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Mesenchymal stem cells in neurological disorders: Insights from clinical trials 神经系统疾病中的间充质干细胞:来自临床试验的见解
IF 3.5 3区 环境科学与生态学 Q3 CELL & TISSUE ENGINEERING Pub Date : 2025-12-01 Epub Date: 2025-11-04 DOI: 10.1016/j.reth.2025.10.020
Beatriz Araújo , Inês Serrenho , Andreia Valente da Silva , Bragança Moisés Marceta , Graça Baltazar
Mesenchymal stem cells (MSCs) exhibit unique properties that make them promising candidates for cell therapy, particularly in neurological disorders. They can be derived from various tissues, with bone marrow, adipose tissue, umbilical cord, and placenta being the most common sources. Evidence suggests that the tissue of origin significantly influences MSC characteristics, including secretome composition, proliferation rate, and adhesion capacity.
Clinical trials have demonstrated the safety and therapeutic potential of MSCs in conditions such as spinal cord injury, multiple sclerosis, and stroke. MSC therapy has been associated with improvements in motor, sensory, and cognitive functions, as well as enhanced quality of life. Mechanistically, MSCs promote neuroprotection, reduce inflammation, and modulate immune responses. In spinal cord injury, intrathecal administration of adipose- and bone marrow-derived MSCs has led to significant functional recovery, with single high-dose treatments often yielding better outcomes than multiple lower doses. In amyotrophic lateral sclerosis, bone marrow-derived MSCs have shown potential in slowing disease progression, though higher doses do not always result in greater benefits. In multiple sclerosis, high doses of umbilical cord-derived MSCs improved quality of life and prevented disease progression, whereas lower doses of bone marrow-derived MSCs provided limited functional benefits.
While MSC therapy is considered safe, patient responses vary, and a definitive correlation between administered dose and therapeutic effects remains elusive. The small number of studies using comparable protocols impedes comparison of other relevant factor, limits the drawing of conclusions and underscore the importance of developing standardized protocols to optimize MSC-based treatments and maximize their clinical efficacy.
间充质干细胞(MSCs)表现出独特的特性,使其成为细胞治疗的有希望的候选者,特别是在神经系统疾病中。它们可以来自各种组织,骨髓、脂肪组织、脐带和胎盘是最常见的来源。有证据表明,来源组织显著影响间充质干细胞的特征,包括分泌组组成、增殖率和粘附能力。临床试验已经证明MSCs在脊髓损伤、多发性硬化症和中风等疾病中的安全性和治疗潜力。MSC治疗与运动、感觉和认知功能的改善以及生活质量的提高有关。在机制上,间充质干细胞促进神经保护,减少炎症,调节免疫反应。在脊髓损伤中,鞘内给予脂肪和骨髓来源的MSCs可显著恢复功能,单次高剂量治疗通常比多次低剂量治疗效果更好。在肌萎缩性侧索硬化症中,骨髓来源的MSCs显示出减缓疾病进展的潜力,尽管高剂量并不总是产生更大的益处。在多发性硬化症中,高剂量的脐带来源的MSCs改善了生活质量并预防了疾病进展,而低剂量的骨髓来源的MSCs提供了有限的功能益处。虽然骨髓间充质干细胞治疗被认为是安全的,但患者的反应各不相同,并且给药剂量和治疗效果之间的确切相关性仍然难以捉摸。使用可比较方案的研究数量较少,阻碍了其他相关因素的比较,限制了结论的得出,并强调了制定标准化方案以优化基于msc的治疗和最大化其临床疗效的重要性。
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引用次数: 0
Human iPSC-derived cerebral organoids reveal oxytocin-mediated protection against amyloid-β pathology 人类ipsc衍生的脑类器官显示催产素介导的对淀粉样蛋白-β病理的保护作用
IF 3.4 3区 环境科学与生态学 Q3 CELL & TISSUE ENGINEERING Pub Date : 2025-12-01 Epub Date: 2025-06-26 DOI: 10.1016/j.reth.2025.06.013
Tomoki Asaba, Sayuri Hamano, Ayaka Nanmo, Jieun Seo, Tatsuto Kageyama, Junji Fukuda

Introduction

Neuroinflammation is a key contributor to the pathogenesis of Alzheimer's disease (AD), and impaired clearance of amyloid-β (Aβ) by microglia is closely associated with disease progression. Oxytocin (OXT), a hypothalamic neuropeptide, has recently been reported to exert anti-inflammatory effects on microglia; however, its therapeutic potential in the human brain remains unclear.

Methods

We generated human cerebral organoids (hCOs) from induced pluripotent stem cells (iPSCs) to model early AD-like pathology. Aβ toxicity was induced by applying 3 μM Aβ1–42 for 48 h. The protective effects of OXT were evaluated through immunohistochemistry, RT-qPCR, calcium imaging, and multielectrode array (MEA) recordings. The involvement of microglia in Aβ clearance was assessed by immunostaining and gene expression analysis of TREM2.

Results

Aβ exposure led to significant deposition of Aβ in the outer layers of hCOs, accompanied by suppressed neural activity and increased apoptotic signaling. Pretreatment with OXT attenuated Aβ deposition and caspase-3-mediated apoptosis in a concentration-dependent manner. OXT also restored calcium oscillations and neuronal network activity as measured by MEA. Notably, OXT enhanced the recruitment of microglia to Aβ deposits and upregulated the expression of TREM2, a key regulator of microglial phagocytosis. Co-expression of oxytocin receptors (OXTR) on Iba1-positive microglia suggests that OXT directly modulates microglial activation and Aβ clearance.

