Bioengineering & Translational Medicine最新文献_第2页

A novel cytoprotective organ perfusion platform for reconstructing homeostasis of DCD liver while alleviating IRI injury 一种新型细胞保护器官灌注平台，用于重建 DCD 肝脏的稳态，同时减轻 IRI 损伤

IF 7.4 2区医学 Q1 ENGINEERING, BIOMEDICAL

Bioengineering & Translational Medicine

Pub Date : 2024-09-23 DOI: 10.1002/btm2.10724

Tingting Lan, Mingxing Yu, Tao Ming, Hong Wang, Juan Deng, Shuhan Cheng, Zhongyang Shen, Deling Kong

Pump is a vital component for expelling the perfusate in small animal isolated organ normothermic machine perfusion (NMP) systems whose flexible structure and rhythmic contraction play a crucial role in maintaining perfusion system homeostasis. However, the continuous extrusion forming with the rigid stationary shaft of the peristaltic pumps can damage cells, leading to metabolic disorders and eventual dysfunction of transplanted organs. Here, we developed a novel biomimetic blood‐gas system (BBGs) for preventing cell damage. This system mimics the cardiac cycle and features an adjustable inspiratory‐to‐expiratory (IE) ratio to mitigate acidosis caused by continuous oxygen inhalation. In our study, adipose stem cells (ADSCs) were cultured within the circulatory system for 10 min, 2, and 4 h. Compared to the peristaltic pump, the BBGs significantly reduced cell apoptosis and morphological injury while enhancing cell proliferation and adhesion. Additionally, when the supernatant from ADSCs was introduced to LPS‐induced macrophages for 24 h, the BBGs group demonstrated a more pronounced anti‐inflammatory effect, characterized by reduced M1 macrophage expression. Besides, with isolated rat livers from donation after circulatory death (DCD) perfusion with ADSCs for 6 h by the BBGs, we detected fewer apoptotic cells and a reduced inflammatory response, evidenced by down‐regulated TNF‐α expression. The development of BBGs demonstrates the feasibility of recreating physiological liquid–gas circulation in vitro, offering an alternative platform for isolated organ perfusion, especially for applications involving cell therapy.

泵是小动物离体器官常温机器灌注（NMP）系统中排出灌注液的重要部件，其灵活的结构和有节奏的收缩对维持灌注系统的平衡起着至关重要的作用。然而，蠕动泵刚性固定轴形成的连续挤压会损伤细胞，导致代谢紊乱，最终导致移植器官功能障碍。在此，我们开发了一种新型仿生血气系统（BBGs）来防止细胞损伤。该系统模仿心动周期，具有可调节的吸气-呼气（IE）比率，以减轻持续吸入氧气造成的酸中毒。在我们的研究中，脂肪干细胞（ADSCs）在循环系统中分别培养了10分钟、2小时和4小时。与蠕动泵相比，BBGs显著减少了细胞凋亡和形态损伤，同时增强了细胞增殖和粘附。此外，将 ADSCs 的上清液引入 LPS 诱导的巨噬细胞 24 小时后，BBGs 组的抗炎效果更明显，其特征是减少了 M1 巨噬细胞的表达。此外，在循环死亡（DCD）后捐献的大鼠离体肝脏中，用BBGs灌注ADSCs 6小时后，我们发现凋亡细胞减少，炎症反应减弱，TNF-α表达下调就是证明。BBG的开发证明了在体外再造生理液-气循环的可行性，为离体器官灌注提供了一个替代平台，特别是在涉及细胞治疗的应用中。

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引用次数: 0

Macrophages overexpressing interleukin‐10 target and prevent atherosclerosis: Regression of plaque formation and reduction in necrotic core 过量表达白细胞介素-10的巨噬细胞能靶向预防动脉粥样硬化：斑块形成的消退和坏死核心的减少

IF 7.4 2区医学 Q1 ENGINEERING, BIOMEDICAL

Bioengineering & Translational Medicine

Pub Date : 2024-09-17 DOI: 10.1002/btm2.10717

Mingyi Wang, Shanshan Zhou, Yingyun Hu, Wei Tong, Hao Zhou, Mingrui Ma, Xingxuan Cai, Zhengbin Zhang, Luo Zhang, Yundai Chen

