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The Impact of Amotosalen Photochemical Pathogen Inactivation on Human Platelet Lysate 阿莫托沙林光化学病原体灭活对人体血小板裂解液的影响
IF 2.7 4区 医学 Q4 CELL & TISSUE ENGINEERING Pub Date : 2024-06-24 DOI: 10.2174/011574888x307274240610113314
Willem Delabie, Dominique De Bleser, Vicky Vandewalle, Marie-Laurence De Prest, Philippe Vandekerckhove, Veerle Compernolle, Hendrik B. Feys
Background: Human Platelet Lysate (hPL) is a platelet-derived and growth factor-rich supplement for cell culture. It can be prepared from surplus platelet concentrates initially intended for transfusion. Amotosalen-based photochemical pathogen inactivation of platelet concentrates is used in a number of blood establishments worldwide to minimize the risk of pathogen transmission from donor to patient. Method: This pathogen inactivation method has not been formally validated for direct use on hPL. Here, we have studied the impact of pathogen inactivation on hPL and compared it to untreated hPL prepared from pathogen-inactivated platelet concentrates or control hPL. We used mass spectrometry, ELISA, and in vitro mesenchymal stem cell culture for determining residual amotosalen, final growth factor content, and cell doubling, respectively. Result: The data have shown amotosalen concentrations to be reduced a thousand-fold following pathogen inactivation, leaving trace quantities of photosensitizer molecules in the final hPL product. Some growth factors have been reported to be significantly more impacted in hPL that is directly pathogen-inactivated compared to both control conditions. This has no significant effect on the growth kinetics of adipose-derived mesenchymal stem cells. Conclusion: We have concluded direct amotosalen-based pathogen inactivation to have a measurable impact on certain growth factors in hPL, but this does not outweigh the likely benefits of reducing the odds of donor-to-patient pathogen transmission.
背景:人血小板裂解液(hPL)是一种血小板衍生的、富含生长因子的细胞培养补充剂。它可以从最初用于输血的剩余血小板浓缩液中制备。全球许多血液机构都在使用基于阿莫托柳林的血小板浓缩物光化学病原体灭活技术,以最大限度地降低病原体从献血者传染给病人的风险。方法:这种病原体灭活方法尚未正式验证是否可直接用于 hPL。在此,我们研究了病原体灭活对 hPL 的影响,并将其与未经处理的病原体灭活血小板浓缩物制备的 hPL 或对照 hPL 进行了比较。我们使用质谱法、酶联免疫吸附法和体外间充质干细胞培养法分别测定了残留的阿莫托沙林、最终生长因子含量和细胞倍增。结果数据显示,在病原体失活后,阿莫托沙林的浓度降低了一千倍,最终的 hPL 产品中还残留着微量的光敏剂分子。据报道,与两种对照条件相比,病原体直接失活的 hPL 对某些生长因子的影响更大。这对脂肪间充质干细胞的生长动力学没有明显影响。结论我们得出结论,基于阿莫托品的直接病原体灭活对hPL中的某些生长因子有可测量的影响,但这并不能抵消降低捐献者向患者传播病原体几率可能带来的益处。
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引用次数: 0
Umbilical Cord Blood and UC-MSCs Combined with Low-Dose Immunosuppressant in the Treatment of Elderly Patients with Pure Red Cell Aplastic: A Case Series 脐带血和造血干细胞联合小剂量免疫抑制剂治疗老年纯红细胞再生不良患者:病例系列
IF 2.7 4区 医学 Q4 CELL & TISSUE ENGINEERING Pub Date : 2024-05-03 DOI: 10.2174/011574888x290378240424075002
Wei-Wei Zhu, Sujing Zhuang, Zhe Yu, Xin Li, Tian-Jie Han, Yue Ma, Li-Jun Li, Zhi-Rui Zhao
Introduction: At present, cyclosporine (CsA) is the first-line treatment for Pure Red Cell Aplasia (PRCA), but CsA administration can be associated with a number of side effects due to its high toxicity. Therefore, it is urgent to explore a safe and effective treatment for elderly patients who cannot be treated with conventional doses of CsA, especially those with multiple complications. Allogeneic Stem Cell Transplantation (ASCT) for PRCA is a promising treatment, but reports of using umbilical cord blood (UCB) are very rare. Case Presentation: In this report, UCB and umbilical cord mesenchymal stem cells (UC-MSCs) combined with low-dose CsA (1-3mg/kg/d) were used to treat 3 elderly patients who were diagnosed with PRCA combined with multiple complications in heart, lung, and renal. The treatments were successful without complications, and 12 months after stem cell infusion, the blood tests of the patients came normal. Moreover, the function of the liver, heart, and kidney continued to be stable. Conclusion: This report provides an effective regimen of using UCB and UC-MSCs combined with low-dose CsA (1-3 mg/kg/d) to treat PRCA, especially for elderly patients with multiple complications who cannot use the conventional dosage.