Conclusions

OXT has neuroprotective effects on human cortical organoids by preserving their neuronal activity and promoting microglial-mediated Aβ clearance. This study provides novel insights into the therapeutic potential of OXT for targeting neuroinflammation and Aβ pathology in patients with AD.
神经炎症是阿尔茨海默病(AD)发病的关键因素,小胶质细胞对淀粉样蛋白-β (a β)的清除受损与疾病进展密切相关。催产素(OXT)是一种下丘脑神经肽,最近被报道对小胶质细胞具有抗炎作用;然而,它在人脑中的治疗潜力尚不清楚。方法利用诱导多能干细胞(iPSCs)生成人脑类器官(hCOs),模拟早期ad样病理。3 μM a - β1 - 42作用48 h诱导Aβ毒性,通过免疫组织化学、RT-qPCR、钙显像和多电极阵列(MEA)记录评价OXT的保护作用。通过免疫染色和TREM2基因表达分析评估小胶质细胞在Aβ清除中的作用。结果sa β暴露导致hCOs外层Aβ显著沉积,并伴有神经活性抑制和凋亡信号通路增加。OXT预处理以浓度依赖的方式减弱a β沉积和caspase-3介导的细胞凋亡。经MEA测量,OXT还能恢复钙振荡和神经网络活动。值得注意的是,OXT增强了小胶质细胞对a β沉积物的募集,并上调了TREM2的表达,TREM2是小胶质细胞吞噬的关键调节因子。催产素受体(OXTR)在iba1阳性小胶质细胞上的共表达表明,OXT直接调节小胶质细胞的激活和Aβ清除。结论soxt对人皮质类器官具有神经保护作用,其机制是维持类器官的神经元活性,促进小胶质介导的Aβ清除。这项研究为OXT靶向AD患者的神经炎症和Aβ病理的治疗潜力提供了新的见解。
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引用次数: 0
From an Antimicrobial Agent to a constituent of 3D Printed Heterogenous Scaffolds Stimulating Bone Characteristics: An In-vitro and Animal model evaluation 从抗菌剂到3D打印异质支架刺激骨特性的成分:体外和动物模型评估
IF 3.5 3区 环境科学与生态学 Q3 CELL & TISSUE ENGINEERING Pub Date : 2025-12-01 Epub Date: 2025-08-12 DOI: 10.1016/j.reth.2025.08.001
Shahad Ahmed Daood , Martha Then Xin Yi , Nicole Wen Ce Mun , Sharjeel Ilyas , Lee Yin Shien , Oh Jia En , Syed Saad Bin Qasim , Yichen Dai , Galvinderjeet Kaur Grewal , Ng Mei Liit , Gopu Sriram , Malikarjuna Rao Pichika , Kit-Kay Mak , Ranjeet Ajit Bapat , Zeeshan Sheikh , Umer Daood
This paper describes a promising candidate molecule, investigates the pattern of scaffold composition which arises and assesses the effect of the agent on its mechanical properties.

Methods

Scaffold samples were fabricated using a commercial extrusion bioprinter equipped with a pneumatic printhead fitted with a 21G conical nozzle. The Pore Printability Index, and the area and perimeter of the pore within the grid patterns were quantified using ImageJ software (NIH, USA). Mechanical properties of scaffolds were assessed using atomic force microscopy. The phase composition and crystal structures were analyzed using X-ray diffraction and Raman mapping. Morphologies of human gingival fibroblastic cells were examined using scanning electron microscopy. Lactobacillus biofilms were generated for cytolysin peptide cleavage. A rabbit bone defect model with scaffold implantations was used to provide histologic specimens for measuring percentages of bone trabeculae, collagen fibers and inflammatory cells along with granulation tissue. The Primeway Total RNA Extraction Kit was used for RNA extraction.

Results

All bioink formulations demonstrated successful printing of 3D grid and solid square patterned scaffolds achieving Pr values exceeding 0.9. 0.1 %K21 group showed the highest elastic modulus. XRD revealed a pattern producing around 90 % β-tricalcium phosphate displaying two peaks at 2θ angles. 0.1 % K21 and 0.1 %CHX did not alter scaffold's pore size and porosity. 0.1 %K21 group exhibited highest ratio (62.5 ± 6.1 θ), significantly surpassing control. Surface morphologies of cells were also well retained. TEM image shows a sequence of structural changes in fibroblastic cell structure when exposed to K21. 0.1 % K21 proved to be critical in completely eradicating the biofilm. 0.K21 group closed the openings of wound areas completely. Correlation coefficient of gene expression levels demonstrates sample variations and recurring instances among groupings.