Atherosclerosis, a slowly progressing inflammatory disease, is characterized by the presence of monocyte‐derived macrophages. Interventions targeting the inflammatory characteristics of atherosclerosis hold promising potential. Although interleukin (IL)‐10 is widely acknowledged for its anti‐inflammatory effects, systemic administration of IL‐10 has limitations due to its short half‐life and significant systemic side effects. In this study, we aimed to investigate the effectiveness of an approach designed to overexpress IL‐10 in macrophages and subsequently introduce these genetically modified cells into ApoE−/− mice to promote atherosclerosis regression. We engineered RAW264.7 cells to overexpress IL‐10 (referred to as IL‐10M) using lentivirus vectors. The IL‐10M exhibited robust IL‐10 secretion, maintained phagocytic function, improved mitochondrial membrane potentials, reduced superoxide production and showed a tendency toward the M2 phenotype when exposed to inflammatory stimuli. IL‐10M can selectively target plaques in ApoE−/− mice and has the potential to reduce plaque area and necrotic core at both early and late stages of plaque progression. Moreover, there was a significant reduction in MMP9, a biomarker associated with plaque rupture, in IL‐10M‐treated plaques from both the early and late intervention groups. Additionally, the administration of IL‐10M showed no obvious side effects. This study serves as proof that cell therapy based on anti‐inflammatory macrophages might be a promising strategy for the intervention of atherosclerosis.

动脉粥样硬化是一种进展缓慢的炎症性疾病，其特点是存在源自单核细胞的巨噬细胞。针对动脉粥样硬化炎症特征的干预措施具有广阔的前景。虽然白细胞介素（IL）-10的抗炎作用已得到广泛认可，但由于其半衰期短且具有明显的全身副作用，因此全身给药具有局限性。在本研究中，我们的目的是研究在巨噬细胞中过表达 IL-10，并随后将这些转基因细胞导入载脂蛋白E-/-小鼠体内以促进动脉粥样硬化消退的方法的有效性。我们利用慢病毒载体改造了 RAW264.7 细胞，使其过表达 IL-10（简称 IL-10M）。IL-10M表现出强劲的IL-10分泌，维持吞噬功能，改善线粒体膜电位，减少超氧化物的产生，并在受到炎症刺激时表现出M2表型倾向。IL-10M可选择性地靶向载脂蛋白E-/-小鼠的斑块，并有可能在斑块进展的早期和晚期减少斑块面积和坏死核心。此外，在早期和晚期干预组中，经IL-10M处理的斑块中与斑块破裂相关的生物标志物MMP9均有明显减少。此外，服用IL-10M无明显副作用。这项研究证明，基于抗炎巨噬细胞的细胞疗法可能是一种很有前景的动脉粥样硬化干预策略。

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引用次数: 0

Correction to “Self-assembly of PEG–PPS polymers and LL-37 peptide nanomicelles improves the oxidative microenvironment and promotes angiogenesis to facilitate chronic wound healing” 更正 "PEG-PPS 聚合物和 LL-37 肽纳米微孔的自组装可改善氧化微环境并促进血管生成，从而促进慢性伤口愈合"

IF 6.1 2区医学 Q1 ENGINEERING, BIOMEDICAL

Bioengineering & Translational Medicine

Pub Date : 2024-09-09 DOI: 10.1002/btm2.10718

Shi R, Qiao J, Sun Q, Hou B, Li B, Zheng J, Zhang Z, Peng Z, Zhou J, Shen B, Deng J, Zhang X. Self-assembly of PEG–PPS polymers and LL-37 peptide nanomicelles improves the oxidative microenvironment and promotes angiogenesis to facilitate chronic wound healing. Bioeng Transl Med. 2023;9(2):e10619. doi:10.1002/btm2.10619

The authors regret some errors have been found in Figure 5, Figure S12, and Figure S15.

In Figure 5, due to the misuse of wound images of the LL-37@PEG–PPS group on day 9, there was a duplication with the wound images of the PEG–PPS group on day 11.

In Figure S12a, due to misuse of images, there was partial overlap of the 0 h images between the control group and PEG–PPS group.

In Figure S15a, unintentional misuse of the in vivo biodistribution image of FITC-LL-37@PEG–PPS in before injection group, which leads to an overlapped with that on day 4.

