Bioengineering & Translational Medicine最新文献_第4页

Fiber‐Electrospun Hydrogel Therapy for DNP: A synergistic electrospun‐hydrogel composite for alleviating diabetic neuropathic pain via MMP9 regulation and sodium channel inhibition 纤维-电纺丝水凝胶治疗DNP：一种通过MMP9调节和钠通道抑制来减轻糖尿病神经性疼痛的协同电纺丝-水凝胶复合材料

IF 7.4 2区医学

Bioengineering & Translational Medicine Pub Date : 2025-07-29 DOI: 10.1002/btm2.70050

Wen Chen, Ji Chen, Yingqing Lu, Yangyuxi Chen, Xinxin Liu, Fengrui Yang

{"title":"Fiber‐Electrospun Hydrogel Therapy for DNP: A synergistic electrospun‐hydrogel composite for alleviating diabetic neuropathic pain via MMP9 regulation and sodium channel inhibition","authors":"Wen Chen, Ji Chen, Yingqing Lu, Yangyuxi Chen, Xinxin Liu, Fengrui Yang","doi":"10.1002/btm2.70050","DOIUrl":"https://doi.org/10.1002/btm2.70050","url":null,"abstract":"Diabetic neuropathic pain (DNP) remains a significant challenge in diabetes care, and effective therapeutic strategies are urgently needed. This study introduces an innovative electrospinning‐hydrogel composite, Fiber‐SIN/Gel‐LidC, designed for the controlled and synergistic release of Sinomenine (SIN) and Lidocaine (Lid). Bioinformatics and network pharmacology analyses identified MMP9 as a key player in DNP alleviation. The composite, composed of SIN‐loaded fibers and Lid microcrystals, ensures sustained drug release over 7 days, demonstrating excellent biocompatibility. In vivo experiments on diabetic rats revealed significant improvements in thermal and mechanical pain thresholds, along with a reduction in sciatic nerve excitability. Additionally, the composite significantly attenuated neuroinflammation, neuronal apoptosis, and morphological damage. Mechanistic studies highlighted the neuroprotective effects of Fiber‐SIN/Gel‐LidC, particularly through the regulation of MMP9 and inhibition of sodium channels. These findings suggest that Fiber‐SIN/Gel‐LidC holds great potential as an innovative biomaterial‐based approach for managing DNP, offering promising therapeutic prospects for diabetic neuropathy.","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"68 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144747472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Neuron‐targeted 2‐deoxyglucose‐dendrimer‐rosiglitazone nanotherapy mitigates neuroinflammation and cognitive deficits in pediatric traumatic brain injury 神经元靶向2 -脱氧葡萄糖-树突状聚合物-罗格列酮纳米疗法减轻小儿创伤性脑损伤的神经炎症和认知缺陷

IF 7.4 2区医学

Bioengineering & Translational Medicine Pub Date : 2025-07-23 DOI: 10.1002/btm2.70053

Aqib Iqbal Dar, Zhi Zhang, Shamila Gopalakrishnan, Rishi Sharma, Anunay James Pulukuri, Anu Rani, Anubhav Dhull, Joan Castaneda Gonzalez, Tia Atoui, Yara Mashal, Zahrah Naseer, Julia Calmi, Anjali Sharma