Conclusion

3D-printing technologies with 0.1 %K21 represent a significant advancement over conventional regenerative medicine techniques for bone-related treatments.
本文描述了一个有前途的候选分子,研究了支架组成的模式,并评估了该剂对其力学性能的影响。方法采用商用挤压生物打印机制备支架样品,该打印机配备21G锥形喷嘴的气动打印头。使用ImageJ软件(NIH, USA)对孔隙可打印性指数以及网格模式内孔隙的面积和周长进行量化。采用原子力显微镜观察支架的力学性能。利用x射线衍射和拉曼图分析了相组成和晶体结构。用扫描电镜观察了人牙龈成纤维细胞的形态。制备乳酸菌生物膜裂解细胞溶素肽。采用支架植入兔骨缺损模型提供组织学标本,测定骨小梁、胶原纤维、炎性细胞及肉芽组织的百分比。采用Primeway总RNA提取试剂盒进行RNA提取。结果所有生物墨水配方均成功打印出三维网格和实心方形支架,Pr值均超过0.9。0.1% K21组弹性模量最高。XRD谱图显示,β-磷酸三钙含量约为90%,在2θ角处有两个峰。0.1%的K21和0.1%的CHX没有改变支架的孔径和孔隙率。0.1% K21组比例最高(62.5±6.1 θ),显著高于对照组。细胞的表面形态也保留得很好。TEM图像显示了暴露于K21时成纤维细胞结构的一系列结构变化。0.1%的K21被证明是完全根除生物膜的关键。0.K21组完全闭合创面开口。基因表达水平的相关系数显示了样本差异和组间反复出现的情况。结论添加0.1% K21的3d打印技术在骨相关治疗方面是传统再生医学技术的重大进步。
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引用次数: 0
Nanosecond pulsed electric field applications rejuvenate aging endothelial cells by rescuing mitochondrial-to-nuclear retrograde communication 纳秒脉冲电场应用通过挽救线粒体到核的逆行通讯使老化的内皮细胞恢复活力
IF 3.4 3区 环境科学与生态学 Q3 CELL & TISSUE ENGINEERING Pub Date : 2025-12-01 Epub Date: 2025-06-18 DOI: 10.1016/j.reth.2025.06.004
Meifang Yin , Jie Xiao , Guangtao Huang , Huanyu Xie , Hongwei Liu , Jianqiang Yuan , Xiaofang Liu , Anna Chiarini , Ubaldo Armato , Ilaria Dal Prà , Shumaila Ijaz , Naziat Begum , Lingyun Wang , Jun Wu

Introduction

Endothelial cell aging is strongly associated with mitochondrial dysfunction, particularly the disruption of mitochondrial-nuclear retrograde communication (MNRC), which is essential for sustaining cellular homeostasis and regulating crucial cellular processes. Nanosecond pulsed electric fields (nsPEF) were shown to exert biological effects by targeting mitochondria. However, the nsPEF regulation of MNRC is still unclear.

Methods

In this study, we set up an in vitro model of d-galactose-induced senescence in human umbilical vein endothelial cells (HUVECs) to investigate the effects of nsPEF treatment on oxidative stress, cell proliferation, mitochondrial membrane potential, and markers of MNRC (MNRC), including HIF-1α and SIRT1. Moreover, we conducted in vivo animal experiments to evaluate nsPEF treatment's effects on HIF-1α and SIRT1 protein expression in endothelial cells (ECs) of in vivo rodents' aging/senescing skin tissue, as well as to examine any later changes in vascular density within the skin.

Results

In vitro results showed that nsPEF treatment suppressed d-galactose-induced senescing effects as they rescued mitochondrial membrane potential, and activated HIF-1α and SIRT1. These effects were confirmed by concurrent reductions in SA-β-Gal activity and in ROS production, and increases in EdU-positive (DNA-synthesizing) cells. Our data showed that nsPEF treatments rescued endothelial cells from d-galactose senescence. Interestingly, nsPEF selectively targeted senescing cells at the tested dose, with no detectable effect on otherwise untreated (normal) HUVECs. In vivo nsPEF treatments upregulated the expression of HIF-1α and SIRT1 in ECs and promoted neoangiogenesis in aged/senescent rodents' skin.

