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Construction of a Cancer Stem Cell related Histone Acetylation Regulatory Genes Prognostic Model for Hepatocellular Carcinoma via Bioinformatics Analysis: Implications for Tumor Chemotherapy and Immunity. 通过生物信息学分析构建与癌症干细胞相关的肝细胞癌组蛋白乙酰化调控基因预后模型:肿瘤化疗和免疫的意义
Pub Date : 2024-03-28 DOI: 10.2174/011574888X305642240327041753
Qian Dai, Jie Zhu, Jing Yang, Chun-Yan Zhang, Wen-Jing Yang, Bai-Shen Pan, Xin-Rong Yang, Wei Guo, Bei-Li Wang

Background: Cancer stem cells (CSC) play an important role in the development of Liver Hepatocellular Carcinoma (LIHC). However, the regulatory mechanisms between acetylation- associated genes (HAGs) and liver cancer stem cells remain unclear.

Objective: To identify a set of histone acetylation genes (HAGs) with close associations to liver cancer stem cells (LCSCs), and to construct a prognostic model that facilitates more accurate prognosis assessments for LIHC patients.

Methods: LIHC expression data were downloaded from the public databases. Using mRNA expression- based stemness indices (mRNAsi) inferred by One-Class Logistic Regression (OCLR), Differentially Expressed Genes (DEGs) (mRNAsi-High VS. mRNAsi-Low groups) were intersected with DEGs (LIHC VS. normal samples), as well as histone acetylation-associated genes (HAGs), to obtain mRNAsi-HAGs. A risk model was constructed employing the prognostic genes, which were acquired through univariate Cox and Least Shrinkage and Selection Operator (LASSO) regression analyses. Subsequently, independent prognostic factors were identified via univariate and multivariate Cox regression analyses and then a nomogram for prediction of LIHC survival was developed. Additionally, immune infiltration and drug sensitivity analysis were performed to explore the relationships between prognostic genes and immune cells. Finally, the expressions of selected mRNAsi-HAGs were validated in the LIHC tumor sphere by quantitative Reverse Transcription Polymerase Chain Reaction (qRT-PCR) assay and western blot analysis.

Results: Among 13 identified mRNAsi-HAGs, 3 prognostic genes (HDAC1, HDAC11, and HAT1) were selected to construct a risk model (mRNAsi-HAGs risk score = 0.02 * HDAC1 + 0.09 * HAT1 + 0.05 * HDAC11). T-stage, mRNAsi, and mRNAsi-HAGs risk scores were identified as independent prognostic factors to construct the nomogram, which was proved to predict the survival probability of LIHC patients effectively. We subsequently observed strongly positive correlations between mRNAsi-HAGs risk score and tumor-infiltrating T cells, B cells and macrophages/monocytes. Moreover, we found 8 drugs (Mitomycin C, IPA 3, FTI 277, Bleomycin, Tipifarnib, GSK 650394, AICAR and EHT 1864) had significant correlations with mRNAsi-HAGs risk scores. The expression of HDAC1 and HDAC11 was higher in CSC-like cells in the tumor sphere.

Conclusion: This study constructed a mRNAsi and HAGs-related prognostic model, which has implications for potential immunotherapy and drug treatment of LIHC.

背景:癌症干细胞(CSC)在肝细胞癌(LIHC)的发展过程中发挥着重要作用。然而,乙酰化相关基因(HAGs)与肝癌干细胞之间的调控机制仍不清楚:鉴定一组与肝癌干细胞(LCSCs)密切相关的组蛋白乙酰化基因(HAGs),并构建一个预后模型,以便对LIHC患者进行更准确的预后评估:方法:从公共数据库下载LIHC表达数据。利用单类逻辑回归(OCLR)推断出的基于mRNA表达的干性指数(mRNAsi),将差异表达基因(DEGs)(mRNAsi-高组与mRNAsi-低组)与DEGs(LIHC与正常样本)以及组蛋白乙酰化相关基因(HAGs)相交,得到mRNAsi-HAGs。通过单变量 Cox 和最小收缩和选择操作器(LASSO)回归分析获得的预后基因被用于构建风险模型。随后,通过单变量和多变量 Cox 回归分析确定了独立的预后因素,并绘制了用于预测 LIHC 存活率的提名图。此外,还进行了免疫浸润和药物敏感性分析,以探讨预后基因与免疫细胞之间的关系。最后,通过定量逆转录聚合酶链反应(qRT-PCR)检测和免疫印迹分析验证了所选mRNAsi-HAGs在LIHC肿瘤球中的表达:结果:在13个已鉴定的mRNAsi-HAGs中,选择了3个预后基因(HDAC1、HDAC11和HAT1)构建风险模型(mRNAsi-HAGs风险评分=0.02 * HDAC1 + 0.09 * HAT1 + 0.05 * HDAC11)。T分期、mRNAsi和mRNAsi-HAGs风险评分被确定为独立的预后因素,从而构建了提名图,该提名图被证明能有效预测LIHC患者的生存概率。我们随后观察到,mRNAsi-HAGs 风险评分与肿瘤浸润 T 细胞、B 细胞和巨噬细胞/单核细胞之间呈强正相关。此外,我们还发现 8 种药物(丝裂霉素 C、IPA 3、FTI 277、博莱霉素、Tipifarnib、GSK 650394、AICAR 和 EHT 1864)与 mRNAsi-HAGs 风险评分有显著相关性。在肿瘤球内的CSC样细胞中,HDAC1和HDAC11的表达量较高:本研究构建了一个与mRNAsi和HAGs相关的预后模型,这对LIHC潜在的免疫疗法和药物治疗具有重要意义。
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引用次数: 0
Comparative Outcomes of Intravenous, Intranasal, and Intracerebroventricular Transplantation of Human Neural Stem Cells in Mice Model of Ischemic Stroke. 缺血性脑卒中小鼠模型中人神经干细胞静脉内、鼻内和脑室内移植的疗效比较。
Pub Date : 2024-03-25 DOI: 10.2174/011574888X290104240320041613
Mengze Zhang, Yaying Song, Chong Xie, Yangtai Guan

