various cell lineage, making it an appealing candidate for regenerative medicine. One major contributing factor to age-related MSC dysfunction is cellular senescence, which is the hallmark of relatively irreversible growth arrest and changes in functional properties. GATA4, a zinc-finger transcription factor, emerges as a critical regulator in MSC biology. Originally identified as a key regulator of heart development and specification, GATA4 has since been connected to several aspects of cellular processes, including stem cell proliferation and differentiation. Accumulating evidence suggests that the involvement of GATA4-nuclear signalizing in the process of MSC senescence-related traits may contribute to age-induced alterations in MSC behavior. GATA4 emerged as the central player in MSC senescence, interacting with several signaling pathways. Studies have shown that GATA4 expression is reduced with age in MSCs, which is associated with increased expression levels of senescence markers and impaired regenerative potential. At the mechanistic level, GATA4 regulates the expression of genes involved in cell cycle regulation, DNA repair, and oxidative stress response, thereby influencing the senescence phenotype in MSCs. The findings underscore the critical function of GATA4 in MSC homeostasis and suggest a promising new target to restore stem cell function during aging and disease. A better understanding of the molecular mechanisms that underlie GATA4 mediated modulation of MSC senescence would provide an opportunity to develop new therapies to revitalize old MSCs to increase their regenerative function for therapeutic purposes in regenerative medicine.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"28 ","pages":"Pages 214-226"},"PeriodicalIF":3.4,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11731776/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142984638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
MAPT-A152T mutation drives neuronal hyperactivity through Fyn-NMDAR signaling in human iPSC-Derived neurons: Insights into Alzheimer's pathogenesis MAPT-A152T突变通过人类ipsc衍生神经元中的fn - nmdar信号驱动神经元过度活跃:对阿尔茨海默病发病机制的见解
IF 3.4 3区 环境科学与生态学 Q3 CELL & TISSUE ENGINEERING Pub Date : 2024-12-24 DOI: 10.1016/j.reth.2024.12.009
Maika Itsuno , Hirokazu Tanabe , Etsuko Sano , Takashi Sasaki , Chisato Oyama , Hiroko Bannai , Koichi Saito , Kazuhiko Nakata , Setsu Endoh-Yamagami , Hideyuki Okano , Sumihiro Maeda

Introduction

Tau protein plays a pivotal role in the pathogenesis of Alzheimer's disease (AD) and in regulating neuronal excitability. Among tau-coding microtubule associated protein tau (MAPT) gene mutations, the A152T mutation is reported to increase the risk of AD and neuronal excitability in mouse models.

Methods

To investigate the effects of MAPT gene expression and its mutations on neuronal activity in human neurons, we employed genome editing technology to introduce the A152T or P301S mutations into induced pluripotent stem cells (iPSCs). We then differentiated them into excitatory and inhibitory neurons. As a control, iPSCs in which the MAPT gene was replaced with a fluorescent protein were also created.

Results

In excitatory neuronal cultures, the A152T mutation was found to enhance spontaneous neuronal activity and the association of tau and Fyn. However, in inhibitory neuron-enriched cultures, the A152T mutation did not affect neuronal activity. Inhibition of NMDA receptors (NMDAR) and the reduction of tau protein levels decreased neuronal excitability in both A152T/A152T and healthy control (WT/WT) excitatory neurons. In addition, the A152T mutation increased the interaction between tau and Fyn. These findings suggest that the tau-Fyn interaction plays a critical role in regulating neuronal activity under physiological conditions, while the A152T mutation enhances neuronal activity by strengthening this endogenous interaction between tau and Fyn. In addition, transcriptomic analysis revealed structural changes specific to excitatory neurons with the A152T mutation. Common changes observed in both A152T and P301S lines recapitulated a dedifferentiation phenotype, consistent with previous reports.