Conclusions

These findings suggest that nsPEF treatments rescue ECs from aging by restoring MNRC, highlighting its potential as a therapeutic strategy for age-related vascular diseases.
内皮细胞衰老与线粒体功能障碍密切相关,尤其是线粒体-核逆行通讯(MNRC)的中断,而线粒体-核逆行通讯对于维持细胞稳态和调节关键细胞过程至关重要。纳秒脉冲电场(nsPEF)通过靶向线粒体发挥生物学效应。然而,MNRC对nsPEF的监管仍不明确。方法建立d-半乳糖诱导的人脐静脉内皮细胞(HUVECs)体外衰老模型,研究nsPEF处理对氧化应激、细胞增殖、线粒体膜电位及MNRC (MNRC)标志物HIF-1α和SIRT1的影响。此外,我们进行了体内动物实验,以评估nsPEF处理对体内啮齿动物老化/衰老皮肤组织内皮细胞(ECs)中HIF-1α和SIRT1蛋白表达的影响,并检查皮肤内血管密度的任何后续变化。结果体外实验结果显示,nsPEF通过挽救线粒体膜电位,激活HIF-1α和SIRT1,抑制了d-半乳糖诱导的衰老效应。SA-β-Gal活性和ROS生成同时降低,edu阳性(dna合成)细胞增加,证实了这些影响。我们的数据显示,nsPEF治疗可使内皮细胞免于d-半乳糖衰老。有趣的是,在测试剂量下,nsPEF选择性地靶向衰老细胞,对未处理(正常)的HUVECs没有可检测到的影响。体内nsPEF处理上调ECs中HIF-1α和SIRT1的表达,促进老年/衰老啮齿动物皮肤新生血管生成。这些发现表明,nsPEF治疗通过恢复MNRC来拯救内皮细胞免于衰老,突出了其作为年龄相关血管疾病治疗策略的潜力。
{"title":"Nanosecond pulsed electric field applications rejuvenate aging endothelial cells by rescuing mitochondrial-to-nuclear retrograde communication","authors":"Meifang Yin ,&nbsp;Jie Xiao ,&nbsp;Guangtao Huang ,&nbsp;Huanyu Xie ,&nbsp;Hongwei Liu ,&nbsp;Jianqiang Yuan ,&nbsp;Xiaofang Liu ,&nbsp;Anna Chiarini ,&nbsp;Ubaldo Armato ,&nbsp;Ilaria Dal Prà ,&nbsp;Shumaila Ijaz ,&nbsp;Naziat Begum ,&nbsp;Lingyun Wang ,&nbsp;Jun Wu","doi":"10.1016/j.reth.2025.06.004","DOIUrl":"10.1016/j.reth.2025.06.004","url":null,"abstract":"<div><h3>Introduction</h3><div>Endothelial cell aging is strongly associated with mitochondrial dysfunction, particularly the disruption of mitochondrial-nuclear retrograde communication (MNRC), which is essential for sustaining cellular homeostasis and regulating crucial cellular processes. Nanosecond pulsed electric fields (nsPEF) were shown to exert biological effects by targeting mitochondria. However, the nsPEF regulation of MNRC is still unclear.</div></div><div><h3>Methods</h3><div>In this study, we set up an <em>in vitro</em> model of <span>d</span>-galactose-induced senescence in human umbilical vein endothelial cells (HUVECs) to investigate the effects of nsPEF treatment on oxidative stress, cell proliferation, mitochondrial membrane potential, and markers of MNRC (MNRC), including HIF-1α and SIRT1. Moreover, we conducted <em>in vivo</em> animal experiments to evaluate nsPEF treatment's effects on HIF-1α and SIRT1 protein expression in endothelial cells (ECs) of <em>in vivo</em> rodents' aging/senescing skin tissue, as well as to examine any later changes in vascular density within the skin.</div></div><div><h3>Results</h3><div>In vitro results showed that nsPEF treatment suppressed <span>d</span>-galactose-induced senescing effects as they rescued mitochondrial membrane potential, and activated HIF-1α and SIRT1. These effects were confirmed by concurrent reductions in SA-β-Gal activity and in ROS production, and increases in EdU-positive (DNA-synthesizing) cells. Our data showed that nsPEF treatments rescued endothelial cells from <span>d</span>-galactose senescence. Interestingly, nsPEF selectively targeted senescing cells at the tested dose, with no detectable effect on otherwise untreated (normal) HUVECs. In vivo nsPEF treatments upregulated the expression of HIF-1α and SIRT1 in ECs and promoted neoangiogenesis in aged/senescent rodents' skin.</div></div><div><h3>Conclusions</h3><div>These findings suggest that nsPEF treatments rescue ECs from aging by restoring MNRC, highlighting its potential as a therapeutic strategy for age-related vascular diseases.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 207-216"},"PeriodicalIF":3.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144307633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Current challenges and future directions of ATMPs in regenerative medicine ATMPs在再生医学中的当前挑战和未来方向
IF 3.4 3区 环境科学与生态学 Q3 CELL & TISSUE ENGINEERING Pub Date : 2025-12-01 Epub Date: 2025-07-09 DOI: 10.1016/j.reth.2025.06.017
Fatemeh Abbasi Kakroodi , Elaheh Khodadoust , Marzieh Alizadeh , Reyhaneh Sadat Hayaei Tehrani , Pedram Asadi Sarabi , Mohammad Rahmanian , Massoud Vosough
Advanced therapy medicinal products (ATMPs) represent a groundbreaking category of medications that utilize biological-based products to treat or replace damaged organs. It offers potential solutions for complex diseases through gene therapy, somatic cell therapy, tissue engineering, and combined therapies. Although ATMPs have offered significant improvement for a variety of severe illnesses, their progressive development is faced with numerous challenges. Some of these challenges are current complexities in their manufacturing, such as scaling up, scaling out, product efficacy, packaging, storage, stability, and logistic concerns. Other challenges include manufacturing, efficacy, and scaling up of ATMPs, as well as establishing Good Manufacturing Practice (GMP)-compliant processes that align with product specifications derived from non-clinical studies conducted under Good Laboratory Practice (GLP). Additionally, safety concerns such as tumorigenesis are potential. Regulatory and ethical concerns, along with the need for standardization and clear clinical guidelines, are also critical obstacles. To address these challenges, novel technologies such as organoids, artificial intelligence, dynamic culture systems, and biobanking are being explored, providing new opportunities to enhance the consistency, scalability, and precision of ATMP production. Development in artificial intelligence (AI) technology helped scientists to address monitoring concerns, automation, and data management. Introducing advanced guidelines in biobanking helps researchers to overcome the storage and stability concerns. Organoid technology holds a significant promise in overcoming the challenges associated with preclinical and modeling of ATMPs by providing more accurate models for diseases, drug screening, and personalized medicine. This article reviews the current challenges in ATMP manufacturing and application, highlights the advancements in technology that are paving the way for improved therapeutic strategies, and offers future perspectives on overcoming these barriers.
先进治疗药物产品(ATMPs)是一类突破性的药物,它利用生物为基础的产品来治疗或替代受损器官。它通过基因治疗、体细胞治疗、组织工程和联合治疗为复杂疾病提供了潜在的解决方案。尽管atmp对多种严重疾病有显著的改善作用,但其逐步发展面临着许多挑战。其中一些挑战是当前制造中的复杂性,例如扩大规模、扩大规模、产品功效、包装、存储、稳定性和物流问题。其他挑战包括atmp的生产、疗效和扩大规模,以及建立符合良好生产规范(GMP)的流程,该流程与根据良好实验室规范(GLP)进行的非临床研究得出的产品规格保持一致。此外,安全问题,如肿瘤发生是潜在的。监管和伦理问题,以及对标准化和明确临床指南的需要,也是关键障碍。为了应对这些挑战,人们正在探索诸如类器官、人工智能、动态培养系统和生物银行等新技术,为提高ATMP生产的一致性、可扩展性和精度提供了新的机会。人工智能(AI)技术的发展帮助科学家解决了监测问题、自动化和数据管理。引入先进的生物银行指南有助于研究人员克服储存和稳定性问题。通过为疾病、药物筛选和个性化医疗提供更准确的模型,类器官技术在克服与atmp临床前和建模相关的挑战方面具有重要的前景。本文回顾了目前在ATMP制造和应用方面面临的挑战,强调了为改进治疗策略铺平道路的技术进步,并提供了克服这些障碍的未来前景。
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引用次数: 0
Ex vivo expansion of corneal endothelial cells enabled by small molecule inhibitors of LATS kinase LATS激酶小分子抑制剂使角膜内皮细胞体外扩增
IF 3.5 3区 环境科学与生态学 Q3 CELL & TISSUE ENGINEERING Pub Date : 2025-12-01 Epub Date: 2025-09-03 DOI: 10.1016/j.reth.2025.08.014
Natsuki Abe-Fukasawa , Ryuhei Hayashi , Mio Morita , Shohei Azuma , Takumi Iwawaki , Kenta Kagaya , Taito Nishino , Kohji Nishida