导言:目前,环孢素(CsA)是治疗纯红细胞增生症(PRCA)的一线药物,但由于 CsA 毒性大,服用后会产生一系列副作用。因此,对于无法使用常规剂量 CsA 治疗的老年患者,尤其是有多种并发症的患者,迫切需要探索一种安全有效的治疗方法。同种异体干细胞移植(ASCT)治疗PRCA是一种很有前景的治疗方法,但使用脐带血(UCB)的报道非常罕见。病例介绍:本报告采用 UCB 和脐带间充质干细胞(UC-MSCs)联合小剂量 CsA(1-3 毫克/千克/天)治疗 3 例老年 PRCA 合并心、肺、肾多种并发症患者。干细胞输注 12 个月后,患者的血液化验结果正常。此外,肝脏、心脏和肾脏的功能继续保持稳定。结论本报告提供了一种使用UCB和UC-间充质干细胞联合低剂量CsA(1-3 mg/kg/d)治疗PRCA的有效方案,尤其适用于无法使用常规剂量的有多种并发症的老年患者。
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引用次数: 0
Albiflorin Inhibits Advanced Glycation End Products-Induced ROS and MMP-1 Expression in Gingival Fibroblasts 阿比福林抑制高级糖化终产物诱导的 ROS 和 MMP-1 在牙龈成纤维细胞中的表达
IF 2.7 4区 医学 Q4 CELL & TISSUE ENGINEERING Pub Date : 2024-04-30 DOI: 10.2174/011574888x302174240420165019
Linlin Gao, Wenqi Fu, Yanyan Liu, Lili Fan, Shiwei Liu, Nan Zhang
Background: Periodontitis is a common complication of diabetes, with advanced glycation end products (AGEs) playing a key role in its pathogenesis. Albiflorin, a monoterpene glycoside, has shown potential anti-inflammatory and antioxidant properties. This study aims to investigate the effects of albiflorin on AGEs-induced gingival fibroblasts and its underlying mechanisms. Objective: This study aimed to evaluate the role of albiflorin in mitigating ROS production, inflammation, and MMP-1 expression in AGEs-induced gingival fibroblasts. objective: / Methods: The viability of gingival fibroblasts treated with albiflorin and AGEs was assessed using CCK-8 assays. ROS levels were measured by DCF staining, and the expression of inflammatory markers and MMP-1 was evaluated by ELISA and qPCR. The involvement of the NF-κB and Nrf2 pathways was examined by immunoblotting. Results: Albiflorin enhanced the viability of AGEs-induced gingival fibroblasts and reduced ROS production. It also decreased the expression of IL-6, IL-8, RAGE, and MMP-1, suggesting an anti- inflammatory effect. Mechanistically, albiflorin modulated the NF-κB and Nrf2 pathways in AGEs-induced gingival fibroblasts. Conclusion: Albiflorin exhibited protective effects against AGEs-induced oxidative stress and inflammation in gingival fibroblasts, highlighting its potential as a therapeutic agent for periodontitis in diabetic patients. The modulation of the NF-κB and Nrf2 pathways by albiflorin provides insight into its mechanism of action. other: /
背景:牙周炎是糖尿病的常见并发症,而高级糖化终产物(AGEs)在其发病机制中起着关键作用。白花前胡素是一种单萜苷,具有潜在的抗炎和抗氧化特性。本研究旨在探讨白花蛇舌草素对 AGEs 诱导的牙龈成纤维细胞的影响及其内在机制。研究目的本研究旨在评估白花蛇舌草素在减轻 AGE 诱导的牙龈成纤维细胞中 ROS 生成、炎症和 MMP-1 表达方面的作用。目的:/方法:/白花蛇舌草素在减轻 AGE 诱导的牙龈成纤维细胞中 ROS 生成、炎症和 MMP-1 表达方面的作用:/ 方法:使用 CCK-8 检测法评估经阿比福林和 AGEs 处理的牙龈成纤维细胞的活力。用 DCF 染色法测量 ROS 水平,用 ELISA 和 qPCR 评估炎症标志物和 MMP-1 的表达。免疫印迹法检测了 NF-κB 和 Nrf2 通路的参与情况。结果阿维菌素能增强 AGE 诱导的牙龈成纤维细胞的活力并减少 ROS 的产生。它还能降低 IL-6、IL-8、RAGE 和 MMP-1 的表达,这表明它具有抗炎作用。从机理上讲,阿维菌素调节了 AGE 诱导的牙龈成纤维细胞中的 NF-κB 和 Nrf2 通路。结论白花蛇舌草素对 AGE 诱导的牙龈成纤维细胞氧化应激和炎症具有保护作用,突出了其作为糖尿病患者牙周炎治疗剂的潜力。白花前胡素对 NF-κB 和 Nrf2 通路的调节作用使人们对其作用机制有了更深入的了解:/
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引用次数: 0
Unlocking the Potential of Induced Pluripotent Stem Cells in Revolutionizing Cancer Therapy 释放诱导多能干细胞的潜力,彻底改变癌症疗法
IF 2.7 4区 医学 Q4 CELL & TISSUE ENGINEERING Pub Date : 2024-04-17 DOI: 10.2174/011574888x294791240408055222
Amrita Mondal, Ankita Talukdar, Rizwanul Haque
: Induced Pluripotent Stem Cells (iPSCs) are among the top versatile implements of biomedical research. Stem cell science has made strides over the past few years, emerging as a new opportunity to treat cancer, and many such continuous initiatives have been made into clinical trials. As the global mortality rate is too high despite the effectiveness of prevalent cancer therapies, this review explores the potential of iPSC in different aspects of cancer-related areas. The preparation of iPSCs, including their derivation from cancer stem cells, was covered after establishing the intricacy of current cancer treatments. This article highlights the potential of iPSC- based NK cells and dendritic cells for immunotherapy and delves into the role of iPSC-based mesenchymal cells in targeted therapy. The potential of iPSC-derived organoids as a vital tool for disease modeling and drug discovery has been showcased, and the importance of iPSC-based cancer vaccines is also emphasized. The ongoing clinical trials of iPSC-based cancer treatment have also been highlighted. Though much work remains to be done to implicate these iPSC-based therapeutic options from research labs to clinics and hospitals, ongoing studies and clinical/translational follow-ups raise hope for novel cancer therapies employing iPSC technology.