Shi R、Qiao J、Sun Q、Hou B、Li B、Zheng J、Zhang Z、Peng Z、Zhou J、Shen B、Deng J、Zhang X. PEG-PPS 聚合物和 LL-37 肽纳米小室的自组装改善了氧化微环境并促进了血管生成，从而促进了慢性伤口愈合。Bioeng Transl Med.2023;9(2):e10619. doi:10.1002/btm2.10619作者对图 5、图 S12 和图 S15 中发现的一些错误表示遗憾。在图 5 中，由于误用了第 9 天 LL-37@PEG-PPS 组的伤口图像，导致与第 11 天 PEG-PPS 组的伤口图像重复。图 S12a 中，由于误用图像，对照组和 PEG-PPS 组的 0 h 图像有部分重叠。图 S15a 中，注射前组的 FITC-LL-37@PEG-PPS 体内生物分布图像被无意误用，导致与第 4 天的图像重叠。

引用次数: 0

Elucidating the role of carrier proteins in cytokine stabilization within double emulsion‐based polymeric nanoparticles 阐明载体蛋白在双乳液基聚合物纳米粒子中稳定细胞因子的作用

IF 7.4 2区医学 Q1 ENGINEERING, BIOMEDICAL

Bioengineering & Translational Medicine

Pub Date : 2024-09-06 DOI: 10.1002/btm2.10722

Emily R. Rhodes, Nicole B. Day, Emma C. Aldrich, C. Wyatt Shields, Kayla G. Sprenger

Polymeric micro‐ and nanoparticles are useful vehicles for delivering cytokines to diseased tissues such as solid tumors. Double emulsion solvent evaporation is one of the most common techniques to formulate cytokines into vehicles made from hydrophobic polymers; however, the liquid–liquid interfaces formed during emulsification can greatly affect the stability and therapeutic performance of encapsulated cytokines. To develop more effective cytokine‐delivery systems, a clear molecular understanding of the interactions between relevant proteins and solvents used in the preparation of such particles is needed. We utilized an integrated computational and experimental approach for studying the governing mechanisms by which interleukin‐12 (IL‐12), a clinically relevant cytokine, is protected from denaturation by albumin, a common stabilizing protein, at an organic‐aqueous solvent interface formed during double emulsification. We investigated protein–protein interactions between human (h)IL‐12 and albumin and simulated these components in pure water, dichloromethane (DCM), and along a water/DCM interface to replicate the solvent regimes formed during double emulsification. We observed that (i) hIL‐12 experiences increased structural deviations near the water/DCM interface, and (ii) hIL‐12 structural deviations are reduced in the presence of albumin. Experimentally, we found that hIL‐12 bioactivity is retained when released from particles in which albumin is added to the aqueous phase in molar excess to hIL‐12 and sufficient time is allowed for albumin‐hIL‐12 binding. Findings from this work have implications in establishing design principles to enhance the stability of cytokines and other unstable proteins in particles formed by double emulsification for improved stability and therapeutic efficacy.

聚合物微粒和纳米粒子是向实体瘤等病变组织输送细胞因子的有效载体。双乳液溶剂蒸发是将细胞因子配制成疏水聚合物载体的最常用技术之一；然而，乳化过程中形成的液-液界面会极大地影响封装细胞因子的稳定性和治疗效果。为了开发更有效的细胞因子递送系统，我们需要从分子角度清楚地了解相关蛋白质与用于制备此类微粒的溶剂之间的相互作用。我们采用了一种计算与实验相结合的方法来研究白细胞介素-12（IL-12）（一种临床相关细胞因子）在双乳化过程中形成的有机-水溶剂界面上受到白蛋白（一种常见的稳定蛋白）保护而不变性的调节机制。我们研究了人（h）IL-12 和白蛋白之间的蛋白-蛋白相互作用，并模拟了这些成分在纯水、二氯甲烷（DCM）和水/二氯甲烷界面中的情况，以复制双乳化过程中形成的溶剂体系。我们观察到：(i) hIL-12 在水/DCM 界面附近的结构偏差增大；(ii) hIL-12 的结构偏差在有白蛋白存在时减小。在实验中，我们发现当白蛋白以超过 hIL-12 的摩尔量添加到水相颗粒中，并有足够的时间让白蛋白与 hIL-12 结合时，hIL-12 的生物活性就会被释放出来。这项工作的发现有助于确立设计原则，提高细胞因子和其他不稳定蛋白质在双乳化形成的微粒中的稳定性，从而提高稳定性和疗效。