Introduction

Transplantation of expanded corneal endothelial cells (CECs) has been regarded as a promising approach for treating corneal diseases caused by CEC damage or dysfunction. However, an efficient method for expanding CECs remains inadequately established.

Methods

We examined whether small molecule inhibitors of large tumor suppressor kinase (LATS) promote the proliferation of CECs. We also evaluated the expression of functional markers in CECs treated with the inhibitors.

Results

We found that LATS kinase inhibitors enhance the cell density of bovine CECs ex vivo. CECs that were expanded in the presence of these inhibitors exhibited increased nuclear translocation of yes-associated protein (YAP) and upregulated expression of YAP-regulated genes. Furthermore, we observed that YAP was essential for promoting cell proliferation. Notably, the inhibitors also increased the density of primary human CECs. Expanded human CECs expressed CEC functional markers, including Na+/K+-transporting ATPase subunit alpha-1 (ATP1A1), Zonula occludens-1 (ZO-1), and N-cadherin; they showed upregulated expression of YAP-regulated genes.

Conclusions

Collectively, these findings support the development of efficient culture techniques for CEC expansion and may facilitate the advancement of therapeutic strategies for CEC-associated diseases.
扩大的角膜内皮细胞(CECs)移植被认为是治疗由CEC损伤或功能障碍引起的角膜疾病的一种很有前途的方法。然而,扩大cec的有效方法仍未充分确立。方法观察大肿瘤抑制激酶(large tumor suppressor kinase, LATS)小分子抑制剂是否促进CECs增殖。我们还评估了用抑制剂治疗的CECs中功能标志物的表达。结果LATS激酶抑制剂可提高体外牛CECs细胞密度。在这些抑制剂存在的情况下,cec的扩增表现出yes相关蛋白(YAP)的核易位增加和YAP调控基因的表达上调。此外,我们观察到YAP对促进细胞增殖至关重要。值得注意的是,抑制剂也增加了原发人CECs的密度。扩增的人CEC表达CEC功能标记物,包括Na+/K+转运atp酶亚基α -1 (ATP1A1)、封闭带-1 (ZO-1)和n -钙粘蛋白;它们表现出yap调控基因的上调表达。综上所述,这些发现支持了CEC扩展的高效培养技术的发展,并可能促进CEC相关疾病的治疗策略的发展。
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引用次数: 0
Preface of the special issue “Mechanisms of reprogramming for cell differentiation and tissue regeneration” 《细胞分化与组织再生的重编程机制》专刊前言
IF 3.4 3区 环境科学与生态学 Q3 CELL & TISSUE ENGINEERING Pub Date : 2025-12-01 Epub Date: 2025-05-16 DOI: 10.1016/j.reth.2025.05.005
Goshi Shiota (Senior Associate Editor)
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引用次数: 0
Optimized personnel flow with minimal contamination: development and validation of an air-barrier cleanroom for cell products processing 以最小的污染优化人员流动:开发和验证用于细胞产品处理的空气屏障洁净室
IF 3.5 3区 环境科学与生态学 Q3 CELL & TISSUE ENGINEERING Pub Date : 2025-12-01 Epub Date: 2025-09-18 DOI: 10.1016/j.reth.2025.09.001
Mitsuru Mizuno , Hideaki Tani , Kaori Nomura , Daijiro Sone , Kentaro Amano , Gen Tominaga , Yuki Chiba , Ichiro Sekiya

Introduction

Cell processing facilities for regenerative medicine require strict prevention of cross-contamination. However, the typically employed sealed, multi-room layout increases energy demands and capital costs due to heating, ventilation, and air-conditioning (HVAC), and restricts staff mobility. We devised a semi-open (SO) cleanroom that eliminated doors between the cell processing room (CPR) and adjoining corridor, while maintaining unidirectional airflow as a barrier. This study rigorously compared four interface variants—plain opening, wing walls, push–pull ventilation, and a conventional swing door—to verify whether operational flexibility can be achieved without compromising particle content performance at the CPR–corridor interface.