:诱导多能干细胞(iPSCs)是生物医学研究中最重要的多用途工具之一。干细胞科学在过去几年中取得了长足进步,成为治疗癌症的新契机,许多此类持续性研究已进入临床试验阶段。尽管流行的癌症疗法效果显著,但全球死亡率仍然居高不下,因此本综述探讨了 iPSC 在癌症相关领域不同方面的潜力。在确定了当前癌症治疗的复杂性之后,文章介绍了 iPSC 的制备,包括从癌症干细胞中提取 iPSC。本文强调了基于 iPSC 的 NK 细胞和树突状细胞在免疫疗法中的潜力,并深入探讨了基于 iPSC 的间充质细胞在靶向疗法中的作用。文章展示了 iPSC 衍生的器官组织作为疾病建模和药物发现重要工具的潜力,还强调了基于 iPSC 的癌症疫苗的重要性。会议还重点介绍了正在进行的基于 iPSC 的癌症治疗临床试验。虽然要将这些基于 iPSC 的治疗方案从研究实验室推广到诊所和医院还有很多工作要做,但正在进行的研究和临床/横向跟踪为采用 iPSC 技术的新型癌症疗法带来了希望。
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引用次数: 0
Outcomes of Patients with Heavily Pretreated Relapsed/Refractory Multiple Myeloma Receiving Salvage Cytotoxic Therapy with Supportive Stem Cell Boost 接受挽救性细胞毒性疗法并辅助干细胞强化治疗的重症复发/难治性多发性骨髓瘤患者的疗效
IF 2.7 4区 医学 Q4 CELL & TISSUE ENGINEERING Pub Date : 2024-04-05 DOI: 10.2174/011574888x287532240325041249
Ayrton Bangolo, Samir Oza, Ronit Slotky, Aimee Chappell, David Siegel, Harsh Parmar, Noa Biran, David H. Vesole, Pooja Phull
Background: Multiple myeloma (MM) is an incurable hematologic malignancy characterized by the neoplastic proliferation of plasma cells, which produce monoclonal immunoglobulin that can cause vital organ damage, subsequently leading to significant morbidity and mortality. Autologous hematopoietic stem cell transplant (ASCT) is the standard-of-care management of eligible patients with newly diagnosed MM. Experts recommend collecting enough stem cells upfront to support a possible tandem transplant, salvage ASCT, or a stem cell “boost” to allow for the administration of multiagent cytotoxic chemotherapy in patients with relapsed/refractory disease. background: Multiple myeloma (MM) is an incurable hematologic malignancy characterized by the neoplastic proliferation of plasma cells which produce monoclonal immunoglobulin that can cause vital organ damage, subsequently leading to significant morbidity and mortality. Autologous hematopoietic stem cell transplant (ASCT) is the standard-of-care management of eligible patients with newly diagnosed MM. Experts recommend collecting enough stem cells upfront to support a possible tandem transplant, salvage ASCT, or a stem cell “boost” to allow for the administration of multiagent cytotoxic chemotherapy in patients with relapsed/refractory disease. Objective: There is currently a paucity of data on the response rates and outcomes of patients with relapsed MM who undergo cytotoxic chemotherapy followed by a stem cell boost; this study examines the outcomes of patients treated with this approach. Methods: We conducted a retrospective chart review from two oncologic treatment centers in the United States of adult patients who underwent a first ASCT between 1999 and 2021 and subsequently received cytotoxic chemotherapy followed by stem cell boost further on in their disease course. Survival analysis was carried out using the Kaplan-Meier method, and the log-rank test was used to compare survival curves. Results: We found that the majority (56.6%) of these patients responded to therapy and that 60.6% of these patients were able to receive at least one subsequent line of therapy post-boost. Furthermore, patients who responded to therapy had significantly longer median overall survival compared to those who did not respond (323 days vs 93 days, p=0.0045), and age did not affect response to therapy. Conclusion: This data allow clinicians to appropriately implement and inform patients of the therapeutic uses and clinical outcomes of stem cell boost in patients with multiply relapsed/refractory MM.