Background: Transplantation of neural stem cells improves ischemic stroke outcomes in rodent models and is currently in the clinical test stage. However, the optimal delivery route to achieve improved efficacy remains undetermined.

Objective: This study aims to evaluate three more clinically feasible delivery routes: intravenous (IV), intranasal (IN), and intracerebroventricular (ICV). We compared the therapeutic efficacies of the three routes of transplanting human neural stem cells (hNSCs) into mice with permanent middle cerebral artery obstruction (pMCAO).

Methods: Behavioral tests and cresyl violet staining were used to evaluate the therapeutic efficacies of functional recovery and lesion volumes. The expression of proinflammatory cytokines and neurotrophic factors was measured by real-time PCR. The distribution and differentiation of hNSCs were determined by immunofluorescence staining. The effect on endogenous neurogenesis and astrocyte function were determined by immunofluorescence staining and western blot.

Results: hNSC transplantation using the three routes improved behavioral outcomes and reduced lesion volumes; IV transplantation of hNSCs results in earlier efficacy and improves the inflammatory microenvironment. The long-term distribution and differentiation of transplanted hNSCs in the peri-infarct areas can only be evaluated using ICV delivery. IV and ICV transplantation of hNSCs promote neurogenesis and modulate the dual function of astrocytes in the peri-infarct areas.

Conclusion: IV and IN delivery is suitable for repeated administration of hNSCs to achieve improved prognosis. Comparatively, ICV transplantation provides long-term efficacy at lower doses and fewer administration times.

背景:移植神经干细胞可改善啮齿类动物模型的缺血性中风预后,目前正处于临床试验阶段。然而,提高疗效的最佳给药途径仍未确定:本研究旨在评估三种临床可行的给药途径:静脉注射(IV)、鼻内注射(IN)和脑室内注射(ICV)。我们比较了将人神经干细胞(hNSCs)移植到永久性大脑中动脉阻塞(pMCAO)小鼠体内的三种途径的治疗效果:方法:采用行为测试和甲酚紫染色法评估小鼠功能恢复和病变体积的疗效。实时 PCR 检测促炎细胞因子和神经营养因子的表达。免疫荧光染色测定了 hNSCs 的分布和分化。结果:三种途径移植的 hNSCs 均能改善行为结果并减少病变体积;静脉移植的 hNSCs 能更早起效并改善炎症微环境。只有使用ICV给药才能评估移植的hNSCs在梗死周围区域的长期分布和分化情况。IV和ICV移植hNSCs可促进神经发生,并调节梗死周围区域星形胶质细胞的双重功能:结论:静脉注射和静脉输注适用于重复施用 hNSCs,以改善预后。结论:静脉注射和 IN 给药适用于重复给药 hNSCs 以改善预后,而 ICV 移植以较低的剂量和较少的给药时间获得长期疗效。
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引用次数: 0
Bone Marrow-derived Mesenchymal Stem Cell Therapy in Retinitis Pigmentosa. 骨髓间充质干细胞疗法治疗视网膜色素变性。
Pub Date : 2024-03-19 DOI: 10.2174/011574888X293265240311120103
Nil Irem Ucgun, Cenk Zeki Fikret, Mualla Sahin Hamurcu

Background: To determine the effectiveness of bone marrow-derived mesenchymal stem cell therapy on visual acuity and visual field in patients with retinitis pigmentosa.

Objective: Stem cell treatment in retinitis pigmentosa provides improvement in visual acuity and visual field.

Method: Forty-seven eyes of 27 patients diagnosed with retinitis pigmentosa were included in our study. Allogeneic bone marrow-derived mesenchymal stem cells were administered by deep subtenon injection. Complete routine ophthalmological examinations, optical coherence tomography (Zeiss, Cirrus HD-OCT) measurements, and visual field (Humphrey perimetry, 30-2) tests were performed on all patients before the treatment and on the 1st, 3rd, and 6th month after treatment. The best corrected visual acuities of the patients were determined by the Snellen chart and converted to logMAR. Visual evoked potential (VEP) and electroretinogram (ERG) examinations of the patients before the treatment and on the 6th month after the treatment were performed (Metrovision) data were compared.