{"title":"Neuron‐targeted 2‐deoxyglucose‐dendrimer‐rosiglitazone nanotherapy mitigates neuroinflammation and cognitive deficits in pediatric traumatic brain injury","authors":"Aqib Iqbal Dar, Zhi Zhang, Shamila Gopalakrishnan, Rishi Sharma, Anunay James Pulukuri, Anu Rani, Anubhav Dhull, Joan Castaneda Gonzalez, Tia Atoui, Yara Mashal, Zahrah Naseer, Julia Calmi, Anjali Sharma","doi":"10.1002/btm2.70053","DOIUrl":"https://doi.org/10.1002/btm2.70053","url":null,"abstract":"Traumatic brain injury (TBI) remains a major global health challenge, characterized by high morbidity and mortality rates. Despite advances in neuroscience, the blood–brain barrier (BBB) limits the effectiveness of potential neuroprotective treatments. Recent nanotechnology breakthroughs have led to smart drug delivery systems that can cross the BBB and target injured brain areas. However, achieving the specificity needed to deliver therapies to affected neurons remains a challenge. In previous work, we developed a mixed‐layered dendrimer functionalized with 2‐deoxyglucose (2DG‐D) for selective neuronal drug delivery. In this study, we explore the therapeutic potential of rosiglitazone (Rosi) for pediatric TBI by creating a 2DG‐D‐Rosi nanosystem, where Rosi is conjugated to 2DG‐D to improve its solubility, bioavailability, and targeted delivery to injured neurons. In vitro, 2DG‐D‐Rosi demonstrated high neuronal uptake, sustained drug release, and excellent biocompatibility. It significantly reduced neuronal apoptosis, reactive oxygen species formation, pro‐inflammatory cytokine expression, and caspase activity, outperforming free Rosi. In vivo, using a pediatric TBI mouse model, 2DG‐D‐Rosi improved neuronal targeting, reduced neuroinflammation, and enhanced behavioral outcomes. This research highlights 2DG‐D‐Rosi as a promising nanotherapeutic platform for precise TBI treatment and sets the stage for developing more effective therapies for this challenging condition.","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"1 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144684430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Engineering biomimetic nanovesicles for PEBP1 mRNA delivery to inhibit ferroptosis in abdominal aortic aneurysm 工程仿生纳米囊递送PEBP1 mRNA抑制腹主动脉瘤铁下垂

IF 5.7 2区医学

Bioengineering & Translational Medicine Pub Date : 2025-07-21 DOI: 10.1002/btm2.70025

Lulu Chen, Bicheng Chen, Xiang Su

{"title":"Engineering biomimetic nanovesicles for PEBP1 mRNA delivery to inhibit ferroptosis in abdominal aortic aneurysm","authors":"Lulu Chen, Bicheng Chen, Xiang Su","doi":"10.1002/btm2.70025","DOIUrl":"10.1002/btm2.70025","url":null,"abstract":"An abdominal aortic aneurysm (AAA) is a life-threatening vascular condition characterized by the dilation of the abdominal aorta, with ferroptosis playing a significant role in its pathogenesis. This study investigates the therapeutic potential of engineering biomimetic nanovesicles to deliver phosphatidylethanolamine-binding protein 1 (PEBP1) mRNA for inhibiting ferroptosis in vascular smooth muscle cells (VSMCs) and preventing AAA progression. Differential gene expression analysis of the AAA transcriptomic dataset GSE57691 identified 243 differentially expressed genes (DEGs), intersecting with 12 ferroptosis-related genes. Single-cell analysis of dataset GSE237230 highlighted PEBP1 as a key gene in VSMCs. Overexpression of PEBP1 in VSMCs enhanced proliferation, reduced reactive oxygen species (ROS) and iron levels, and inhibited apoptosis and ferroptosis via the NRF2/GPX4 axis. The engineered biomimetic nanovesicles demonstrated significant uptake by VSMCs and effective delivery of PEBP1 mRNA. In vivo studies confirmed that these nanovesicles substantially inhibited AAA progression in mice. This study presents a novel bioengineering approach for AAA treatment by targeting ferroptosis through PEBP1 mRNA delivery, offering a promising molecular strategy for the prevention and management of AAA.","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"10 5","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://aiche.onlinelibrary.wiley.com/doi/epdf/10.1002/btm2.70025","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144669697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Dynamic and living devices for overcoming fibrosis of implanted biomaterials 用于克服植入生物材料纤维化的动态和活体装置