Conclusions

These data demonstrate that the A152T mutation in the MAPT gene increases neuronal excitability through the tau-Fyn-NMDAR pathway in excitatory neurons, shedding light on its role in AD pathogenesis.
Tau蛋白在阿尔茨海默病(AD)的发病机制和调节神经元兴奋性中起着关键作用。在tau编码微管相关蛋白tau (MAPT)基因突变中,有报道称A152T突变可增加小鼠模型中AD和神经元兴奋性的风险。方法:为了研究MAPT基因表达及其突变对人类神经元神经元活性的影响,我们采用基因组编辑技术将A152T或P301S突变导入诱导多能干细胞(iPSCs)。然后将其分化为兴奋性神经元和抑制性神经元。作为对照,MAPT基因被荧光蛋白取代的iPSCs也被创造出来。结果:在兴奋性神经元培养中,发现A152T突变增强了自发神经元活动以及tau和Fyn的关联。然而,在抑制性神经元富集培养中,A152T突变不影响神经元活性。NMDA受体(NMDAR)的抑制和tau蛋白水平的降低降低了A152T/A152T和健康对照(WT/WT)兴奋性神经元的兴奋性。此外,A152T突变增加了tau和Fyn之间的相互作用。这些发现表明,在生理条件下,tau-Fyn相互作用在调节神经元活动中起着关键作用,而A152T突变通过加强tau和Fyn之间的内源性相互作用来增强神经元活动。此外,转录组学分析揭示了A152T突变的兴奋性神经元特有的结构变化。在A152T和P301S系中观察到的共同变化再现了去分化表型,与先前的报道一致。结论:这些数据表明,MAPT基因的A152T突变通过兴奋性神经元的tau-Fyn-NMDAR通路增加神经元的兴奋性,揭示了其在AD发病机制中的作用。
{"title":"MAPT-A152T mutation drives neuronal hyperactivity through Fyn-NMDAR signaling in human iPSC-Derived neurons: Insights into Alzheimer's pathogenesis","authors":"Maika Itsuno ,&nbsp;Hirokazu Tanabe ,&nbsp;Etsuko Sano ,&nbsp;Takashi Sasaki ,&nbsp;Chisato Oyama ,&nbsp;Hiroko Bannai ,&nbsp;Koichi Saito ,&nbsp;Kazuhiko Nakata ,&nbsp;Setsu Endoh-Yamagami ,&nbsp;Hideyuki Okano ,&nbsp;Sumihiro Maeda","doi":"10.1016/j.reth.2024.12.009","DOIUrl":"10.1016/j.reth.2024.12.009","url":null,"abstract":"<div><h3>Introduction</h3><div>Tau protein plays a pivotal role in the pathogenesis of Alzheimer's disease (AD) and in regulating neuronal excitability. Among tau-coding microtubule associated protein tau (<em>MAPT</em>) gene mutations, the A152T mutation is reported to increase the risk of AD and neuronal excitability in mouse models.</div></div><div><h3>Methods</h3><div>To investigate the effects of <em>MAPT</em> gene expression and its mutations on neuronal activity in human neurons, we employed genome editing technology to introduce the A152T or P301S mutations into induced pluripotent stem cells (iPSCs). We then differentiated them into excitatory and inhibitory neurons. As a control, iPSCs in which the <em>MAPT</em> gene was replaced with a fluorescent protein were also created.</div></div><div><h3>Results</h3><div>In excitatory neuronal cultures, the A152T mutation was found to enhance spontaneous neuronal activity and the association of tau and Fyn. However, in inhibitory neuron-enriched cultures, the A152T mutation did not affect neuronal activity. Inhibition of NMDA receptors (NMDAR) and the reduction of tau protein levels decreased neuronal excitability in both A152T/A152T and healthy control (WT/WT) excitatory neurons. In addition, the A152T mutation increased the interaction between tau and Fyn. These findings suggest that the tau-Fyn interaction plays a critical role in regulating neuronal activity under physiological conditions, while the A152T mutation enhances neuronal activity by strengthening this endogenous interaction between tau and Fyn. In addition, transcriptomic analysis revealed structural changes specific to excitatory neurons with the A152T mutation. Common changes observed in both A152T and P301S lines recapitulated a dedifferentiation phenotype, consistent with previous reports.</div></div><div><h3>Conclusions</h3><div>These data demonstrate that the A152T mutation in the <em>MAPT</em> gene increases neuronal excitability through the tau-Fyn-NMDAR pathway in excitatory neurons, shedding light on its role in AD pathogenesis.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"28 ","pages":"Pages 201-213"},"PeriodicalIF":3.4,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11730958/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142984635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Stem cell therapy for bladder regeneration: A comprehensive systematic review 干细胞治疗膀胱再生:一项全面的系统综述。
IF 3.4 3区 环境科学与生态学 Q3 CELL & TISSUE ENGINEERING Pub Date : 2024-12-21 DOI: 10.1016/j.reth.2024.12.005
Ali Faegh , Shima Jahani , Fatemeh Chinisaz , Hamoon Baghaei , Masoumeh Majidi Zolbin
