Engineered regeneration最新文献_第2页

Corrigendum to ‘LSM6 promotes cell proliferation and migration regulated by HMGB1 in laryngeal squamous cell carcinoma’[Engineered Regeneration 5 (2024) 247-254] “喉鳞癌中LSM6促进HMGB1调控的细胞增殖和迁移”的更正[工程再生5 (2024)247-254]

Q1 Medicine

Engineered regeneration

Pub Date : 2025-01-01 DOI: 10.1016/j.engreg.2025.12.002

Dengbin Ma , Jiayi Li , Hui Li , Yao Tang , Xia Gao , Hong Chen , Xiaoyun Qian , Xiaohui Shen

引用次数: 0

Engineering neuroblastoma models for clinical translation 用于临床翻译的神经母细胞瘤工程模型

Q1 Medicine

Engineered regeneration

Pub Date : 2025-01-01 DOI: 10.1016/j.engreg.2025.05.002

Taiyu Song , Rui Liu , Feika Bian , Bin Kong , Jingjing Gan

Neuroblastoma is a profoundly heterogenous extracranial solid tumor in pediatric patients. Elevated risk grade of neuroblastoma has been correlated with unsatisfactory prognosis and resistance to chemotherapy. Despite multimodal therapies exploited for killing neuroblastoma tumor cells, in high-risk neuroblastoma patients, the long-term survival is currently less than 50%. Promising approaches to evaluating the extent of heterogeneity via gene expression profiling of cell subpopulations within individual tumors are still lacking. There is uncertainty about the cross-talk between neuroblastoma cells and other non-neoplastic cell components in the tumor microenvironment. Recently, concerns about individualized eradication therapies have advanced the demand for the diversified construction of neuroblastoma tumor models. This review briefly introduces the genetic variation, subpopulations, and tumor microenvironment aspects of neuroblastoma heterogeneity. Then, we summarize recent methods of constructing tumor models to mimic the biological features of neuroblastoma tumors in vitro. Finally, we conclude the future trends and perspectives in neuroblastoma tumor therapy.

神经母细胞瘤是儿科患者的一种深度异质性颅外实体瘤。神经母细胞瘤的危险等级升高与预后不佳和化疗耐药有关。尽管采用了多种治疗方法来杀死神经母细胞瘤肿瘤细胞，但在高危神经母细胞瘤患者中，长期生存率目前低于50%。通过单个肿瘤细胞亚群的基因表达谱来评估异质性程度的有希望的方法仍然缺乏。神经母细胞瘤细胞与肿瘤微环境中其他非肿瘤细胞组分之间的相互作用尚不确定。近年来，对个体化根除治疗的关注提高了对神经母细胞瘤肿瘤模型多样化构建的需求。本文简要介绍了神经母细胞瘤异质性的遗传变异、亚群和肿瘤微环境。然后，我们总结了近年来在体外模拟神经母细胞瘤肿瘤生物学特征的肿瘤模型构建方法。最后，我们总结了神经母细胞瘤治疗的未来趋势和展望。

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引用次数: 0

Force induces axon growth in inhibitory conditions 力在抑制条件下诱导轴突生长

Q1 Medicine

Engineered regeneration

Pub Date : 2025-01-01 DOI: 10.1016/j.engreg.2025.05.003

Elena Capitanini , Laura Talarico , Sara De Vincentiis , Chiara Giacomelli , Sara Vitolo , Lorenzo Da Palmata , Laura Marchetti , Elisabetta Ferraro , Maria Letizia Trincavelli , Vittoria Raffa

Axon navigation is guided by spatial patterns of chemical and physical cues in the developing central nervous system. Following injury, these patterns are disrupted, the microenvironment evolves rapidly, and inhibitory molecules create a barrier to the regeneration of severed axons. We have recently developed a technology called nano-pulling designed to stimulate axon growth and regeneration by modulating neuronal mechanotransduction. In this paper, we demonstrate that nano-pulling can induce axon growth in hippocampal neurons even in the presence of repulsive cues, such as chondroitin sulfate proteoglycans, semaphorin 3A, microglial activation, and pro-inflammatory cytokines. Nano-pulling can also enhance the elongation of neural processes in neural progenitors transplanted into an organotypic spinal cord injury model that mimics the tissue complexity and inflammation seen in in vivo models. Our data suggest that nano-pulling could be used as a strategy to manipulate axon growth, overcoming certain extrinsic inhibitory factors.