Results: Visual acuities were 0.74 ± 0.49 logMAR before treatment and 0.61 ± 0.46 logMAR after treatment. Visual acuity had a statistically significant increase (p < 0.001). The visual field deviation was found to be -27.16 ± 5.77 dB before treatment and -26.59 ± 5.96 dB after treatment (p = 0.005). The ganglion cell layer was 46.26 ± 12.87 μm before treatment and 52.47 ± 12.26 μm after treatment (p = 0.003). There was a significant improvement in Pattern VEP 120º P100 amplitude compared to that before the treatment (4.43 ± 2.42 μV) and that after the treatment (5.09 ± 2.86 μV) (p = 0.013). ERG latency measurements were 18.33 ± 15.39 μV before treatment and 20.87 ± 18.64 μV after treatment for scotopic 0.01 (p = 0.02). ERG latency measurements for scotopic 3.0 were 20.75 ± 26.31 μV before treatment and 23.10 ± 28.60 μV after treatment (p = 0.014).

Conclusion: Retinitis pigmentosa is a progressive, inherited disease that can result in severe vision loss. In retinitis pigmentosa, the application of bone marrow-derived mesenchymal stem cells by deep subtenon injection has positive effects on visual function. No systemic or ophthalmic side effects were detected in the patients during the 6-month follow-up period.

背景:研究骨髓间充质干细胞疗法对视网膜色素变性患者视力和视野的影响:目的:确定骨髓间充质干细胞疗法对视网膜色素变性患者视力和视野的影响:干细胞治疗视网膜色素变性可改善视力和视野:我们的研究纳入了27名视网膜色素变性患者的47只眼睛。异体骨髓间充质干细胞通过腱膜下深部注射给药。在治疗前、治疗后第1、3和6个月,对所有患者进行了全面的常规眼科检查、光学相干断层扫描(蔡司,Cirrus HD-OCT)测量和视野(汉弗莱视力计,30-2)测试。患者的最佳矫正视力由斯奈伦视力表确定,并转换为对数分辨力。对治疗前和治疗后第 6 个月的患者进行视觉诱发电位(VEP)和视网膜电图(ERG)检查(Metrovision),并对数据进行比较:治疗前的视力为 0.74 ± 0.49 logMAR,治疗后为 0.61 ± 0.46 logMAR。在统计学上,视力有显著提高(p < 0.001)。治疗前的视野偏差为 -27.16 ± 5.77 dB,治疗后为 -26.59 ± 5.96 dB(p = 0.005)。神经节细胞层在治疗前为 46.26 ± 12.87 μm,治疗后为 52.47 ± 12.26 μm(p = 0.003)。与治疗前(4.43 ± 2.42 μV)和治疗后(5.09 ± 2.86 μV)相比,模式 VEP 120º P100 波幅有明显改善(p = 0.013)。治疗前的ERG潜伏期测量值为18.33 ± 15.39 μV,治疗后的ERG潜伏期测量值为20.87 ± 18.64 μV(散光0.01)(p = 0.02)。散光 3.0 的 ERG 潜伏期测量结果为:治疗前 20.75 ± 26.31 μV,治疗后 23.10 ± 28.60 μV(p = 0.014):视网膜色素变性是一种渐进性遗传疾病,可导致严重的视力丧失。结论:视网膜色素变性症是一种渐进性遗传疾病,可导致严重的视力丧失。在视网膜色素变性症中,通过腱膜下深部注射骨髓间充质干细胞对视功能有积极影响。在6个月的随访期间,未发现患者出现全身或眼部副作用。
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引用次数: 0
Conditioned Medium Treatment for the Improvement of Functional Recovery after Spinal Cord Injury: A Meta-Analysis Study. 改善脊髓损伤后功能恢复的条件介质治疗:一项元分析研究。
Pub Date : 2024-02-28 DOI: 10.2174/011574888X283713240129095031
Razieh Hajisoltani, Mona Taghizadeh, Michael R Hamblin, Fatemeh Ramezani

Background: While there is no certain treatment for spinal cord injury (SCI), stem cellbased therapy may be an attractive alternative, but the survival and differentiation of cells in the host tissue are poor. Conditioned medium (CM) has several beneficial effects on cells.

Objective: In this meta-analysis study, we examined the effect of CM on SCI treatment.

Methods: After searching on MEDLINE, SCOPUS, EMBASE, and Web of Science, first and secondary screening were performed based on title, abstract, and full text. The data were extracted from the included studies, and meta-analysis was performed using STATA.14 software. A standardized mean difference (SMD) with a 95% confidence interval was used to report findings. Quality control and subgroup analysis were also performed.