IF 7.4 2区医学

Bioengineering & Translational Medicine Pub Date : 2025-07-21 DOI: 10.1002/btm2.70048

Joy M. Jackson, Lolita Testu, Alex Abramson

引用次数: 0

A silicon membrane microfluidic oxygenator for use as an artificial placenta with minimal anticoagulation 一种硅膜微流控充氧器，用于具有最小抗凝作用的人工胎盘

IF 5.7 2区医学

Bioengineering & Translational Medicine Pub Date : 2025-07-12 DOI: 10.1002/btm2.70037

David G. Blauvelt, Nicholas C. Higgins, Anne Hesek, Bianca N. De, Nathan Wright, Prasad Nithianandam, Charles Blaha, Jarrett Moyer, Benjamin W. Chui, Francisco J. Baltazar, Shuvo Roy

{"title":"A silicon membrane microfluidic oxygenator for use as an artificial placenta with minimal anticoagulation","authors":"David G. Blauvelt, Nicholas C. Higgins, Anne Hesek, Bianca N. De, Nathan Wright, Prasad Nithianandam, Charles Blaha, Jarrett Moyer, Benjamin W. Chui, Francisco J. Baltazar, Shuvo Roy","doi":"10.1002/btm2.70037","DOIUrl":"10.1002/btm2.70037","url":null,"abstract":"Extreme prematurity carries a high burden of morbidity and mortality. The artificial placenta is an emerging therapy that has the potential to improve outcomes in these patients. However, current devices in development are limited by inadequate hemocompatibility, a major barrier to the translation of the artificial placenta into humans. Here, we present a novel microfluidic oxygenator that is comprised of a stacked array of semiconductor silicon membranes and operates with minimal anticoagulation (activated clotting time = 120–180 s). We describe the design, construction, and testing of two generations of prototypes. Our Generation 2 Device had an oxygen transfer of 1.51 ± 0.25 volume % (mean ± standard error). Computational fluid dynamics (CFD) modeling demonstrated favorable blood flow properties, including laminar flow, no stasis or recirculation, and optimal wall shear stress. In vivo testing in a 6 hour neonatal swine model showed that the silicon membrane oxygenator could operate with low-dose anticoagulation with minimal clot formation. Furthermore, the oxygenator had no significant effect on markers of animal health, including inflammation (white blood cell count), coagulation (platelet count, prothrombin time), or hemolysis (hematocrit, plasma free hemoglobin). This study represents a key advance toward developing an anticoagulation-free oxygenator and ultimately bringing artificial placenta technology to patients.","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"10 5","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://aiche.onlinelibrary.wiley.com/doi/epdf/10.1002/btm2.70037","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144611070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Revolutionizing nephrocalcinosis treatment: IL‐10 engineered macrophages as a novel therapeutic approach 革命性的肾钙化症治疗：IL - 10工程巨噬细胞作为一种新的治疗方法

IF 7.4 2区医学

Bioengineering & Translational Medicine Pub Date : 2025-07-11 DOI: 10.1002/btm2.70047

Wenlei Zhao, Kailong Wang, Hairui Chen, Junnan Xu, Lequan Wen, Yan Wu, Weihao Chen, Haitao Liu, Yanzhong Liu, Jiqing Zhang, John C. Lieske, Luo Zhang, Xu Zhang, Haixing Mai