背景:多发性骨髓瘤(MM)是一种无法治愈的血液系统恶性肿瘤:多发性骨髓瘤(MM)是一种无法治愈的血液系统恶性肿瘤,其特征是浆细胞的肿瘤性增殖,浆细胞产生的单克隆免疫球蛋白可造成重要器官损伤,从而导致严重的发病率和死亡率。自体造血干细胞移植(ASCT)是治疗符合条件的新诊断MM患者的标准方法。专家建议先收集足够的干细胞,以支持可能的串联移植、挽救性ASCT或干细胞 "增量",以便对复发/难治性疾病患者进行多药细胞毒性化疗:多发性骨髓瘤(MM)是一种无法治愈的血液系统恶性肿瘤,其特征是浆细胞的肿瘤性增生,浆细胞产生的单克隆免疫球蛋白可导致重要器官损伤,进而导致严重的发病率和死亡率。自体造血干细胞移植(ASCT)是治疗符合条件的新诊断 MM 患者的标准方法。专家建议前期收集足够的干细胞,以支持可能的串联移植、挽救性ASCT或干细胞 "增量",以便对复发/难治性疾病患者进行多药细胞毒性化疗。目的:目前,有关复发性骨髓瘤患者接受细胞毒性化疗后再进行干细胞增效治疗的反应率和疗效的数据很少;本研究探讨了采用这种方法治疗的患者的疗效。方法:我们对美国两家肿瘤治疗中心1999年至2021年间接受首次ASCT治疗、随后接受细胞毒性化疗和干细胞增效治疗的成年患者进行了回顾性病历审查。采用卡普兰-梅耶法进行生存分析,并用对数秩检验比较生存曲线。结果我们发现,这些患者中的大多数(56.6%)对治疗有反应,其中 60.6% 的患者能够在增效后接受至少一种后续治疗。此外,对治疗有反应的患者的中位总生存期明显长于没有反应的患者(323 天 vs 93 天,P=0.0045),而年龄并不影响对治疗的反应。结论临床医生可根据这些数据,对多次复发/难治性MM患者适当实施干细胞促进疗法,并告知患者其治疗用途和临床结果。
{"title":"Outcomes of Patients with Heavily Pretreated Relapsed/Refractory Multiple Myeloma Receiving Salvage Cytotoxic Therapy with Supportive Stem Cell Boost","authors":"Ayrton Bangolo, Samir Oza, Ronit Slotky, Aimee Chappell, David Siegel, Harsh Parmar, Noa Biran, David H. Vesole, Pooja Phull","doi":"10.2174/011574888x287532240325041249","DOIUrl":"https://doi.org/10.2174/011574888x287532240325041249","url":null,"abstract":"Background: Multiple myeloma (MM) is an incurable hematologic malignancy characterized by the neoplastic proliferation of plasma cells, which produce monoclonal immunoglobulin that can cause vital organ damage, subsequently leading to significant morbidity and mortality. Autologous hematopoietic stem cell transplant (ASCT) is the standard-of-care management of eligible patients with newly diagnosed MM. Experts recommend collecting enough stem cells upfront to support a possible tandem transplant, salvage ASCT, or a stem cell “boost” to allow for the administration of multiagent cytotoxic chemotherapy in patients with relapsed/refractory disease. background: Multiple myeloma (MM) is an incurable hematologic malignancy characterized by the neoplastic proliferation of plasma cells which produce monoclonal immunoglobulin that can cause vital organ damage, subsequently leading to significant morbidity and mortality. Autologous hematopoietic stem cell transplant (ASCT) is the standard-of-care management of eligible patients with newly diagnosed MM. Experts recommend collecting enough stem cells upfront to support a possible tandem transplant, salvage ASCT, or a stem cell “boost” to allow for the administration of multiagent cytotoxic chemotherapy in patients with relapsed/refractory disease. Objective: There is currently a paucity of data on the response rates and outcomes of patients with relapsed MM who undergo cytotoxic chemotherapy followed by a stem cell boost; this study examines the outcomes of patients treated with this approach. Methods: We conducted a retrospective chart review from two oncologic treatment centers in the United States of adult patients who underwent a first ASCT between 1999 and 2021 and subsequently received cytotoxic chemotherapy followed by stem cell boost further on in their disease course. Survival analysis was carried out using the Kaplan-Meier method, and the log-rank test was used to compare survival curves. Results: We found that the majority (56.6%) of these patients responded to therapy and that 60.6% of these patients were able to receive at least one subsequent line of therapy post-boost. Furthermore, patients who responded to therapy had significantly longer median overall survival compared to those who did not respond (323 days vs 93 days, p=0.0045), and age did not affect response to therapy. Conclusion: This data allow clinicians to appropriately implement and inform patients of the therapeutic uses and clinical outcomes of stem cell boost in patients with multiply relapsed/refractory MM.","PeriodicalId":10979,"journal":{"name":"Current stem cell research & therapy","volume":"49 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140567609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The Renoprotective and Anti-Inflammatory Effects of Human Urine-Derived Stem Cells on Acute Kidney Injury Animals 人尿干细胞对急性肾损伤动物的肾保护和抗炎作用
IF 2.7 4区 医学 Q4 CELL & TISSUE ENGINEERING Pub Date : 2024-04-04 DOI: 10.2174/011574888x296559240326063705
Yuanyuan Kuang, Chenyu Fan, Xiaojun Long, Jiajia Zheng, Yunsi Zeng, Yuhui Wei, Jiasheng Zhang, Shuangjin Yu, Tong Chen, Hehuan Ruan, Yi Wang, Ning Na, Yiming Zhou, Jiang Qiu
Background: Acute Kidney Injury (AKI) is defined as a sudden loss of kidney function, which is often caused by drugs, toxins, and infections. The large spectrum of AKI implies diverse pathophysiological mechanisms. In many cases, AKI can be lethal, and kidney replacement therapy is frequently needed. However, current treatments are not satisfying. Developing novel therapies for AKI is essential. Adult stem cells possess regenerative ability and play an important role in medical research and disease treatment. background: Acute kidney injury (AKI) is defined by a sudden loss of kidney function, which is often caused by drugs, toxins, and infections. The large spectrum of AKI implies diverse pathophysiological mechanisms. In many cases, AKI can be lethal, and kidney replacement therapy is frequently needed. However, current treatments are not satisfying. Methods: In this study, we isolated and characterized a distinct human urine-derived stem cell, which expressed both proximal tubular cell and mesenchymal stem cell genes as well as certain unique genes. objective: Developing novel therapies for AKI is essential. Adult stem cells possess regenerative powers and play an important role in medical research and disease treatment. Results: It was found that these cells exhibited robust protective effects on tubular cells and anti- inflammatory effects on macrophages in vitro. In an ischemia-reperfusion-induced acute kidney injury NOD-SCID mouse model, transplantation of USCs significantly protected the kidney morphology and functions in vivo. method: Here we isolated and characterized a distinct human urine-derived stem cell, which expresses both proximal tubular cell and mesenchymal stem cell genes as well as certain unique genes. Conclusion: In summary, our results highlighted the effectiveness of USCs in protecting from PTC injury and impeding macrophage polarization, as well as the secretion of pro-inflammatory interleukins, suggesting the potential of USCs as a novel cell therapy in AKI. result: We discovered that these cells exhibited robust protective effects on tubular cells and anti-inflammatory effects on macrophages in vitro. In an ischemia-reperfusion induced acute kidney injury mouse model, transplantation of USCs significantly protected the kidney morphology and functions in vivo.