Results: The results from 52 articles and 61 separate experiments showed that CM had a significantly strong effect on improving motor function after SCI (SMD = 2.58; 95% CI: 2.17 to 2.98; p < 0.001) and also analysis of data from 12 articles demonstrated that CM reduced the expression of GFAP marker (SMD = -4.16; p < 0.0001) compared to SCI group without any treatment. Subgroup analysis showed that treatment with CM of neural stem cells was better than CM of mesenchymal stem cells. It was more effective after a mild lesion than a moderate or severe one. The improvement was more pronounced with <4 weeks than >4 weeks follow-up.

Conclusion: CM had a significant effect in improving motor function after SCI, especially in cases of mild lesions. It has been observed that if CM originates from the neural stem cells, it has a more significant effect than mesenchymal cells.

背景:虽然脊髓损伤(SCI)尚无确定的治疗方法,但基于干细胞的疗法可能是一种有吸引力的替代疗法,但细胞在宿主组织中的存活率和分化率很低。条件培养基(CM)对细胞有多种有益作用:在这项荟萃分析研究中,我们考察了 CM 对 SCI 治疗的影响:方法:在 MEDLINE、SCOPUS、EMBASE 和 Web of Science 上检索后,根据标题、摘要和全文进行初筛和复筛。从纳入的研究中提取数据,并使用 STATA.14 软件进行荟萃分析。报告结果时使用了标准化平均差(SMD)和 95% 置信区间。此外,还进行了质量控制和亚组分析:来自 52 篇文章和 61 个独立实验的结果表明,CM 对改善 SCI 后的运动功能有显著的强效作用(SMD = 2.58;95% CI:2.17 至 2.98;p < 0.001),同时对 12 篇文章的数据进行的分析表明,与未接受任何治疗的 SCI 组相比,CM 可减少 GFAP 标记的表达(SMD = -4.16;p < 0.0001)。分组分析显示,神经干细胞CM治疗效果优于间充质干细胞CM。轻度病变比中度或重度病变更有效。结论:结论:CM对改善脊髓损伤后的运动功能有明显效果,尤其是对轻度损伤的病例。据观察,如果CM源自神经干细胞,其效果比间充质细胞更显著。
{"title":"Conditioned Medium Treatment for the Improvement of Functional Recovery after Spinal Cord Injury: A Meta-Analysis Study.","authors":"Razieh Hajisoltani, Mona Taghizadeh, Michael R Hamblin, Fatemeh Ramezani","doi":"10.2174/011574888X283713240129095031","DOIUrl":"https://doi.org/10.2174/011574888X283713240129095031","url":null,"abstract":"<p><strong>Background: </strong>While there is no certain treatment for spinal cord injury (SCI), stem cellbased therapy may be an attractive alternative, but the survival and differentiation of cells in the host tissue are poor. Conditioned medium (CM) has several beneficial effects on cells.</p><p><strong>Objective: </strong>In this meta-analysis study, we examined the effect of CM on SCI treatment.</p><p><strong>Methods: </strong>After searching on MEDLINE, SCOPUS, EMBASE, and Web of Science, first and secondary screening were performed based on title, abstract, and full text. The data were extracted from the included studies, and meta-analysis was performed using STATA.14 software. A standardized mean difference (SMD) with a 95% confidence interval was used to report findings. Quality control and subgroup analysis were also performed.</p><p><strong>Results: </strong>The results from 52 articles and 61 separate experiments showed that CM had a significantly strong effect on improving motor function after SCI (SMD = 2.58; 95% CI: 2.17 to 2.98; p < 0.001) and also analysis of data from 12 articles demonstrated that CM reduced the expression of GFAP marker (SMD = -4.16; p < 0.0001) compared to SCI group without any treatment. Subgroup analysis showed that treatment with CM of neural stem cells was better than CM of mesenchymal stem cells. It was more effective after a mild lesion than a moderate or severe one. The improvement was more pronounced with <4 weeks than >4 weeks follow-up.</p><p><strong>Conclusion: </strong>CM had a significant effect in improving motor function after SCI, especially in cases of mild lesions. It has been observed that if CM originates from the neural stem cells, it has a more significant effect than mesenchymal cells.</p>","PeriodicalId":93971,"journal":{"name":"Current stem cell research & therapy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139998681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Efficacy and Mechanism of Highly Active Umbilical Cord Mesenchymal Stem Cells in the Treatment of Osteoporosis in Rats. 高活性脐带间充质干细胞治疗大鼠骨质疏松症的功效和机制
Pub Date : 2024-02-14 DOI: 10.2174/011574888X284911240131100909
Chuan Tian, Guanke Lv, Li Ye, Xiaojuan Zhao, Mengdie Chen, Qianqian Ye, Qiang Li, Jing Zhao, Xiangqing Zhu, Xinghua Pan

Background: Osteoporosis increases bone brittleness and the risk of fracture. Umbilical cord mesenchymal stem cell (UCMSC) treatment is effective, but how to improve the biological activity and clinical efficacy of UCMSCs has not been determined.