轴突导航是由发育中的中枢神经系统的化学和物理线索的空间模式引导的。损伤后，这些模式被破坏，微环境迅速进化，抑制分子对断裂轴突的再生产生障碍。我们最近开发了一种叫做纳米拉的技术，旨在通过调节神经元的机械转导来刺激轴突的生长和再生。在本文中，我们证明了纳米拉力可以诱导海马神经元轴突生长，即使存在排斥信号，如硫酸软骨素蛋白聚糖、信号蛋白3A、小胶质细胞激活和促炎细胞因子。纳米牵拉还可以增强神经祖细胞移植到器官型脊髓损伤模型中的神经过程的伸长，该模型模仿体内模型中的组织复杂性和炎症。我们的数据表明，纳米拉力可以作为一种策略来操纵轴突的生长，克服某些外在的抑制因素。

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引用次数: 0

ORM1 mediates osteoblast/osteoclast crosstalk in adolescent idiopathic scoliosis via RANKL/OPG ratio alteration ORM1通过改变RANKL/OPG比值介导青少年特发性脊柱侧凸的成骨细胞/破骨细胞串扰

Q1 Medicine

Engineered regeneration

Pub Date : 2025-01-01 DOI: 10.1016/j.engreg.2024.07.002

Kai Chen , Mingyuan Yang , Beier Luo , Xiaolong Li , Xiao Zhai, Xiaoyi Zhou, Yushu Bai, Ziqiang Chen, Kai Chen, Ming Li

Adolescent idiopathic scoliosis (AIS), a complex early-onset three-dimensional spinal deformity, remains etiologically ambiguous despite extensive ongoing investigations. Currently, braces and surgeries are primary treatments of AIS, which come with inherent risks and costs. Therefore, there is an urgent need for biotherapeutic targets for AIS. Using human specimens obtained from the clinic, we discovered that ORM1 was expressed in AIS bone tissues. Also, immune cells were found to interact with osteoclasts through the LTB-LTBR pathway, resulting in elevated ORM1 expression, proliferation promotion and differentiation of monocytes/osteoclasts. Protein analysis showed that in ORM1-positive AIS patient-derived osteoblasts, there was an increased expression of RANKL, decreased expression of OPG, and an increased RANKL/OPG ratio. Furthermore, osteoclasts overexpressing ORM1 promoted their own differentiation while inhibiting osteoblast proliferation and function. ORM1 knockdown osteoclasts co-cultured with osteoblasts, along with the addition of leptin, significantly inhibited osteoclast differentiation while promoting osteoblast proliferation and function-related protein expression. In conclusion, ORM1 acts as a detrimental factor in the pathogenesis of Adolescent Idiopathic Scoliosis (AIS) by promoting osteoclast differentiation and inhibiting both the proliferation and function of osteoblasts. This suggests that ORM1 may represent a valuable therapeutic target for AIS.