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引用次数: 0

A stretchable human lung‐on‐chip model of alveolar inflammation for evaluating anti‐inflammatory drug response 用于评估抗炎药物反应的肺泡炎症可拉伸人肺芯片模型

IF 7.4 2区医学 Q1 ENGINEERING, BIOMEDICAL

Bioengineering & Translational Medicine

Pub Date : 2024-09-05 DOI: 10.1002/btm2.10715

Clémentine Richter, Lorenz Latta, Daria Harig, Patrick Carius, Janick D. Stucki, Nina Hobi, Andreas Hugi, Paul Schumacher, Tobias Krebs, Alexander Gamrekeli, Felix Stöckle, Klaus Urbschat, Galia Montalvo, Franziska Lautenschläger, Brigitta Loretz, Alberto Hidalgo, Nicole Schneider‐Daum, Claus‐Michael Lehr

This study describes a complex human in vitro model for evaluating anti‐inflammatory drug response in the alveoli that may contribute to the reduction of animal testing in the pre‐clinical stage of drug development. The model is based on the human alveolar epithelial cell line Arlo co‐cultured with macrophages differentiated from the THP‐1 cell line, creating a physiological biological microenvironment. To mimic the three‐dimensional architecture and dynamic expansion and relaxation of the air‐blood‐barrier, they are grown on a stretchable microphysiological lung‐on‐chip. For validating the in vitro model, three different protocols have been developed to demonstrate the clinically established anti‐inflammatory effect of glucocorticoids to reduce certain inflammatory markers after different pro‐inflammatory stimuli: (1) an inflammation caused by bacterial LPS (lipopolysaccharides) to simulate an LPS‐induced acute lung injury measured best with cytokine IL‐6 release; (2) an inflammation caused by LPS at ALI (air‐liquid interface) to investigate aerosolized anti‐inflammatory treatment, measured with chemokine IL‐8 release; and (3) an inflammation with a combination of human inflammatory cytokines TNFα and IFNγ to simulate a critical cytokine storm leading to epithelial barrier disruption, where the eventual weakening or protection of the epithelial barrier can be measured. In all cases, the presence of macrophages appeared to be crucial to mediating inflammatory changes in the alveolar epithelium. LPS induction led to inflammatory changes independently of stretch conditions. Dynamic stretch, emulating breathing‐like mechanics, was essential for in vitro modeling of the clinically relevant outcome of epithelial barrier disruption upon TNFα/IFNγ‐induced inflammation.

本研究描述了一种复杂的人体体外模型，用于评估抗炎药物在肺泡中的反应，该模型可能有助于减少药物开发临床前阶段的动物试验。该模型基于人肺泡上皮细胞系 Arlo 与 THP-1 细胞系分化出的巨噬细胞共同培养，创造了一个生理生物微环境。为了模拟气血屏障的三维结构和动态扩张与松弛，它们生长在可拉伸的微生理肺芯片上。为了验证体外模型，我们制定了三种不同的方案，以证明糖皮质激素在不同促炎刺激后减少某些炎症指标的临床公认抗炎效果：(1)细菌LPS（脂多糖）引起的炎症，模拟LPS诱导的急性肺损伤，最好用细胞因子IL-6释放来测量；(2)LPS在ALI（空气-液体界面）引起的炎症，研究气溶胶抗炎治疗，用趋化因子IL-8释放来测量；(3) 结合使用人类炎症细胞因子 TNFα 和 IFNγ 引起的炎症，以模拟导致上皮屏障破坏的临界细胞因子风暴，从而测量上皮屏障的最终削弱或保护情况。在所有情况下，巨噬细胞的存在似乎对肺泡上皮的炎症变化至关重要。LPS 诱导的炎症变化与拉伸条件无关。仿呼吸力学的动态拉伸对于体外模拟 TNFα/IFNγ 诱导炎症时上皮屏障破坏的临床相关结果至关重要。

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引用次数: 0

Correction to “Doxorubicin-loaded nanoparticle coated with endothelial cells-derived exosomes for immunogenic chemotherapy of glioblastoma” 对 "涂有内皮细胞衍生外泌体的多柔比星负载纳米粒子用于胶质母细胞瘤的免疫原性化疗 "的更正

IF 6.1 2区医学 Q1 ENGINEERING, BIOMEDICAL

Bioengineering & Translational Medicine

Pub Date : 2024-09-05 DOI: 10.1002/btm2.10719

Zhang C, Song J, Lou L, et al. Doxorubicin-loaded nanoparticle coated with endothelial cells-derived exosomes for immunogenic chemotherapy of glioblastoma. Bioeng Transl Med 2020;6(3):e10203.