背景:急性肾损伤(AKI)是指肾功能突然丧失,通常由药物、毒素和感染引起。急性肾损伤的病理生理机制多种多样。在许多情况下,AKI 可导致死亡,因此经常需要进行肾脏替代治疗。然而,目前的治疗方法并不能令人满意。开发治疗AKI的新疗法至关重要。成体干细胞具有再生能力,在医学研究和疾病治疗中发挥着重要作用:急性肾损伤(AKI)是指肾功能突然丧失,通常由药物、毒素和感染引起。AKI 的病理生理机制多种多样。在许多情况下,AKI 可导致死亡,因此经常需要进行肾脏替代治疗。然而,目前的治疗方法并不令人满意。方法:在这项研究中,我们分离并鉴定了一种独特的人类尿源干细胞,它同时表达近端肾小管细胞和间充质干细胞基因以及某些独特的基因:开发治疗AKI的新型疗法至关重要。成人干细胞具有再生能力,在医学研究和疾病治疗中发挥着重要作用。结果:研究发现,这些细胞在体外对肾小管细胞有很强的保护作用,对巨噬细胞有抗炎作用。在缺血再灌注诱导的急性肾损伤 NOD-SCID 小鼠模型中,移植 USCs 能显著保护体内肾脏的形态和功能:我们在此分离并鉴定了一种独特的人类尿源干细胞,它同时表达近端肾小管细胞和间充质干细胞基因以及某些独特的基因。结论:总之,我们的研究结果突显了 USC 在保护 PTC 损伤、抑制巨噬细胞极化以及促炎性白细胞介素分泌方面的有效性,这表明 USC 有可能成为治疗 AKI 的新型细胞疗法:我们发现,这些细胞在体外对肾小管细胞有很强的保护作用,对巨噬细胞有抗炎作用。在缺血再灌注诱导的急性肾损伤小鼠模型中,移植 USCs 能显著保护体内肾脏的形态和功能。
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引用次数: 0
Bone Marrow Mesenchymal Stem Cell-derived Exosomal microRNA- 99b-5p Promotes Cell Growth of High Glucose-treated Human Umbilical Vein Endothelial Cells by Modulating THAP Domain Containing 2 Expression 骨髓间充质干细胞衍生的外泌体 microRNA- 99b-5p 通过调节 THAP 含域 2 的表达促进高血糖处理的人脐静脉内皮细胞的生长
IF 2.7 4区 医学 Q4 CELL & TISSUE ENGINEERING Pub Date : 2024-02-04 DOI: 10.2174/011574888x272011231128073104
Hongru Ruan, Hui Shi, Wenkang Luan, Sida Pan
Introduction: Bone marrow mesenchymal stem cell-derived exosomes (BMSC-exos) may function as novel candidates for treating diabetic wounds due to their ability to promote angiogenesis. Materials and Methods: This study investigated the effects of BMSC-exos on the growth and metastasis of human umbilical vein endothelial cells (HUVECs) treated with high glucose (HG). The exosomes were separated from BMSCs and identified. The cell phenotype was detected by 3-(4,5- dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide and 5-ethynyl-2’-deoxyuridine, wound healing, and transwell assays, while the number of tubes was measured via tube formation assay. objective: The exosomes were separated from BMSCs and identified. Result: The RNA and protein expression levels were studied using reverse transcription-quantitative polymerase chain reaction and western blotting, whereas integration of microRNA-99b-5p (miR-99b-5p) with THAP domain containing 2 (THAP2) was confirmed via dual-luciferase reporter and RNA pull-down assays. Results of transmission electron microscopy, nanoparticle tracking analysis, and laser scanning confocal microscopy revealed that exosomes were successfully separated from BMSCs and endocytosed into the cytoplasm by HUVECs. Similarly, BMSC-exos were found to promote the growth of HG-treated HUVECs, while their growth was inhibited by suppressing miR-99b-5p. THAP2 was found to bind to miR-99b-5p, where THAP2 inhibition reversed the miR-99b-5p-induced effects on cell growth, migration, and tube numbers. Conclusion: In conclusion, miR-99b-5p in BMSC-exo protects HUVECs by negatively regulating THAP2 expression.