Methods: A rat model of osteoporosis was induced with dexamethasone sodium phosphate. Highly active umbilical cord mesenchymal stem cells (HA-UCMSCs) and UCMSCs were isolated, cultured, identified, and infused intravenously once at a dose of 2.29 × 106 cells/kg. In the 4th week of treatment, bone mineral density (BMD) was evaluated via cross-micro-CT, tibial structure was observed via HE staining, osteogenic differentiation of bone marrow mesenchymal stem cells (BMMSCs) was examined via alizarin red staining, and carboxy-terminal cross-linked telopeptide (CTX), nuclear factor-κβ ligand (RANKL), procollagen type 1 N-terminal propeptide (PINP) and osteoprotegerin (OPG) levels were investigated via enzyme-linked immunosorbent assays (ELISAs). BMMSCs were treated with 10-6 mol/L dexamethasone and cocultured with HA-UCMSCs and UCMSCs in transwells. The osteogenic and adipogenic differentiation of BMMSCs was subsequently examined through directional induction culture. The protein expression levels of WNT, β-catenin, RUNX2, IFN-γ and IL-17 in the bone tissue were measured via Western blotting.

Results: The BMD in the healthy group was higher than that in the model group. Both UCMSCs and HA-UCMSCs exhibited a fusiform morphology; swirling growth; high expression of CD73, CD90 and CD105; and low expression of CD34 and CD45 and could differentiate into adipocytes, osteoblasts and chondrocytes, while HA-UCMSCs were smaller in size; had a higher nuclear percentage; and higher differentiation efficiency. Compared with those in the model group, the BMD increased, the bone structure improved, the trabecular area, number, and perimeter increased, the osteogenic differentiation of BMMSCs increased, RANKL expression decreased, and PINP expression increased after UCMSC and HA-UCMSC treatment for 4 weeks. Furthermore, the BMD, trabecular area, number and perimeter, calcareous nodule counts, and OPG/RANKL ratio were higher in the HA-UCMSC treatment group than in the UCMSC treatment group. The osteogenic and adipogenic differentiation of dexamethasone-treated BMMSCs was enhanced after the coculture of UCMSCs and HA-UCMSCs, and the HA-UCMSC group exhibited better effects than the UCMSC coculture group. The protein expression of WNT, β-catenin, and runx2 was upregulated, and IFN-γ and IL-17 expression was downregulated after UCMSC and HA-UCMSC treatment.

Conclusion: HA-UCMSCs have a stronger therapeutic effect on osteoporosis compared with that of UCMSCs. These effects include an improved bone structure, increased BMD, an increased number and perimeter of trabeculae, and enhanced osteogenic differentiation of BMMSCs via activation of the WNT/β-catenin

背景:骨质疏松症会增加骨脆性和骨折风险。脐带间充质干细胞(UCMSC)治疗有效,但如何提高 UCMSCs 的生物活性和临床疗效尚未确定:方法:用地塞米松磷酸钠诱导大鼠骨质疏松症模型。分离、培养、鉴定高活性脐带间充质干细胞(HA-UCMSCs)和 UCMSCs,并以 2.29 × 106 cells/kg 的剂量静脉注射一次。在治疗的第四周,通过交叉显微 CT 评估骨矿物质密度(BMD),通过 HE 染色观察胫骨结构,通过茜素红染色检测骨髓间充质干细胞(BMMSCs)的成骨分化、并通过酶联免疫吸附试验(ELISA)检测羧基末端交联端肽(CTX)、核因子κβ配体(RANKL)、1 型胶原 N-末端前肽(PINP)和骨蛋白激酶(OPG)的水平。用 10-6 mol/L 地塞米松处理 BMMSCs,并将其与 HA-UCMSCs 和 UCMSCs 共同培养在转孔中。随后通过定向诱导培养检测了 BMMSCs 的成骨和成脂分化情况。通过 Western 印迹法测定骨组织中 WNT、β-catenin、RUNX2、IFN-γ 和 IL-17 的蛋白表达水平:结果:健康组的 BMD 高于模型组。UCMSCs和HA-UCMSCs均呈纺锤形形态,漩涡状生长,CD73、CD90和CD105高表达,CD34和CD45低表达,可分化为脂肪细胞、成骨细胞和软骨细胞,而HA-UCMSCs体积更小,核比例更高,分化效率更高。与模型组相比,UCMSC 和 HA-UCMSC 治疗 4 周后,BMD 增加,骨结构改善,骨小梁面积、数量和周长增加,BMMSCs 成骨分化增加,RANKL 表达减少,PINP 表达增加。此外,HA-UCMSC 治疗组的 BMD、骨小梁面积、数量和周长、钙化结节计数和 OPG/RANKL 比值均高于 UCMSC 治疗组。UCMSCs与HA-UCMSCs共培养后,地塞米松处理的BMMSCs的成骨和成脂分化能力增强,HA-UCMSC组的效果优于UCMSC共培养组。UCMSC和HA-UCMSC处理后,WNT、β-catenin和runx2蛋白表达上调,IFN-γ和IL-17表达下调:结论:与 UCMSCs 相比,HA-UCMSCs 对骨质疏松症有更强的治疗作用。结论:与 UCMSCs 相比,HA-UCMSCs 对骨质疏松症有更强的治疗作用,这些作用包括改善骨结构、增加 BMD、增加骨小梁的数量和周长,以及通过激活 WNT/β-catenin 通路和抑制炎症增强 BMMSCs 的成骨分化。
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引用次数: 0
Assessing the Impact of Stem Cell-based Therapy on Periodontal Health: A Meta-analysis of Clinical Studies. 评估干细胞疗法对牙周健康的影响:临床研究的元分析。
Pub Date : 2024-02-12 DOI: 10.2174/011574888X294900240130095058
Yu-Han Shao, Yi Song, Qiao-Li Feng, Yan Deng, Tao Tang