Methods

Computational fluid dynamics (CFD) simulations reproduced two connected rooms separated by a 900 × 2000-mm2 opening, supplied at 23 m3/min (35 air changes per hour) constantly. Four interfaces were evaluated: plain opening, 100–500 mm wing-wall panels, push–pull ventilation adjusted to a 0.75 ratio, and a conventional swing door. A 1-m/s cross-draft emulated personnel transit. Identical full-scale mock-ups were built; particle image velocimetry (PIV) quantified airflow vectors, and optical counters logged 0.5-μm aerosols during 5-min exit and entry. The primary endpoints were the inflow particle concentration ratio across the opening and the cumulative adjacent-room transfer proportions.

Results

CFD showed all layouts leaked ≤0.011 %, with a 1 m/s walking draft, push–pull kept inflow below 0.05 %, halving 500-mm wing-wall performance and outperforming plain openings. The PIV confirmed significant differences in airflow velocity distributions under each condition in the case of the exit. The semi-open layout without doors showed a lower proportion of vectors pointing opposite to the forward direction than the conventional layout in both the exit and entry cases. Particle counts supported this: push–pull transferred 0.013 % of particles on exit, 32.8 % on entry, giving overall migration to the adjacent room of 0.0043 %.

Conclusions

The SO cleanroom concept suppresses fluctuations in particle content at the CPR–corridor interface while eliminating physical doors, enabling flexible personnel flow and obviating extra HVAC zones. Push–pull ventilation delivered the most robust containment against walking-induced disturbances, whereas the 500-mm wing walls offered a passive, power-free alternative with moderate protection. With worst-case inter-room transfers below 0.05 %, SO designs can rationally replace conventional door-sealed rooms, substantially reducing energy and construction costs in regenerative medicine manufacturing.
再生医学的细胞处理设施需要严格防止交叉污染。然而,由于采暖、通风和空调(HVAC),通常采用密封的多房间布局增加了能源需求和资本成本,并限制了员工的流动性。我们设计了一个半开放式(SO)洁净室,消除了细胞处理室(CPR)和相邻走廊之间的门,同时保持单向气流作为屏障。本研究严格比较了四种不同的界面——平开口、翼墙、推拉式通风和传统的旋转门,以验证在不影响cpr -走廊界面颗粒含量性能的情况下,是否可以实现操作灵活性。方法计算流体力学(CFD)模拟再现了两个相连的房间,由一个900 × 2000-mm2的开口隔开,以23 m3/min(每小时换气35次)的速度连续供气。评估了四个界面:普通开口,100-500毫米翼墙面板,推拉通风调节到0.75比率,以及传统的旋转门。1米/秒的交叉通风模拟人员运输。制作了完全相同的全尺寸模型;粒子图像测速(PIV)量化了气流矢量,光学计数器记录了0.5 μm气溶胶在5分钟内的进出情况。主要终点是入口颗粒浓度比和累积的相邻室转移比。结果scfd显示,所有布局漏损≤0.011%,行走吃水1 m/s,推挽流保持在0.05%以下,500 mm翼壁性能降低一半,优于普通开孔。PIV证实,在出口情况下,各工况下的气流速度分布存在显著差异。在出入口两种情况下,无门的半开放式布局中指向前方相反方向的矢量所占比例均低于常规布局。粒子计数支持这一点:推拉在出口转移了0.013%的粒子,在入口转移了32.8%,总体迁移到相邻房间的比例为0.0043%。SO洁净室概念抑制了cpr -走廊界面颗粒含量的波动,同时消除了物理门,实现了灵活的人员流动,避免了额外的暖通空调区域。推挽式通风系统对行走引起的干扰提供了最强大的遏制,而500毫米的翼墙则提供了一种被动的、无动力的替代方案,具有适度的保护作用。SO设计可合理替代传统的闭门房间,在最坏情况下房间间传输量低于0.05%,大大降低再生医药制造的能源和建筑成本。
{"title":"Optimized personnel flow with minimal contamination: development and validation of an air-barrier cleanroom for cell products processing","authors":"Mitsuru Mizuno ,&nbsp;Hideaki Tani ,&nbsp;Kaori Nomura ,&nbsp;Daijiro Sone ,&nbsp;Kentaro Amano ,&nbsp;Gen Tominaga ,&nbsp;Yuki Chiba ,&nbsp;Ichiro Sekiya","doi":"10.1016/j.reth.2025.09.001","DOIUrl":"10.1016/j.reth.2025.09.001","url":null,"abstract":"<div><h3>Introduction</h3><div>Cell processing facilities for regenerative medicine require strict prevention of cross-contamination. However, the typically employed sealed, multi-room layout increases energy demands and capital costs due to heating, ventilation, and air-conditioning (HVAC), and restricts staff mobility. We devised a semi-open (SO) cleanroom that eliminated doors between the cell processing room (CPR) and adjoining corridor, while maintaining unidirectional airflow as a barrier. This study rigorously compared four interface variants—plain opening, wing walls, push–pull ventilation, and a conventional swing door—to verify whether operational flexibility can be achieved without compromising particle content performance at the CPR–corridor interface.</div></div><div><h3>Methods</h3><div>Computational fluid dynamics (CFD) simulations reproduced two connected rooms separated by a 900 × 2000-mm<sup>2</sup> opening, supplied at 23 m<sup>3</sup>/min (35 air changes per hour) constantly. Four interfaces were evaluated: plain opening, 100–500 mm wing-wall panels, push–pull ventilation adjusted to a 0.75 ratio, and a conventional swing door. A 1-m/s cross-draft emulated personnel transit. Identical full-scale mock-ups were built; particle image velocimetry (PIV) quantified airflow vectors, and optical counters logged 0.5-μm aerosols during 5-min exit and entry. The primary endpoints were the inflow particle concentration ratio across the opening and the cumulative adjacent-room transfer proportions.</div></div><div><h3>Results</h3><div>CFD showed all layouts leaked ≤0.011 %, with a 1 m/s walking draft, push–pull kept inflow below 0.05 %, halving 500-mm wing-wall performance and outperforming plain openings. The PIV confirmed significant differences in airflow velocity distributions under each condition in the case of the exit. The semi-open layout without doors showed a lower proportion of vectors pointing opposite to the forward direction than the conventional layout in both the exit and entry cases. Particle counts supported this: push–pull transferred 0.013 % of particles on exit, 32.8 % on entry, giving overall migration to the adjacent room of 0.0043 %.</div></div><div><h3>Conclusions</h3><div>The SO cleanroom concept suppresses fluctuations in particle content at the CPR–corridor interface while eliminating physical doors, enabling flexible personnel flow and obviating extra HVAC zones. Push–pull ventilation delivered the most robust containment against walking-induced disturbances, whereas the 500-mm wing walls offered a passive, power-free alternative with moderate protection. With worst-case inter-room transfers below 0.05 %, SO designs can rationally replace conventional door-sealed rooms, substantially reducing energy and construction costs in regenerative medicine manufacturing.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 760-768"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145094918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Mid-term outcomes of a bio-artificial pleura composed of autologous dermal fibroblasts used to close intraoperative pulmonary air leaks caused by intraoperative pleural injury: A case report 由自体真皮成纤维细胞组成的生物人工胸膜用于术中胸膜损伤引起的肺气漏的中期结果:1例报告
IF 3.4 3区 环境科学与生态学 Q3 CELL & TISSUE ENGINEERING Pub Date : 2025-12-01 Epub Date: 2025-06-23 DOI: 10.1016/j.reth.2025.06.001
Masato Kanzaki , Ryo Takagi , Shota Mitsuboshi , Tamami Isaka , Masayuki Yamato