青少年特发性脊柱侧凸（AIS）是一种复杂的早发性三维脊柱畸形，尽管正在进行广泛的研究，但其病因仍不明确。目前，牙套和手术是AIS的主要治疗方法，但其存在固有的风险和成本。因此，迫切需要AIS的生物治疗靶点。利用临床获得的人体标本，我们发现ORM1在AIS骨组织中表达。此外，免疫细胞通过LTB-LTBR途径与破骨细胞相互作用，导致ORM1表达升高，单核细胞/破骨细胞增殖促进和分化。蛋白分析显示，在orm1阳性的AIS患者源性成骨细胞中，RANKL表达升高，OPG表达降低，RANKL/OPG比值升高。此外，过表达ORM1的破骨细胞在促进自身分化的同时抑制成骨细胞的增殖和功能。ORM1敲低破骨细胞与成骨细胞共培养，同时加入瘦素，显著抑制破骨细胞分化，促进成骨细胞增殖和功能相关蛋白表达。综上所述，ORM1通过促进破骨细胞分化和抑制成骨细胞的增殖和功能，在青少年特发性脊柱侧凸（AIS）的发病过程中起着有害的作用。这表明ORM1可能是AIS的一个有价值的治疗靶点。

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引用次数: 0

Ultrasonic manipulation in tissue engineering 组织工程中的超声操作

Q1 Medicine

Engineered regeneration

Pub Date : 2025-01-01 DOI: 10.1016/j.engreg.2025.03.001

Zijun Guan, Jianbo Huang, Yang Gao, Hongju Zhou, Liyun Wang, Lang Ma, Li Qiu

Ultrasonic waves exert radiation force on cells and other cell size particles, applied in particle manipulation, growth factor delivery, substance cavitation, and single cell tweezing. Featuring in the safe, contactless, precise, and tunable properties and advantages, ultrasonic waves can be used to control cell's locations aiding in the morphogenesis of complex cell systems, which will be widely used in the future generation tissue engineering. In this review, we summarized current application of ultrasonic waves in the field of cell manipulation and tissue engineering. First, we briefly introduced the physical mechanisms of cell manipulation and described the five kinds of device designs including holographic device, tweezer device, stream standing wave device, surface acoustic wave device, and bulk acoustic wave device. Secondly, we concluded recent works to culture tissue cells in certain spatial patterns using ultrasonic device including bone tissue, cartilage, cardiac muscle, skeletal muscle, endothelial, and neurons. Finally, we systematically highlighted the current challenges and future perspectives. It is believed that this cutting review will substantially stimulate the development and widespread utilization of ultrasonic standing wave in future tissue engineering applications.

超声波对细胞和其他细胞大小的粒子施加辐射力，应用于粒子操纵、生长因子传递、物质空化和单细胞镊子。超声波具有安全、无接触、精确、可调等特点，可用于控制细胞的位置，有助于复杂细胞系统的形态发生，将在下一代组织工程中得到广泛应用。本文就超声技术在细胞操作和组织工程领域的应用现状进行综述。首先，我们简要介绍了细胞操纵的物理机制，并描述了全息装置、镊子装置、流驻波装置、表面声波装置和体声波装置五种装置的设计。其次，总结了近年来利用超声装置培养组织细胞的研究成果，包括骨组织、软骨、心肌、骨骼肌、内皮细胞和神经元。最后，我们系统地强调了当前的挑战和未来的展望。相信这一综述将极大地促进超声驻波在未来组织工程中的发展和广泛应用。

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引用次数: 0

Immunomodulating red blood cell coating for mitigation of foreign body reactions 免疫调节红血球涂层减轻异物反应

Q1 Medicine

Engineered regeneration

Pub Date : 2025-01-01 DOI: 10.1016/j.engreg.2025.09.001

Yi Ye , Jinyun Wu , Tao Sun , Minghong Huang , Jiaping Pan , Danjing Hu , Keying Chen , Dawei Wang , Chenxi Wang , Yangkun Shen , Qi Chen , Baolin Huang