导言:骨髓间充质干细胞衍生的外泌体(BMSC-exos)具有促进血管生成的能力,可作为治疗糖尿病伤口的新型候选物质。材料与方法:本研究调查了BMSC-外泌体对经高糖(HG)处理的人脐静脉内皮细胞(HUVECs)的生长和转移的影响。外泌体从 BMSCs 中分离并鉴定。细胞表型通过 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基溴化四氮唑和 5-乙炔基-2'-脱氧尿苷、伤口愈合和透孔试验进行检测,而细胞管的数量则通过细胞管形成试验进行测量:从 BMSCs 中分离并鉴定外泌体。结果:利用反转录定量聚合酶链反应和 Western 印迹法研究了 RNA 和蛋白质的表达水平,并通过双荧光素酶报告和 RNA 牵引试验证实了 microRNA-99b-5p (miR-99b-5p)与含 THAP 结构域 2 (THAP2)的整合。透射电子显微镜、纳米粒子跟踪分析和激光扫描共聚焦显微镜的结果显示,外泌体成功地从 BMSCs 中分离出来,并被 HUVECs 内吞到细胞质中。同样,研究发现 BMSC 外泌体能促进经 HG 处理的 HUVEC 的生长,而抑制 miR-99b-5p 则会抑制 HUVEC 的生长。研究发现 THAP2 与 miR-99b-5p 结合,抑制 THAP2 可逆转 miR-99b-5p 诱导的对细胞生长、迁移和管数量的影响。结论总之,BMSC-exo 中的 miR-99b-5p 可通过负调控 THAP2 的表达来保护 HUVEC。
{"title":"Bone Marrow Mesenchymal Stem Cell-derived Exosomal microRNA- 99b-5p Promotes Cell Growth of High Glucose-treated Human Umbilical Vein Endothelial Cells by Modulating THAP Domain Containing 2 Expression","authors":"Hongru Ruan, Hui Shi, Wenkang Luan, Sida Pan","doi":"10.2174/011574888x272011231128073104","DOIUrl":"https://doi.org/10.2174/011574888x272011231128073104","url":null,"abstract":"Introduction: Bone marrow mesenchymal stem cell-derived exosomes (BMSC-exos) may function as novel candidates for treating diabetic wounds due to their ability to promote angiogenesis. Materials and Methods: This study investigated the effects of BMSC-exos on the growth and metastasis of human umbilical vein endothelial cells (HUVECs) treated with high glucose (HG). The exosomes were separated from BMSCs and identified. The cell phenotype was detected by 3-(4,5- dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide and 5-ethynyl-2’-deoxyuridine, wound healing, and transwell assays, while the number of tubes was measured via tube formation assay. objective: The exosomes were separated from BMSCs and identified. Result: The RNA and protein expression levels were studied using reverse transcription-quantitative polymerase chain reaction and western blotting, whereas integration of microRNA-99b-5p (miR-99b-5p) with THAP domain containing 2 (THAP2) was confirmed via dual-luciferase reporter and RNA pull-down assays. Results of transmission electron microscopy, nanoparticle tracking analysis, and laser scanning confocal microscopy revealed that exosomes were successfully separated from BMSCs and endocytosed into the cytoplasm by HUVECs. Similarly, BMSC-exos were found to promote the growth of HG-treated HUVECs, while their growth was inhibited by suppressing miR-99b-5p. THAP2 was found to bind to miR-99b-5p, where THAP2 inhibition reversed the miR-99b-5p-induced effects on cell growth, migration, and tube numbers. Conclusion: In conclusion, miR-99b-5p in BMSC-exo protects HUVECs by negatively regulating THAP2 expression.","PeriodicalId":10979,"journal":{"name":"Current stem cell research & therapy","volume":"12 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139688938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A Novel Multi-compartment Rotating Bioreactor for Improving ADSC--Spheroid Formation and its Application in Neurogenic Erectile Dysfunction 改善 ADSC 球形形成的新型多室旋转生物反应器及其在神经源性勃起功能障碍中的应用
IF 2.7 4区 医学 Q4 CELL & TISSUE ENGINEERING Pub Date : 2024-02-04 DOI: 10.2174/011574888x253599231126161254
Peng Wang, Yang Liu, Xiao-Feng Duan, Xiao-Ying Pan, Xiang-Rui Kong, Yong Yang
Objective: The aim of this study was to construct a multicompartment synchronous rotating bioreactor (MCSRB) for batch-production of homogenized adipose-derived stem cell (ADSC) microspheres and treat neurogenic erectile dysfunction (ED). background: Erectile dysfunction due to cavernous nerve injury is commonly associated with pelvic site surgery1, particularly radical prostatectomy, which is one of the most common first-line treatments for men with limited and locally progressive prostate cancer, with a probability of 14-82% of causing erectile dysfunction after surgery, severely affecting patients' quality of life. For this neurogenic erectile dysfunction, the traditional first-line treatment with phosphodiesterase type 5 (PDE5) inhibitors is ineffective and has side effects such as headache, dizziness, and indigestion; thus, there is an urgent need to find a new alternative therapy. In recent years, with the rise of stem cell therapy, the application of stem cells to the treatment of erectile dysfunction has attracted extra attention. Zhang et al. showed that a cytokine secreted by adipose tissue-derived stem cells has a neurotrophic effect on cavernous nerve regeneration. It has also been shown that intravenous infusion of bone marrow-derived mesenchymal stem cells (MSCs) attenuates erectile dysfunction after cavernous nerve injury in rats. However, because of the loose pore-like structure of the penile corpus cavernosum, stem cells injected via the corpus cavernosum carry the risk of cell escape, leading to pulmonary embolism; thus, this issue of safety and limited treatment due to cell escape warrants intensive study. It has been shown that culturing MSCs into 3D stem cell microspheres can significantly activate their