Tissue engineering has been considered a potential choice for urinary system reconstruction. Here, we aim to a broad spectrum of employed stem cells in bladder regeneration by performing a comprehensive systematic review. In January 2024, we searched Scopus, PubMed, and Embase databases for studies that tried bladder regeneration by tissue engineering using stem cells. We excluded non-English studies, review articles, and manuscripts that met the other exclusion criteria. Among 43 included studies, comparative studies demonstrated the similar or superior potentiality of stem cells to regenerate tissues and improve bladder function compared with autologous cells. Furthermore, data suggest an increased use of bio-synthetic scaffolds and their appropriate bio-compatibility with stem cells. The evidence establishes that adipose-derived and bone marrow-derived mesenchymal stem cells are the most frequently used stem cells. And both are suitable for urothelium and smooth muscle formation along with the capability of bone marrow-derived mesenchymal stem cells for lamina propria formation. Additionally, the competency of smooth muscle-derived progenitor cells, urine-derived stem cells, umbilical mesenchymal SCs for smooth muscle and urothelium regeneration, and the capability of hair follicle stem cells for smooth muscle formation are demonstrated. Also, the superiority of endothelial progenitor cells for neo-vascularization and smooth muscle progenitor cells for neuron formation are demonstrated. In addition to adding growth factors to the culturing media, hypoxic conditions and intra-peritoneal incubation are introduced as promoter conditions that can improve histological and physiological components. Available evidence is limited, although it suggests the precious capability of stem cells for bladder regeneration.
组织工程一直被认为是泌尿系统重建的潜在选择。在此,我们旨在通过全面的系统综述,广泛了解干细胞在膀胱再生中的应用。2024年1月,我们在Scopus、PubMed和Embase数据库中搜索了尝试利用干细胞组织工程进行膀胱再生的研究。我们排除了非英文研究、综述文章和符合其他排除标准的稿件。在43项纳入的研究中,对比研究表明,干细胞在组织再生和改善膀胱功能方面的潜力与自体细胞相似或更胜一筹。此外,数据还表明,生物合成支架的使用越来越多,它们与干细胞具有适当的生物兼容性。有证据表明,脂肪间充质干细胞和骨髓间充质干细胞是最常用的干细胞。这两种干细胞都适合尿路上皮细胞和平滑肌的形成,骨髓间充质干细胞还能形成固有膜。此外,平滑肌来源的祖细胞、尿来源的干细胞、脐带间充质干细胞对平滑肌和尿路上皮再生的能力,以及毛囊干细胞对平滑肌形成的能力也得到了证明。此外,还证明了内皮祖细胞和平滑肌祖细胞在血管新生和神经元形成方面的优越性。除了在培养基中添加生长因子外,还引入了缺氧条件和腹膜内培养,作为可改善组织学和生理学成分的促进条件。虽然现有证据有限,但这表明干细胞具有宝贵的膀胱再生能力。
{"title":"Stem cell therapy for bladder regeneration: A comprehensive systematic review","authors":"Ali Faegh ,&nbsp;Shima Jahani ,&nbsp;Fatemeh Chinisaz ,&nbsp;Hamoon Baghaei ,&nbsp;Masoumeh Majidi Zolbin","doi":"10.1016/j.reth.2024.12.005","DOIUrl":"10.1016/j.reth.2024.12.005","url":null,"abstract":"<div><div>Tissue engineering has been considered a potential choice for urinary system reconstruction. Here, we aim to a broad spectrum of employed stem cells in bladder regeneration by performing a comprehensive systematic review. In January 2024, we searched Scopus, PubMed, and Embase databases for studies that tried bladder regeneration by tissue engineering using stem cells. We excluded non-English studies, review articles, and manuscripts that met the other exclusion criteria. Among 43 included studies, comparative studies demonstrated the similar or superior potentiality of stem cells to regenerate tissues and improve bladder function compared with autologous cells. Furthermore, data suggest an increased use of bio-synthetic scaffolds and their appropriate bio-compatibility with stem cells. The evidence establishes that adipose-derived and bone marrow-derived mesenchymal stem cells are the most frequently used stem cells. And both are suitable for urothelium and smooth muscle formation along with the capability of bone marrow-derived mesenchymal stem cells for lamina propria formation. Additionally, the competency of smooth muscle-derived progenitor cells, urine-derived stem cells, umbilical mesenchymal SCs for smooth muscle and urothelium regeneration, and the capability of hair follicle stem cells for smooth muscle formation are demonstrated. Also, the superiority of endothelial progenitor cells for neo-vascularization and smooth muscle progenitor cells for neuron formation are demonstrated. In addition to adding growth factors to the culturing media, hypoxic conditions and intra-peritoneal incubation are introduced as promoter conditions that can improve histological and physiological components. Available evidence is limited, although it suggests the precious capability of stem cells for bladder regeneration.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"28 ","pages":"Pages 191-200"},"PeriodicalIF":3.4,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11729686/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142984637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Standardizing decellularization protocols for optimized uterine tissue bioengineering 优化子宫组织生物工程的标准化脱细胞方案。