Chronic inflammation of biomedical implants usually leads to fibrosis and device malfunction in the long term. To address these issues, a cell-crosslinked coating of red blood cells (RBCs) was developed to imitate a self-friendly biological membrane and camouflage the implants from immune system. Using the widely applied poly(dimethylsiloxane) (PDMS) as a model substrate, a natural polymer hyaluronic acid (HA) layer was constructed upon PDMS (PDMS-HA), which was further decorated with RBCs (PDMS-HA-RBC). Compared to pristine PDMS, both PDMS-HA and PDMS-HA-RBC notably polarized the original macrophages into an anti-inflammatory phenotype (M2) rather than a pro-inflammatory phenotype (M1). Especially, PDMS-HA-RBC exhibited the highest M2/M1 ratios of macrophages, suggesting efficient modulation effects of inflammation reactions by the RBCs coating. Moreover, in vivo results found that PDMS induced considerable foreign body reactions (FBRs) and extensive fibrosis formation. In contrast, PDMS-HA revealed a significantly thinner fibrotic layer while PDMS-HA-RBC induced the least amount of fibrosis. In addition, PDMS-HA-RBC exhibited the highest fluorescent intensity of CD206 (M2 antigen) and the lowest fluorescent intensity of CD86 (M1 antigen). It was speculated that the RBCs coating-mediated macrophage polarization was mainly attributed to the presence of immune escape antigens (such as CD47 and CD59) upon the cell coating. Altogether, our living RBCs coating demonstrated significant potentials in mitigating FBRs of PDMS, indicating their promising applications in surface engineering of various biomedical implants.

生物医学植入物的慢性炎症通常会导致纤维化和设备长期故障。为了解决这些问题，一种细胞交联的红细胞（rbc）涂层被开发出来，以模仿一种自友好的生物膜，并保护植入物免受免疫系统的攻击。以应用广泛的聚二甲基硅氧烷（PDMS）为模型底物，在PDMS （PDMS-HA）上构建天然聚合物透明质酸（HA）层，并在其表面进行红细胞修饰（PDMS-HA- rbc）。与原始PDMS相比，PDMS- ha和PDMS- ha - rbc均明显使原始巨噬细胞极化为抗炎表型（M2）而不是促炎表型（M1）。特别是PDMS-HA-RBC巨噬细胞M2/M1比值最高，提示红细胞包被对炎症反应有有效的调节作用。此外，体内实验结果发现，PDMS诱导了大量的异物反应（FBRs）和广泛的纤维化形成。相比之下，PDMS-HA显示纤维化层明显变薄，而PDMS-HA- rbc诱导的纤维化量最少。此外，PDMS-HA-RBC对M2抗原CD206的荧光强度最高，对M1抗原CD86的荧光强度最低。推测红细胞包被介导的巨噬细胞极化主要是由于细胞包被上存在免疫逃逸抗原（如CD47和CD59）。总之，我们的活红细胞涂层在减轻PDMS的fbr方面显示出显著的潜力，表明它们在各种生物医学植入物的表面工程中具有广阔的应用前景。

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引用次数: 0

MicroRNAs and mRNAs: A comparative analysis in translation and commercialization MicroRNAs和mrna：翻译和商业化的比较分析

Q1 Medicine

Engineered regeneration

Pub Date : 2025-01-01 DOI: 10.1016/j.engreg.2025.04.001

Jamie Cheng , Wubin Bai , Thomas Caranasos

Success with mRNA vaccines has positioned microRNAs as possibly the nextgeneration therapeutics. While mRNAs have demonstrated rapid translation into effective vaccines, microRNAs possess certain advantages in gene regulation, particularly in targeting multiple genes concurrently. Therefore, they are promising for the treatment of cancer and cardiovascular disorders. This paper provides information about microRNAs with regard to their therapeutic applications, based on their stability, tissue distribution, and specific gene modulation. However, commercialization of microRNA also faces challenges, especially in aspects of delivery and regulatory approval. Unlike the mRNAs, which benefit from the delivery method of lipid nanoparticles, the microRNAs need an innovative delivery method that guarantees target efficacy and ensures minimal off-target effects. Additionally, regulatory pathways for microRNAs have not been fully developed and have to be well-assessed for their safety and effectiveness. We propose that microRNAs and mRNAs may exert complementary therapeutic functions, as mRNAs in vaccines are superior while microRNAs offer new roads to treatments in multifactorial diseases. Since these challenges are being overcome, microRNA-based therapies have the potential to revolutionize treatments for gene regulation and thereby affect the future of RNA therapeutics. This paper outlines the therapeutic potential of microRNAs and the steps involved in translation into clinical application.