paracrine function, which is important for improving the therapeutic potential of MSCs, while Xu's study showed that stem cell microspheres can increase cell retention in the cavernous body and reduce the risk of pulmonary embolism. Previous studies have found that stem cell microspheres can enhance paracrine, anti-inflammatory, and anti-apoptotic functions. Currently, there are many methods for 3D sphere formation of stem cells, such as the suspension droplet method, micropatterning method and microfluidic method, but all of these methods have deficiencies, such as low yield, low recovery of culture medium and the need for special equipment. The multicompartment synchronized rotating bioreactor is a device designed and developed by our team to culture MSC microspheres in 3D. During our experiments, we found that the dynamic culture of 3D stem microspheres using the MCSRB is very simple and convenient, and the design of multiple compartments scales well, which can greatly improve the efficiency and reduce the time of determining the optimal conditions during culture, and significantly improves MSC paracrine function. Therefore, in this study, we investigated whether the dynamic culture of dry 3D microspheres
研究目的本研究旨在构建多室同步旋转生物反应器(MCSRB),用于批量生产均质化脂肪来源干细胞(ADSC)微球,治疗神经源性勃起功能障碍(ED):海绵体神经损伤导致的勃起功能障碍常见于盆腔部位手术1,尤其是根治性前列腺切除术,这是男性局限性和局部进展性前列腺癌最常见的一线治疗方法之一,术后引起勃起功能障碍的概率为14%-82%,严重影响患者的生活质量&#039;。对于这种神经源性勃起功能障碍,传统的5型磷酸二酯酶(PDE5)抑制剂一线治疗效果不佳,且有头痛、头晕、消化不良等副作用,因此迫切需要寻找一种新的替代疗法。近年来,随着干细胞疗法的兴起,干细胞在勃起功能障碍治疗中的应用引起了人们的格外关注。Zhang等人的研究表明,脂肪组织来源的干细胞分泌的一种细胞因子对海绵体神经再生具有神经营养作用。也有研究表明,静脉注射骨髓间充质干细胞(MSCs)可减轻大鼠海绵体神经损伤后的勃起功能障碍。然而,由于阴茎海绵体具有疏松的孔状结构,经海绵体注入的干细胞存在细胞逃逸的风险,可能导致肺栓塞;因此,因细胞逃逸而导致的安全性和治疗受限问题值得深入研究。有研究表明,将间叶干细胞培养成三维干细胞微球能显著激活其旁分泌功能,这对提高间叶干细胞的治疗潜力非常重要,而Xu&#039;的研究表明,干细胞微球能增加细胞在海绵体内的存留,降低肺栓塞的风险。以往的研究发现,干细胞微球可增强旁分泌、抗炎和抗凋亡功能。目前,干细胞三维成球的方法很多,如悬浮液滴法、微图案法和微流体法等,但这些方法都存在产量低、培养液回收率低、需要特殊设备等不足。多室同步旋转生物反应器是我们团队设计开发的一种三维培养间充质干细胞微球的装置。在实验过程中,我们发现利用多室同步旋转生物反应器进行三维干细胞微球的动态培养非常简单方便,多室的设计扩展性好,可以大大提高培养效率,减少培养过程中确定最佳条件的时间,显著提高间充质干细胞的旁分泌功能。因此,本研究探讨了在该生物反应器中动态培养干性三维微球能否有效恢复海绵体神经损伤大鼠的勃起功能及病理变化。研究方法首先,利用离心装置和铰链托盘构建了一个 MCSRB。其次,探讨了影响 ADSC-球体形成的因素(密度、转速)。最后,建立了神经源性 ED 模型,以验证 ADSC-spheroids 治疗 ED 的有效性和安全性:研究在多室同步旋转生物反应器(MCSRB)中动态培养的大鼠脂肪干细胞(ADSC)微球对双侧海绵体神经损伤诱发的勃起功能障碍大鼠的治疗效果。结果多室同步旋转生物反应器促进 ADSCs 形成微球,大多数微球直径为 90-130 μm。与对照组相比,三维培养的上清液使 ADSCs 的细胞因子表达和人脐静脉内皮细胞(HUVECs)的迁移率显著增加。与传统 ADSCs 治疗组相比,ADSC-spheroids 治疗组的阴茎勃起功能和病理变化均有所改善(p < 0.01)。结论使用MCSRB装置可高效、批量、可控、均质化生产ADSC干细胞微球,并有效改善神经源性大鼠的勃起功能障碍:用MCSRB动态培养的三维ADSC微球治疗神经源性大鼠勃起功能障碍,能显著改善勃起功能障碍,并促进组织损伤的恢复,证明了干细胞微球的规模化培养价值和潜在的临床应用前景。
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引用次数: 0
Effect of Pioglitazone and Cetuximab on Colon Cancer Stem-like Cell (CCSLCs) Properties 吡格列酮和西妥昔单抗对结肠癌干样细胞特性的影响
IF 2.7 4区 医学 Q4 CELL & TISSUE ENGINEERING Pub Date : 2024-02-02 DOI: 10.2174/011574888x283318240118111822
Nasim Alamdar, Shirin Farivar, Kaveh Baghaei, Amir Ali Hamidieh, Hossein Soltaninejad, Hamid Asadzadeh Aghdaei, Mohammadreza Zali, Zohreh Saltanatpour
Background: One of the main reasons for cancer resistance to chemotherapy is the presence of cancer stem cells (CSCs) in cancer tissues. It is also believed that CSCs are the unique originators of all tumor cells. On the other hand, the Epithelial-Mesenchymal Transition pathway (EMT) can act as the main agent of metastasis. Therefore, it is possible that targeting CSCs as well as the EMT pathway could help in cancer therapy. Considering that CSCs constitute only a small percentage of the total tumor mass, enrichment before study is necessary. In our previous study, CSCs were enriched in the human colon cancer cell line HT29 by induction of EMT. These CSC-enriched HT29 cells with mesenchymal morphology were named “HT29-shE”. In the present study, these cells were used to investigate the effect of pioglitazone (Pio) and Cetuximab (Cet) in order to find CSC and EMT targeting agents. Method: The viability and IC50 rate of cells treated with different concentrations of Pio and Cet were evaluated using the MTT test. EMT and CSC markers and cell morphology were assessed in Pio and Cet treated and untreated HT29-shE cells using flow cytometry, realtime PCR, immunocytochemistry, and microscopic monitoring. Results: The findings showed that Pio and Cet at concentrations of 250 μM and 40 μg/ml, respectively, decrease cell viability by 50%. Also, they were able to reduce the expression of CSC markers (CD133 and CD44) in the CSC enriched HT29 cell line. Furthermore, Pio and Cet could efficiently reduce the expression of vimentin as a mesenchymal marker and significantly upregulate the expression of E-cadherin as an epidermal marker of EMT and its reverse mesenchymal-- to-epithelial transition (MET). In addition, the mesenchymal morphology of HT29-shE changed into epithelial morphology after Cet treatment. Conclusion: Pio and Cet could inhibit EMT and reduce CSC markers in the EMT induced/CSC enriched cell line. We expect that focus on finding EMT/CSC-targeting agents like these drugs can be helpful for cancer treatment.