Introduction

The visceral pleura is a thin, serous membrane that closely covers the surface of the lung. The pleura is injured or ruptured, causing air to accumulate in the thoracic cavity and the lung to collapse. Increased pleural pressure due to lung air leaks (LALs) from the lung can have serious effects. LALs are frequently observed due to pleural injury caused by lung resection. Postoperative LALs prolongs hospital stay and has a significant impact on patients' postoperative quality of life. Based on the above background, we developed and reported the effectiveness of dermal fibroblast sheet (DFS) as a bio-artificial pleura for closing LALs caused by intraoperative pleural injury in humans for the first time in a clinical study. There are no mid-term reports of bio-artificial pleura created using tissue engineering. In this study, we report the safety of bio-artificial pleural transplantation using cultured autologous DFS for pleural injury in two cases.

Previous study and case presentation

Two of the five patients who met the criteria and underwent LAL closure using a bio-artificial pleura between May 2016 and March 2018 were followed up mid-term. Although the criteria included a 6-month monitoring period after LAL closure, these two patients continued to visit our hospital beyond the monitoring period for treatment of other comorbid conditions. Case 1. A male in his 40s who was receiving long-term steroid therapy for Takayasu's disease and underwent thoracoscopic lung wedge resection for a benign lung tumor in the left anteromedial basal segment. During surgery, the minor LALs from the resection margins with an automatic stapler were closed with a bio-artificial pleura, specifically, a total of three DFSs. During the patient's 51-month follow-up, no LAL recurrence, tumor development, infiltration, and fibrogenesis were observed. Case 2. A female patient in her 70s had bullae associated with combined pulmonary fibrosis and emphysema (CPFE). Thoracoscopic bullectomy of the left lower lobe was performed, and the major LALs were closed intraoperatively with a bio-artificial pleura consisting of a total of eight DFSs. She was readmitted for contralateral pneumonia 2 months after surgery. During a follow-up period of 82 months, no LAL recurrence and tumor development was observed in the operated left lung. However, chest CT revealed slowly progressing CPFE lesions.