mRNA疫苗的成功使microrna有可能成为下一代疗法。虽然mrna已被证明可以快速转化为有效的疫苗，但microrna在基因调控方面具有一定优势，特别是在同时靶向多个基因方面。因此，它们有望用于癌症和心血管疾病的治疗。本文提供了关于microrna的信息，关于他们的治疗应用，基于他们的稳定性，组织分布，和特定的基因调节。然而，microRNA的商业化也面临着挑战，特别是在递送和监管审批方面。与受益于脂质纳米颗粒递送方法的mrna不同，microrna需要一种创新的递送方法，以保证靶向效果并确保最小的脱靶效应。此外，microrna的调控途径尚未完全开发，必须对其安全性和有效性进行充分评估。我们提出microRNAs和mrna可能发挥互补的治疗功能，因为mrna在疫苗中具有优势，而microRNAs为多因子疾病的治疗提供了新的途径。由于这些挑战正在被克服，基于微RNA的治疗有可能彻底改变基因调控的治疗方法，从而影响RNA治疗的未来。本文概述了microrna的治疗潜力和转化为临床应用所涉及的步骤。

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引用次数: 0

Transcript-activated collagen matrix for enhanced bone marrow stem cell differentiation and osteochondral repair 转录活化胶原基质增强骨髓干细胞分化和骨软骨修复

Q1 Medicine

Engineered regeneration

Pub Date : 2025-01-01 DOI: 10.1016/j.engreg.2025.03.002

Gang Zhong , Yixuan Luo , Meng Wang , Zhengran Yu , Xuenong Zou , Gang Wang , Fei Chen , Yin Yu

The regeneration of critical-sized osteochondral defects remains a significant challenge due to the limited self-healing capacity of cartilage. Traditional approaches, such as autologous chondrocyte implantation (ACI) and matrix-induced autologous chondrocyte implantation (MACI), have shown promise but are limited by issues like insufficient cell availability, dedifferentiation of chondrocytes during expansion, and the formation of fibrocartilage rather than functional hyaline cartilage. This study presents a promising approach utilizing transcript-activated matrices (TAMs) with mRNA to enhance the therapeutic potential of bone marrow mesenchymal stem cells (BMSCs) in situ. Chemically modified mRNA (cmRNA) encoding transforming growth factor β3 (TGF-β3) was encapsulated in a collagen hydrogel to provide localized, sustained delivery of chondrogenic signals. In a rat model of critical-sized osteochondral defects, this strategy significantly promoted cartilage regeneration, achieving structural and molecular restoration within six weeks. Histological and biochemical analyses revealed robust chondrogenesis, enhanced extracellular matrix deposition, and superior mechanical properties. Moreover, TAM therapy maintained subchondral bone integrity This work highlights the transformative potential of mRNA-activated matrices as a platform technology that not only addresses key limitations of existing cartilage repair strategies but also provides a biomimetic microenvironment that guides stem cell differentiation and tissue regeneration.

由于软骨的自愈能力有限，骨软骨缺损的再生仍然是一个重大的挑战。传统的方法，如自体软骨细胞植入（ACI）和基质诱导的自体软骨细胞植入（MACI），已经显示出前景，但受到诸如细胞可用性不足、软骨细胞在扩张过程中去分化以及形成纤维软骨而不是功能透明软骨等问题的限制。本研究提出了一种利用mRNA转录激活基质（TAMs）原位增强骨髓间充质干细胞（BMSCs）治疗潜力的有希望的方法。将编码转化生长因子β3 （TGF-β3）的化学修饰mRNA （cmRNA）包裹在胶原水凝胶中，以提供局部、持续的软骨生成信号传递。在大鼠骨软骨缺损模型中，该策略显著促进了软骨再生，在6周内实现了结构和分子的修复。组织学和生化分析显示强健的软骨形成，增强的细胞外基质沉积和优越的力学性能。此外，TAM治疗保持了软骨下骨的完整性。这项工作强调了mrna激活基质作为平台技术的转化潜力，它不仅解决了现有软骨修复策略的关键限制，而且提供了一个引导干细胞分化和组织再生的仿生微环境。