背景:癌症对化疗产生耐药性的主要原因之一是癌症组织中存在癌症干细胞(CSCs)。人们还认为,癌干细胞是所有肿瘤细胞的独特起源。另一方面,上皮-间质转化途径(EMT)可作为转移的主要因素。因此,靶向 CSCs 和 EMT 通路可能有助于癌症治疗。考虑到 CSCs 只占肿瘤总量的一小部分,因此在研究前有必要进行富集。在我们之前的研究中,通过诱导 EMT,人结肠癌细胞系 HT29 中的 CSCs 得到了富集。这些具有间质形态的 CSC 富集 HT29 细胞被命名为 "HT29-shE"。在本研究中,这些细胞被用来研究吡格列酮 (Pio) 和西妥昔单抗 (Cet) 的作用,以寻找 CSC 和 EMT 靶向药物。研究方法使用 MTT 试验评估不同浓度 Pio 和 Cet 处理的细胞的活力和 IC50 率。使用流式细胞术、实时 PCR、免疫细胞化学和显微镜监测评估经 Pio 和 Cet 处理和未处理的 HT29-shE 细胞的 EMT 和 CSC 标记以及细胞形态。结果显示研究结果表明,浓度分别为 250 μM 和 40 μg/ml 的 Pio 和 Cet 能使细胞活力降低 50%。此外,它们还能减少富集了 CSC 的 HT29 细胞系中 CSC 标记(CD133 和 CD44)的表达。此外,Pio和Cet还能有效降低间质标志物波形蛋白的表达,并显著上调表皮标志物E-cadherin的表达。此外,经 Cet 处理后,HT29-shE 的间质形态转变为上皮形态。结论Pio和Cet可抑制EMT,减少EMT诱导/CSC富集细胞系的CSC标记物。我们希望,寻找类似这些药物的 EMT/CSC 靶向药物能对癌症治疗有所帮助。
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引用次数: 0
The Current Status and Future Direction of Extracellular Nano-vesicles in the Alleviation of Skin Disorders. 细胞外纳米微粒在缓解皮肤疾病方面的现状和未来方向。
IF 2.7 4区 医学 Q4 CELL & TISSUE ENGINEERING Pub Date : 2024-01-01 DOI: 10.2174/1574888X18666230418121053
Raziyeh Ghorbani, Simzar Hosseinzadeh, Arezo Azari, Niloofar Taghipour, Masoud Soleimani, Azam Rahimpour, Hojjat Allah Abbaszadeh

Exosomes are extracellular vesicles (EVs) that originate from endocytic membranes. The transfer of biomolecules and biological compounds such as enzymes, proteins, RNA, lipids, and cellular waste disposal through exosomes plays an essential function in cell-cell communication and regulation of pathological and physiological processes in skin disease. The skin is one of the vital organs that makes up about 8% of the total body mass. This organ consists of three layers, epidermis, dermis, and hypodermis that cover the outer surface of the body. Heterogeneity and endogeneity of exosomes is an advantage that distinguishes them from nanoparticles and liposomes and leads to their widespread usage in the remedy of dermal diseases. The biocompatible nature of these extracellular vesicles has attracted the attention of many health researchers. In this review article, we will first discuss the biogenesis of exosomes, their contents, separation methods, and the advantages and disadvantages of exosomes. Then we will highlight recent developments related to the therapeutic applications of exosomes in the treatment of common skin disorders like atopic dermatitis, alopecia, epidermolysis bullosa, keloid, melanoma, psoriasis, and systemic sclerosis.

外泌体是源自细胞内膜的细胞外囊泡 (EV)。生物大分子和生物化合物(如酶、蛋白质、RNA、脂质和细胞废物处理)通过外泌体转移,在细胞与细胞之间的交流以及调节皮肤病的病理和生理过程中发挥着重要功能。皮肤是人体的重要器官之一,约占人体总重量的 8%。该器官由表皮、真皮和皮下三层组成,覆盖身体外表面。外泌体的异质性和内源性是其有别于纳米颗粒和脂质体的优势,也是其广泛用于治疗皮肤疾病的原因。这些细胞外囊泡的生物相容性吸引了许多健康研究人员的关注。在这篇综述文章中,我们将首先讨论外泌体的生物生成、内容物、分离方法以及外泌体的优缺点。然后,我们将重点介绍外泌体在治疗特应性皮炎、脱发、表皮松解症、瘢痕疙瘩、黑色素瘤、银屑病和系统性硬化症等常见皮肤病方面的最新研究进展。
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引用次数: 0
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Current stem cell research & therapy
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