Objective: While clinical trials exploring stem cells for regenerating periodontal tissues have demonstrated positive results, there is a limited availability of systematic literature reviews on this subject. To gain a more comprehensive understanding of stem cell interventions in periodontal regeneration, this meta-analysis is undertaken to assess the beneficial effects of stem cells in human periodontal regeneration.

Methods: "PubMed," "Cochrane Library," "Web of Science," "Embase," "Wanfang," and "CNKI," were used to extract clinical studies related to the utilization of stem cells in repairing periodontal tissue defects. This search included studies published up until October 5, 2023. The inclusion criteria required the studies to compare the efficacy of stem cell-based therapy with stem cell-free therapy for regenerating periodontal tissues. Meta-analysis was conducted using Review Manager software (version 5.4).

Results: This meta-analysis synthesized findings from 15 selected studies investigating the impact of stem cell interventions on periodontal tissue regeneration. The "stem cell" group displayed a substantial reduction in clinical attachment level (CAL) compared to the "control" group within 3 to 12 months post-surgery. However, no significant differences in CAL gain were found between groups. Probing pocket depth (PPD) significantly decreased in the "stem cell" group compared to the "control" group, particularly for follow-up periods exceeding 6 months, and dental stem cell treatment exhibited notable improvements. Conversely, no significant differences were observed in PPD reduction. Gingival recession (GR) significantly decreased in the "stem cell" group compared to the "control" group at 3 to 12 months post-surgery. No significant differences were observed in GR reduction between groups. No significant differences were identified in cementoenamel junction-bone distance reduction, infrabony defect reduction, or bone mineral density increase between the two groups. Furthermore, no significant changes were observed in the gingival index, plaque index, or width of keratinized gingiva.

Conclusion: In conclusion, while stem cell-based therapy offers promising prospects for periodontal defect treatment, there are notable limitations in the current body of research. Larger, multicenter, double-blind RCTs with robust methodologies are needed to provide more reliable evidence for stem cell-based intervention in periodontitis.

目的:虽然探索干细胞再生牙周组织的临床试验已取得积极成果,但有关这一主题的系统文献综述却十分有限。为了更全面地了解干细胞对牙周再生的干预,本荟萃分析旨在评估干细胞对人类牙周再生的有益影响:方法:使用 "PubMed"、"Cochrane Library"、"Web of Science"、"Embase"、"Wanfang "和 "CNKI "来提取与利用干细胞修复牙周组织缺损相关的临床研究。该搜索包括截至2023年10月5日发表的研究。纳入标准要求研究比较基于干细胞的疗法和不含干细胞的疗法对牙周组织再生的疗效。使用Review Manager软件(5.4版)进行荟萃分析:这项荟萃分析综合了15项选定研究的结果,这些研究调查了干细胞干预对牙周组织再生的影响。与 "对照 "组相比,"干细胞 "组在术后3至12个月内临床附着水平(CAL)大幅下降。不过,各组之间在CAL增加方面没有发现明显差异。与 "对照 "组相比,"干细胞 "组的探囊深度(PPD)明显下降,特别是在超过6个月的随访期间,牙科干细胞治疗有明显改善。相反,在 PPD 的减少方面没有观察到明显差异。与 "对照 "组相比,"干细胞 "组的牙龈退缩(GR)在术后3至12个月明显减少。各组之间在牙龈退缩方面无明显差异。两组在骨水泥釉交界处-骨距离减少、骨下缺损减少或骨矿物质密度增加方面没有发现明显差异。此外,在牙龈指数、牙菌斑指数或角化牙龈宽度方面也未观察到明显变化:总之,虽然干细胞疗法为牙周缺陷治疗提供了广阔的前景,但目前的研究还存在明显的局限性。要为干细胞干预牙周炎提供更可靠的证据,需要进行更大规模、多中心、双盲、方法可靠的临床试验。
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引用次数: 0
Regenerative Medicine and Nanotechnology approaches against Cardiovascular Diseases: Recent Advances and Future Prospective. 针对心血管疾病的再生医学和纳米技术方法:最新进展与未来展望。
Pub Date : 2024-02-09 DOI: 10.2174/011574888X263530230921074827
Muhammad Waseem Sajjad, Fatima Muzamil, Maida Sabir, Usman Ali Ashfaq