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引用次数: 0

Corrigendum to “Conductive PS inverse opals for regulating proliferation and differentiation of neural stem cells” [Engineered Regeneration 4 (2023) 214-221] “用于调节神经干细胞增殖和分化的导电PS逆蛋白石”的勘误表[工程再生4 (2023)214-221]

Q1 Medicine

Engineered regeneration

Pub Date : 2025-01-01 DOI: 10.1016/j.engreg.2025.12.001

Yangnan Hu , Han Zhang , Hao Wei , Menghui Liao , Xiaoyan Chen , Jiayue Xing , Lian Duan , Cuntu Cheng , Weicheng Lu , Xuechun Yang , Peina Wu , Huan Wang , Jingdun Xie , Renjie Chai

引用次数: 0

Mapping the trajectory of organoid research: Insights into complex models and advanced technologies 绘制类器官研究的轨迹：对复杂模型和先进技术的见解

Q1 Medicine

Engineered regeneration

Pub Date : 2025-01-01 DOI: 10.1016/j.engreg.2025.11.003

Yiming Zhang , Lianyong Wang , Qingqian Zhao , Jinhao Gong , Ye Tian , Yang Liu , Shanfeng Chen , Xin Zhao , Qiang Yang , Yanhong Zhao

In recent years, organoid technology has become a pivotal advancement in stem cell research, offering an unprecedented experimental platform that mimics the morphology and function of human organs, pushing modern life sciences to the forefront. This technology has successfully developed complex three-dimensional (3D) structures derived from human pluripotent or adult stem cells, closely resembling natural organs in tissue and function. Organoid models facilitate in-depth studies of organ development, disease progression, and drug interactions, effectively addressing ethical and practical limitations in traditional biomedical research. Despite its promising development, organoid technology faces challenges in practical applications, particularly in constructing complex organs like the brain, heart, and bone tissue. Therefore, we conducted a bibliometric analysis of 8051 publications on organoids from the Web of Science Core Collection (WoSCC) database (2000-2025). These studies were categorized into five clusters related to current situations and future application directions. Based on our bibliometric analysis, systematically summarize the development of organoid technologies, from laboratory to preclinical applications, exploration of complex organoids, and advanced technologies, while analyzing their limitations and prospects. This review will provide an objective perspective to identify current trends in organoid research and provide new insights into the future research and clinical applications of organoids by teasing out the past-present of organoid research.

近年来，类器官技术已成为干细胞研究的关键进展，提供了一个前所未有的模拟人体器官形态和功能的实验平台，将现代生命科学推向了前沿。这项技术已经成功地从人类多能干细胞或成体干细胞中开发出复杂的三维（3D）结构，在组织和功能上与自然器官非常相似。类器官模型促进了器官发育、疾病进展和药物相互作用的深入研究，有效地解决了传统生物医学研究中的伦理和实践限制。尽管发展前景广阔，但类器官技术在实际应用中仍面临挑战，特别是在构建复杂器官如大脑、心脏和骨组织方面。因此，我们对Web of Science Core Collection （WoSCC）数据库（2000-2025）中8051篇关于类器官的出版物进行了文献计量学分析。根据研究现状和未来应用方向，将这些研究分为五大类。在文献计量学分析的基础上，系统总结了类器官技术的发展，从实验室到临床前应用，复杂类器官的探索和先进技术，同时分析了它们的局限性和前景。本文旨在通过梳理类器官研究的过去和现在，为识别类器官研究的当前趋势提供一个客观的视角，并为未来的研究和临床应用提供新的见解。

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引用次数: 0