IF 3.4 3区 环境科学与生态学 Q3 CELL & TISSUE ENGINEERING Pub Date : 2024-12-21 DOI: 10.1016/j.reth.2024.12.011
Edina Sehic , Lucía de Miguel-Gómez
Bioengineering is applied in different areas, including women's infertility management. Among other approaches, decellularized tissues are being used to treat uterine disorders causing infertility. Biomaterials made from decellularized tissue consist of tissue-specific extracellular matrix and, as acellular scaffolds, are thought to be immune inert. Hence, they are good grafting candidates to replace and regenerate excised damaged uterine tissue to cure infertility. However, decellularization approaches differ among species and research groups, posing challenges for comparison and standardization. The diversity in data reporting and studied properties of the resulting decellularized scaffold make it even more difficult, especially when the ultimate goal is clinical translation. Thus, this review aims to critically assess whole uterus decellularization studies, extracting and comparing their main results and conclusions. After carefully evaluating the reviewed studies, we noticed that the vast majority base the uterus decellularization success and resulting scaffold efficacy on the DNA removal efficacy, while other crucial aspects, including the extracellular matrix integrity or immunogenicity, are underestimated. Thus, this review further proposes practical points for what should be considered and how results can be reported in studies involving whole uterus decellularization to facilitate comparison between studies and translational progress.
生物工程应用于不同的领域,包括妇女不孕症的管理。在其他方法中,脱细胞组织被用于治疗引起不孕症的子宫疾病。由脱细胞组织制成的生物材料由组织特异性细胞外基质组成,作为脱细胞支架,被认为是免疫惰性的。因此,它们是替代和再生切除受损子宫组织以治疗不孕症的良好移植候选者。然而,不同物种和研究小组的脱细胞方法不同,这对比较和标准化提出了挑战。数据报告的多样性和所研究的脱细胞支架的特性使其更加困难,特别是当最终目标是临床翻译时。因此,本综述旨在批判性地评价全子宫脱细胞研究,提取并比较其主要结果和结论。在仔细评估了所回顾的研究后,我们注意到绝大多数基于子宫脱细胞成功和由此产生的支架效果的DNA去除效果,而其他关键方面,包括细胞外基质完整性或免疫原性,被低估了。因此,这篇综述进一步提出了在全子宫脱细胞的研究中应该考虑什么以及如何报告结果的实用要点,以便于研究和转化进展之间的比较。
{"title":"Standardizing decellularization protocols for optimized uterine tissue bioengineering","authors":"Edina Sehic ,&nbsp;Lucía de Miguel-Gómez","doi":"10.1016/j.reth.2024.12.011","DOIUrl":"10.1016/j.reth.2024.12.011","url":null,"abstract":"<div><div>Bioengineering is applied in different areas, including women's infertility management. Among other approaches, decellularized tissues are being used to treat uterine disorders causing infertility. Biomaterials made from decellularized tissue consist of tissue-specific extracellular matrix and, as acellular scaffolds, are thought to be immune inert. Hence, they are good grafting candidates to replace and regenerate excised damaged uterine tissue to cure infertility. However, decellularization approaches differ among species and research groups, posing challenges for comparison and standardization. The diversity in data reporting and studied properties of the resulting decellularized scaffold make it even more difficult, especially when the ultimate goal is clinical translation. Thus, this review aims to critically assess whole uterus decellularization studies, extracting and comparing their main results and conclusions. After carefully evaluating the reviewed studies, we noticed that the vast majority base the uterus decellularization success and resulting scaffold efficacy on the DNA removal efficacy, while other crucial aspects, including the extracellular matrix integrity or immunogenicity, are underestimated. Thus, this review further proposes practical points for what should be considered and how results can be reported in studies involving whole uterus decellularization to facilitate comparison between studies and translational progress.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"28 ","pages":"Pages 183-190"},"PeriodicalIF":3.4,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11731971/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142984636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","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
Regenerative Therapy
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