Regenerative medicine refers to medical research focusing on repairing, replacing, or regenerating damaged or diseased tissues or organs. Cardiovascular disease (CVDs) is a significant health issue globally and is the leading cause of death in many countries. According to the Centers for Disease Control and Prevention (CDC), one person dies every 34 seconds in the United States from cardiovascular diseases, and according to a World Health Organization (WHO) report, cardiovascular diseases are the leading cause of death globally, taking an estimated 17.9 million lives each year. Many conventional treatments are available using different drugs for cardiovascular diseases, but these treatments are inadequate. Stem cells and nanotechnology are promising research areas for regenerative medicine treating CVDs. Regenerative medicines are a revolutionary strategy for advancing and successfully treating various diseases, intending to control cardiovascular disorders. This review is a comprehensive study of different treatment methods for cardiovascular diseases using different types of biomaterials as regenerative medicines, the importance of different stem cells in therapeutics, the expanded role of nanotechnology in treatment, the administration of several types of stem cells, their tracking, imaging, and the final observation of clinical trials on many different levels as well as it aims to keep readers up to pace on emerging therapeutic applications of some specific organs and disorders that may improve from regenerative medicine shortly.

再生医学是指以修复、替代或再生受损或患病组织或器官为重点的医学研究。心血管疾病(CVDs)是一个全球性的重大健康问题,也是许多国家的主要死亡原因。根据美国疾病控制和预防中心(CDC)的数据,在美国,每 34 秒就有一人死于心血管疾病,而根据世界卫生组织(WHO)的一份报告,心血管疾病是全球死亡的主要原因,每年约夺走 1,790 万人的生命。对于心血管疾病,目前有许多使用不同药物的传统治疗方法,但这些治疗方法并不充分。干细胞和纳米技术是再生医学治疗心血管疾病的前景广阔的研究领域。再生医学是推进和成功治疗各种疾病的革命性战略,旨在控制心血管疾病。这篇综述全面研究了使用不同类型的生物材料作为再生药物治疗心血管疾病的不同方法、不同干细胞在治疗中的重要性、纳米技术在治疗中的扩展作用、几种干细胞的施用、跟踪、成像和临床试验的最终观察等多个不同层面,并旨在让读者了解一些特定器官和疾病的新兴治疗应用,这些器官和疾病可能会在短期内从再生医学中得到改善。
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引用次数: 0
Nanoparticles' Perspective in Skin Tissue Engineering: Current Concepts and Future Outlook. 纳米粒子在皮肤组织工程中的应用:当前概念与未来展望。
Pub Date : 2024-01-26 DOI: 10.2174/011574888X291345240110102648
Maryam Kaviani, Bita Geramizadeh

Nanotechnology seems to provide solutions to the unresolved complications in skin tissue engineering. According to the broad function of nanoparticles, this review article is intended to build a perspective for future success in skin tissue engineering. In the present review, recent studies were reviewed, and essential benefits and challenging issues regarding the application of nanoparticles in skin tissue engineering were summarized. Previous studies indicated that nanoparticles can play essential roles in the improvement of engineered skin. Bio-inspired design of an engineered skin structure first needs to understand the native tissue and mimic that in laboratory conditions. Moreover, a fundamental comprehension of the nanoparticles and their related effects on the final structure can guide researchers in recruiting appropriate nanoparticles. Attention to essential details, including the designation of nanoparticle type according to the scaffold, how to prepare the nanoparticles, and what concentration to use, is critical for the application of nanoparticles to become a reality. In conclusion, nanoparticles were applied to promote scaffold characteristics and angiogenesis, improve cell behavior, provide antimicrobial conditions, and cell tracking.

纳米技术似乎为皮肤组织工程中尚未解决的复杂问题提供了解决方案。根据纳米粒子的广泛功能,这篇综述文章旨在为皮肤组织工程的未来成功构建一个视角。本综述回顾了最近的研究,总结了纳米粒子在皮肤组织工程中应用的基本优势和挑战性问题。以往的研究表明,纳米粒子在改善工程皮肤方面可发挥重要作用。工程皮肤结构的生物启发设计首先需要了解原生组织,并在实验室条件下模拟原生组织。此外,从根本上了解纳米粒子及其对最终结构的相关影响,可以指导研究人员寻找合适的纳米粒子。注意基本细节,包括根据支架指定纳米粒子类型、如何制备纳米粒子以及使用何种浓度的纳米粒子,对于纳米粒子的应用成为现实至关重要。总之,应用纳米粒子可促进支架特性和血管生成、改善细胞行为、提供抗菌条件和细胞追踪。
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引用次数: 0
Osteogenic Differentiation of Adipose Tissue-Derived Mesenchymal Stem Cells on Composite Polymeric Scaffolds: A Review. 复合聚合物支架上脂肪组织来源间充质干细胞的成骨分化:综述。
Pub Date : 2024-01-25 DOI: 10.2174/011574888X263333231218065453
Saideh Hemati, Mohsen Ghiasi, Ali Salimi