Conclusions

This report of two cases demonstrated the mid-term safety of bio-artificial pleural transplantation using cultured autologous DFS for pleural injury.
内脏胸膜是一层薄的浆膜,紧密地覆盖在肺表面。胸膜受伤或破裂,导致空气在胸腔中积聚,肺部塌陷。由于肺部漏气(LALs)引起的胸膜压力增加会产生严重的影响。肺切除术引起的胸膜损伤是LALs的常见原因。术后LALs延长了患者住院时间,对患者术后生活质量有显著影响。基于上述背景,我们首次在临床研究中开发并报道了真皮成纤维细胞片(真皮成纤维细胞片,真皮成纤维细胞片)作为生物人工胸膜用于闭合人类术中胸膜损伤引起的LALs的有效性。目前还没有利用组织工程技术制造生物人工胸膜的中期报道。在本研究中,我们报告了用培养的自体DFS生物人工胸膜移植治疗两例胸膜损伤的安全性。2016年5月至2018年3月期间,5例符合标准并使用生物人工胸膜闭合LAL的患者中有2例进行了中期随访。虽然标准包括LAL关闭后6个月的监测期,但这两名患者在监测期后继续来我院治疗其他合并症。案例1。男性,40多岁,因Takayasu病接受长期类固醇治疗,因左前内侧基底段良性肺肿瘤行胸腔镜肺楔形切除术。手术中,使用自动吻合器将切除边缘的小LALs用生物人工胸膜闭合,具体来说,总共有3个dfs。在患者51个月的随访中,未见LAL复发、肿瘤发展、浸润和纤维形成。例2。一位70多岁的女性患者有大泡合并肺纤维化和肺气肿(CPFE)。胸腔镜下行左下叶大泡切除术,术中用共8个dfs组成的生物人工胸膜封闭主要LALs。术后2个月因对侧肺炎再次入院。随访82个月,术后左肺未见LAL复发及肿瘤发展。然而,胸部CT显示进展缓慢的CPFE病变。结论2例胸膜损伤采用培养的自体DFS进行生物人工胸膜移植具有中期安全性。
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引用次数: 0
A bibliometric analysis of the global status of platelet-rich plasma in regenerative medicine from 2004 to 2023 2004年至2023年全球富血小板血浆再生医学现状的文献计量学分析
IF 3.5 3区 环境科学与生态学 Q3 CELL & TISSUE ENGINEERING Pub Date : 2025-12-01 Epub Date: 2025-07-29 DOI: 10.1016/j.reth.2025.07.007
Siwen Zhang , Xudong Zhang , Haochen Zhang , Shengqing Zhang , Zichen Liu , Shanshan Wu , Yimeng Lu , Chao Han , Jichun Tan

Introduction

Platelet-rich plasma (PRP) is a plasma product that concentrates platelets from whole blood and used widely in regenerative medicine. This study aimed to evaluate the evolution, development trend, and research highlights of research status of PRP in regenerative medicine.

Methods

Publications related to PRP were retrieved from the Science Citation Index Expanded (SCIE) database of the Web of Science (WoS) in February 2024. The impact factor (IF) was used to evaluate and compare the contributions of different countries. Then, the top 10 countries, top 10 productive journals, top 10 WoS categories, and top 10 most cited articles were listed. The data was processed, and the relative contributions of the top 10 productive countries in each year were presented in a line chart and a heatmap. VOSviewer software and heatmap were used to investigate the holistic trend of research highlights according to the change trends of keywords.

Results

A total of 9,577 publications were retrieved from SCIE database. The USA topped the list with 2,311 papers, followed by China (1,583 papers), the UK (525 papers), and Spain (512 papers). The studies of PRP in regenerative medicine have increasing trend globally. The USA had the most total citation and took the leading position for relative contributions, the UK ranked 1st in average citations and average IF. However, China's contribution had a dramatically increasing trend since 2015, and exceeded the USA in 2022. There were seven keywords of “Bone-related cluster”, “hyaluronic acid-related cluster”, “cartilage-related cluster”, “stomatology-related cluster”, “damage repair-related cluster”, “experiment-related cluster”, and “nerve-related cluster” generated in keyword co-occurrence analysis. Except for bone & joint diseases, novel clinical applications of PRP have been carried out, including dental and neurological practice, reproductive medicine, dermatology, gynecology, and plastic surgery, cosmetic treatments, and the improvement of non-musculoskeletal organ function.

Conclusion

To summarize, the research advancements of PRP appear to be more prominent in the United States and China. Experimental research on PRP is mostly concentrated on exploring on mechanism and signal pathway. As an effective adjuvant treatment, the clinical application of PRP has expanded from initial trauma repair to multiple systemic organ disorders. Leveraging the intersection of multiple disciplines, the development of novel PRP-based medical materials tailored to specific disease characteristics may represent a promising direction for future research.
富血小板血浆(PRP)是一种浓缩全血血小板的血浆产品,广泛用于再生医学。本研究旨在评价PRP在再生医学研究现状的演变、发展趋势和研究重点。方法从Web of Science (WoS)的SCIE数据库中检索2024年2月与PRP相关的出版物。影响因子(IF)被用来评价和比较不同国家的贡献。然后,列出了排名前10的国家、排名前10的高产期刊、排名前10的WoS类别和排名前10的被引文章。对数据进行了处理,并以折线图和热图的形式展示了每年产量最高的10个国家的相对贡献。根据关键词的变化趋势,利用VOSviewer软件和热图对研究亮点进行整体趋势调查。结果SCIE数据库共检索文献9577篇。美国以2311篇论文位居榜首,其次是中国(1583篇)、英国(525篇)、西班牙(512篇)。PRP在再生医学领域的研究在全球范围内呈增长趋势。美国的总被引次数最多,相对贡献排名第一,英国的平均被引次数和平均影响因子排名第一。但自2015年以来,中国的贡献呈急剧上升趋势,并在2022年超过了美国。关键词共现分析共生成“骨相关类”、“透明质酸相关类”、“软骨相关类”、“口腔相关类”、“损伤修复相关类”、“实验相关类”、“神经相关类”7个关键词。除了骨头&;在关节疾病方面,PRP的新临床应用已经开展,包括牙科和神经医学、生殖医学、皮肤科、妇科、整形外科、美容治疗以及非肌肉骨骼器官功能的改善。综上所述,PRP在美国和中国的研究进展较为突出。PRP的实验研究多集中在机理和信号通路的探索上。作为一种有效的辅助治疗,PRP的临床应用已经从最初的创伤修复扩展到多系统器官疾病。利用多学科交叉,开发针对特定疾病特征的新型prp医疗材料可能是未来研究的一个有希望的方向。
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引用次数: 0
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Regenerative Therapy
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