We apologize for this error.

Zhang C, Song J, Lou L, et al. 内皮细胞衍生的外泌体包被的多柔比星纳米颗粒用于胶质母细胞瘤的免疫原性化疗。Bioeng Transl Med 2020;6(3):e10203.We apologize for this error.

引用次数: 0

Advances in bioengineered CAR T/NK cell therapy for glioblastoma: Overcoming immunosuppression and nanotechnology‐based strategies for enhanced CAR T/NK cell therapy 胶质母细胞瘤生物工程 CAR T/NK 细胞疗法的进展：克服免疫抑制和基于纳米技术的增强 CAR T/NK 细胞疗法策略

IF 7.4 2区医学 Q1 ENGINEERING, BIOMEDICAL

Bioengineering & Translational Medicine

Pub Date : 2024-08-31 DOI: 10.1002/btm2.10716

Nasim Dana, Arezou Dabiri, Majed Bahri Najafi, Azadeh Rahimi, Sayed Mohammad Matin Ishaghi, Laleh Shariati, Minmin Shao, Assunta Borzacchiello, Ilnaz Rahimmanesh, Pooyan Makvandi

Glioblastoma is a strong challenge in the worldwide field of central nervous system malignancies. GBM's inherent heterogeneity, along with the formation of an immunosuppressive tumor microenvironment, supports its resistance to current therapy methods. Immunotherapeutic methods have emerged as potential options in recent years. However, because of the inherent limits of traditional immunotherapeutic techniques innovative approaches are required. Advances in cut‐edge techniques provide a possible route for improving effector cell effectiveness. This review gives insight into the complicated immunosuppressive pathways in GBM, with a particular emphasis on CAR T/NK‐cell treatment as a potential achievement. Recognizing and addressing these concerns might open the way for more effective and focused glioblastoma therapies, providing hope for the future with the aim of improved outcomes for patients. In addition, this review presents valuable insights into the integration of nanotechnology into CAR T/NK cell therapy for enhanced efficiency of these personalized gene therapy products.

胶质母细胞瘤是世界范围内中枢神经系统恶性肿瘤领域的一个严峻挑战。胶质母细胞瘤固有的异质性以及免疫抑制性肿瘤微环境的形成，使其对目前的治疗方法产生了抗药性。近年来，免疫治疗方法已成为潜在的选择。然而，由于传统的免疫治疗技术存在固有的局限性，因此需要创新的方法。尖端技术的进步为提高效应细胞的有效性提供了可能的途径。本综述深入探讨了 GBM 复杂的免疫抑制途径，并特别强调了 CAR T/NK 细胞治疗这一潜在成果。认识并解决这些问题可能会为更有效、更有针对性的胶质母细胞瘤疗法开辟道路，为未来带来希望，从而改善患者的预后。此外，本综述还就如何将纳米技术融入 CAR T/NK 细胞疗法以提高这些个性化基因治疗产品的效率提出了宝贵的见解。

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引用次数: 0

In situ-crosslinked Zippersomes enhance cardiac repair by increasing accumulation and retention 原位交联的 Zippersomes 可通过增加积累和保留来促进心脏修复。

IF 6.1 2区医学 Q1 ENGINEERING, BIOMEDICAL

Bioengineering & Translational Medicine

Pub Date : 2024-08-20 DOI: 10.1002/btm2.10697

Natalie E. Jasiewicz, Kuo-Ching Mei, Hannah M. Oh, Emily E. Bonacquisti, Ameya Chaudhari, Camryn Byrum, Brian C. Jensen, Juliane Nguyen

Mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) are a promising treatment for myocardial infarction (MI), but their therapeutic efficacy is limited by inefficient accumulation at the target site. A minimally invasive MSC EV therapy that enhances EV accumulation at the disease site and extends EV retention could significantly improve post-infarct cardiac regeneration. Here, we show that EVs decorated with the next-generation of high-affinity (HiA) heterodimerizing leucine zippers, termed HiA Zippersomes, amplify targetable surface areas through in situ crosslinking and exhibited ~7-fold enhanced accumulation within the infarcted myocardium in mice after 3 days and continued to be retained up to Day 21, surpassing the performance of unmodified EVs. After MI in mice, HiA Zippersomes increase the ejection fraction by 53% and 100% compared with unmodified EVs and phosphate-buffered saline (PBS), respectively. This notable improvement in cardiac function played a crucial role in restoring healthy heart performance. HiA Zippersomes also robustly decrease infarct size by 52% and 60% compared with unmodified EVs and PBS, respectively, thus representing a promising platform for minimally invasive vesicle delivery to the infarcted heart compared to intramyocardial injections.

间充质干细胞（MSC）衍生的细胞外囊泡（EVs）是治疗心肌梗死（MI）的一种有前景的方法，但其疗效因在目标部位的低效积累而受到限制。微创间充质干细胞EV疗法能增强EV在疾病部位的积累并延长EV的保留时间，从而显著改善梗死后的心脏再生。在这里，我们展示了用新一代高亲和力（HiA）异二聚体亮氨酸拉链（称为 HiA Zippersomes）装饰的 EVs，它们通过原位交联扩大了可靶向的表面区域，3 天后在小鼠梗死心肌内的蓄积增强了约 7 倍，并持续保留到第 21 天，超过了未修饰 EVs 的表现。小鼠发生心肌梗死后，与未修饰的 EVs 和磷酸盐缓冲盐水（PBS）相比，HiA Zippersomes 可使射血分数分别提高 53% 和 100%。心脏功能的显著改善在恢复健康心脏性能方面发挥了关键作用。与未修饰的EVs和磷酸盐缓冲盐水（PBS）相比，HiA Zippersomes还能使梗死面积分别缩小52%和60%，因此与心肌内注射相比，HiA Zippersomes是向梗死心脏提供微创囊泡的理想平台。

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引用次数: 0

Targeting the epigenome with advanced delivery strategies for epigenetic modulators 以表观基因组为目标，采用先进的表观遗传调节剂递送策略

IF 7.4 2区医学 Q1 ENGINEERING, BIOMEDICAL

Bioengineering & Translational Medicine

Pub Date : 2024-08-17 DOI: 10.1002/btm2.10710

Sonia Guha, Yogeswaran Jagadeesan, Murali Monohar Pandey, Anupama Mittal, Deepak Chitkara

Epigenetics mechanisms play a significant role in human diseases by altering DNA methylation status, chromatin structure, and/or modifying histone proteins. By modulating the epigenetic status, the expression of genes can be regulated without any change in the DNA sequence itself. Epigenetic drugs exhibit promising therapeutic efficacy against several epigenetically originated diseases including several cancers, neurodegenerative diseases, metabolic disorders, cardiovascular disorders, and so forth. Currently, a considerable amount of research is focused on discovering new drug molecules to combat the existing research gap in epigenetic drug therapy. A novel and efficient delivery system can be established as a promising approach to overcome the drawbacks associated with the current epigenetic modulators. Therefore, formulating the existing epigenetic drugs with distinct encapsulation strategies in nanocarriers, including solid lipid nanoparticles, nanogels, bio‐engineered nanocarriers, liposomes, surface modified nanoparticles, and polymer–drug conjugates have been examined for therapeutic efficacy. Nonetheless, several epigenetic modulators are untouched for their therapeutic potential through different delivery strategies. This review provides a comprehensive up to date discussion on the research findings of various epigenetics mechanism, epigenetic modulators, and delivery strategies utilized to improve their therapeutic outcome. Furthermore, this review also highlights the recently emerged CRISPR tool for epigenome editing.