The mesenchymal stem cells (MSCs) are the fundamental part of bone tissue engineering for the emergence of reconstructive medicine. Bone tissue engineering has recently been considered a promising strategy for treating bone diseases and disorders. The technique needs a scaffold to provide an environment for cell attachment to maintain cell function and a rich source of stem cells combined with appropriate growth factors. MSCs can be isolated from adipose tissue (ASCs), bone marrow (BM-MSCs), or umbilical cord (UC-MSCs). In the present study, the potential of ASCs to stimulate bone formation in composite polymeric scaffolds was discussed and it showed that ASCs have osteogenic ability in vitro. The results also indicated that the ASCs have the potential for rapid growth, easier adipose tissue harvesting with fewer donor site complications and high proliferative capacity. The osteogenic differentiation capacity of ASCs varies due to the culture medium and the addition of factors that can change signaling pathways to increase bone differentiation. Furthermore, gene expression analysis has a significant impact on improving our understanding of the molecular pathways involved in ASCs and, thus, osteogenic differentiation. Adding some drugs, such as dexamethasone, to the biomaterial composite also increases the formation of osteocytes. Combining ASCs with scaffolds synthesized from natural and synthetic polymers seems to be an effective strategy for bone regeneration. Applying exopolysaccharides, such as schizophyllan, chitosan, gelatin, and alginate in composite scaffolds enhances the osteogenesis potential of ASCs in bone tissue regeneration.

间充质干细胞(MSCs)是骨组织工程的基本组成部分,是重建医学的基础。近来,骨组织工程被认为是治疗骨病和骨失调的一种有前途的策略。这项技术需要一个支架来提供细胞附着的环境,以维持细胞功能,还需要丰富的干细胞来源和适当的生长因子。间充质干细胞可从脂肪组织(ASCs)、骨髓(BM-MSCs)或脐带(UC-MSCs)中分离。本研究讨论了间充质干细胞在复合聚合物支架中刺激骨形成的潜力,结果表明间充质干细胞具有体外成骨能力。研究结果还表明,间充质干细胞具有快速生长的潜力,更容易采集脂肪组织,供体部位并发症少,增殖能力强。ASCs的成骨分化能力因培养基和添加的因子而异,这些因子可改变信号通路以增加骨分化。此外,基因表达分析对提高我们对参与 ASCs 以及成骨分化的分子通路的认识具有重要影响。在生物材料复合体中添加地塞米松等药物也能增加骨细胞的形成。将 ASCs 与天然及合成聚合物合成的支架相结合似乎是一种有效的骨再生策略。在复合支架中应用外多糖,如五味子聚糖、壳聚糖、明胶和海藻酸盐,可增强 ASCs 在骨组织再生中的成骨潜力。
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引用次数: 0
Insights into the Biological Properties of Prostate Cancer Stem Cells: Implications for Cancer Progression and Therapy 洞察前列腺癌干细胞的生物学特性:前列腺癌干细胞的生物学特性:对癌症进展和治疗的影响
Pub Date : 2024-01-23 DOI: 10.2174/011574888X268997231206112056
Jafar Poodineh, Azimeh Akhlaghpour, Farhoodeh Ghaedrahmati, Fatemeh Khojasteh Pour, Shahab Uddin, Maryam Farzaneh, Shirin Azizidoost

Prostate cancer (PCa) is the second prevalent cancer in men. Recent studies have highlightedthe critical role of prostate cancer stem cells (PCSCs) in driving tumor initiation and metastasisof the prostate tissue. PCSCs are a rare population of cells in the prostate that possess self-renewaland differentiation capabilities, making them a potential therapeutic target for effective PCatreatment. Therefore, targeting PCSCs might be a novel strategy for the treatment of PCs. Researchhas shown that various signaling pathways, such as Notch, SHH, TGF-β, Wnt, STAT3,AKT, and EGFR, are involved in regulating PCSC proliferation, migration, and invasion. Additionally,non-coding RNAs, such as long ncRNAs and miRNAs, have emerged as critical regulatorsof PCSC pathogenesis and drug resistance. Here, we highlight that targeting these pathways couldoffer new opportunities for the management of PCa. This review summarizes the current knowledgesurrounding the essential signaling pathways implicated in PCSC tumorigenesis and invasiveness.

前列腺癌(PCa)是男性第二大高发癌症。最近的研究强调了前列腺癌干细胞(PCSCs)在前列腺组织肿瘤发生和转移中的关键作用。PCSCs 是前列腺中一种罕见的细胞群,具有自我更新和分化能力,是有效治疗 PCa 的潜在治疗靶点。因此,靶向 PCSCs 可能是治疗 PC 病的一种新策略。研究表明,Notch、SHH、TGF-β、Wnt、STAT3、AKT 和表皮生长因子受体(EGFR)等多种信号通路参与调控 PCSC 的增殖、迁移和侵袭。此外,长 ncRNA 和 miRNA 等非编码 RNA 已成为 PCSC 发病机制和耐药性的关键调控因子。在此,我们强调靶向这些通路可为治疗 PCa 提供新的机会。本综述总结了目前围绕与 PCSC 肿瘤发生和侵袭性有关的重要信号通路的知识。
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引用次数: 0
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Current stem cell research & therapy
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