表观遗传学机制通过改变 DNA 甲基化状态、染色质结构和/或修饰组蛋白，在人类疾病中发挥着重要作用。通过调节表观遗传状态，可以在不改变 DNA 序列本身的情况下调节基因的表达。表观遗传药物对几种由表观遗传引起的疾病，包括几种癌症、神经退行性疾病、代谢紊乱、心血管疾病等具有良好的疗效。目前，大量研究都集中在发现新的药物分子上，以填补表观遗传药物治疗领域现有的研究空白。建立新颖高效的给药系统是克服现有表观遗传调节剂弊端的有效方法。因此，研究人员采用不同的封装策略将现有的表观遗传药物配制成纳米载体，包括固体脂质纳米颗粒、纳米凝胶、生物工程纳米载体、脂质体、表面修饰纳米颗粒和聚合物-药物共轭物，以研究其疗效。然而，还有一些表观遗传调节剂尚未通过不同的递送策略发挥其治疗潜力。本综述对各种表观遗传学机制、表观遗传学调节剂以及用于改善治疗效果的给药策略的研究成果进行了全面的最新讨论。此外，本综述还重点介绍了最近出现的用于表观基因组编辑的 CRISPR 工具。

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引用次数: 0

A temperature responsive hydrogel encapsulated with adipose‐derived stem cells and melanin promotes repair and regeneration of endometrial injury 包裹了脂肪干细胞和黑色素的温度响应水凝胶可促进子宫内膜损伤的修复和再生

IF 7.4 2区医学 Q1 ENGINEERING, BIOMEDICAL

Bioengineering & Translational Medicine

Pub Date : 2024-08-16 DOI: 10.1002/btm2.10714

Ruigao Song, Chicheng Ma, Hongxia Li, Yu Cheng, Xianmei Cui, Zanhong Wang, Lijuan Huang, Chunying Song, Yukai Jing, Bing Cao, Lili Wang, Qing Tian, Xi Wang, Ruiping Zhang, Hanwang Zhang

The endometrium, the inner lining of the uterus, assumes a crucial role in the female reproductive system. Disorders and injuries impacting the endometrium can lead to profound consequences, including infertility and compromised women's overall health. Recent advancements in stem cell research have opened new possibilities for the treatment and repair of endometrial issues. In the present study, we constructed a degradable hydrogel by loading adipose‐derived stem cells (ADSCs) and melanin nanoparticles (MNP). In vitro cell experiments validated the biocompatibility of the prepared hydrogels and their adeptness in encapsulating ADSCs. Subsequently, we explored the impact of hydrogel@ADSC@MNP constructs in the healing process of uterine injury in mice. The results indicated that hydrogel@ADSC@MNP could augment endometrial thickness and ameliorate endometrial interstitial fibrosis. The injured tissue adjacent to hydrogel@ADSC@MNP constructs exhibited higher levels of bFGF, IGF‐1, and VEGFA compared with the corresponding tissue in mice receiving hydrogel constructs alone or in the model group. Furthermore, the hydrogel@ADSC@MNP system enhanced the proliferative capabilities of uterine endometrial cells, facilitated microvasculature regeneration, and reinstated the endometrium's capacity to receive the embryos. Our findings strongly suggest that the hydrogel@ADSC@MNP system holds significant promise for repairing and regenerating damaged endometrium.

子宫内膜是子宫的内壁，在女性生殖系统中起着至关重要的作用。影响子宫内膜的疾病和损伤可导致严重后果，包括不孕不育和损害妇女的整体健康。干细胞研究的最新进展为治疗和修复子宫内膜问题提供了新的可能性。在本研究中，我们通过负载脂肪来源干细胞（ADSCs）和黑色素纳米颗粒（MNP）构建了一种可降解水凝胶。体外细胞实验验证了所制备水凝胶的生物相容性及其包裹 ADSCs 的能力。随后，我们探讨了水凝胶@ADSC@MNP构建物对小鼠子宫损伤愈合过程的影响。结果表明，水凝胶@ADSC@MNP能增加子宫内膜厚度，改善子宫内膜间质纤维化。与单独接受水凝胶构建物的小鼠或模型组的相应组织相比，水凝胶@ADSC@MNP构建物附近的损伤组织显示出更高水平的bFGF、IGF-1和VEGFA。此外，水凝胶@ADSC@MNP 系统增强了子宫内膜细胞的增殖能力，促进了微血管再生，并恢复了子宫内膜接收胚胎的能力。我们的研究结果有力地表明，水凝胶@ADSC@MNP系统在修复和再生受损子宫内膜方面大有可为。

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引用次数: 0