{"title":"Revolutionizing nephrocalcinosis treatment: IL‐10 engineered macrophages as a novel therapeutic approach","authors":"Wenlei Zhao, Kailong Wang, Hairui Chen, Junnan Xu, Lequan Wen, Yan Wu, Weihao Chen, Haitao Liu, Yanzhong Liu, Jiqing Zhang, John C. Lieske, Luo Zhang, Xu Zhang, Haixing Mai","doi":"10.1002/btm2.70047","DOIUrl":"https://doi.org/10.1002/btm2.70047","url":null,"abstract":"Nephrocalcinosis provides a nidus for stone formation and is strongly linked to renal injury and chronic kidney disease. Although the crucial role of macrophages in the formation and progression of calcium oxalate (CaOx) crystals has long been widely recognized, finding effective immunotherapies for nephrocalcinosis remains a challenge. In this study, we described an innovative macrophage‐based method that delivers interleukin‐10 (IL‐10) into the kidney, reduces the deposition of CaOx crystals, and alleviates renal injury in a mouse model of glyoxylate‐induced CaOx. Compared with recombinant IL‐10 direct injection, the macrophage‐based method has the advantages of biocompatibility and sustaining action. We found that the transplantation of engineered macrophages via the tail vein significantly reduced the volume of crystals in the kidney, thereby alleviating the kidney injury caused by crystal. In mechanistic studies, IL‐10‐secreting macrophages inhibited crystal formation and promoted crystal clearance by promoting macrophage M2 polarization, exerting a protective effect on renal tissue. Our data suggest that macrophage‐based delivery of IL‐10 to the kidney can be a potential treatment method for nephrocalcinosis.","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"329 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144603231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

USENSE: A proof-of-concept self-screening tool for home-based recurrent urinary tract infection management USENSE：用于家庭复发性尿路感染管理的概念验证自我筛查工具

IF 5.7 2区医学

Bioengineering & Translational Medicine Pub Date : 2025-07-10 DOI: 10.1002/btm2.70038

Antra Ganguly, Ujjaini Basu, Varun Gunda, Ashwin Krishnan, Pranav Ramesh, Kush Jivnani, Arjun Raghuram, Shashank Bhagavatula, Sifa Khan, Philippe Zimmern, Nicole De Nisco, Shalini Prasad

{"title":"USENSE: A proof-of-concept self-screening tool for home-based recurrent urinary tract infection management","authors":"Antra Ganguly, Ujjaini Basu, Varun Gunda, Ashwin Krishnan, Pranav Ramesh, Kush Jivnani, Arjun Raghuram, Shashank Bhagavatula, Sifa Khan, Philippe Zimmern, Nicole De Nisco, Shalini Prasad","doi":"10.1002/btm2.70038","DOIUrl":"10.1002/btm2.70038","url":null,"abstract":"In this work, we report a novel proof-of-concept biosensing diagnostic tool for the multiplexed electrochemical quantitation of a unique combination of three UTI-relevant biomarkers, Prostaglandin E2 (PGE2), Interleukin-8 (IL-8), and Lipopolysaccharide (LPS), in unfiltered human urine. The proposed device, called USENSE, integrates lateral flow microfluidic channels, a gold-based sensor array for quantifying PGE2, IL-8, and LPS levels, and a random forest machine learning model for reliable diagnosis of UTI. The device is unique as it not only acts as a diagnostic device but also provides information on UTI by providing a risk score for UTI recurrence. USENSE is culture-free and label-free, requires no sample preparation at the user end, and can be adapted for use in home-based self-screening. In less than 5 minutes, USENSE directly measures the urinary concentration of PGE2, IL-8, and LPS and provides a UTI severity state classification: 0 = Healthy, 1 = Asymptomatic Bacteriuria, 2 = Symptomatic; low risk of relapse, 3 = Symptomatic; high risk of UTI relapse. In postmenopausal women, the PGE2, IL8, and LPS concentrations measured via the device correlated well with the levels measured using traditional enzyme-linked immunosorbent assay (ELISA). Our machine learning diagnostic model allowed for UTI diagnosis with 93% test accuracy and UTI prognosis state classification with >84% accuracy for the human urine samples tested. Further development of USENSE for clinical and home-based use could create a paradigm shift in point-of-care UTI diagnostics by allowing timely intervention and minimizing unwarranted empirical administration of antibiotics.","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"10 5","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://aiche.onlinelibrary.wiley.com/doi/epdf/10.1002/btm2.70038","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144603274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Patient‐specific visco‐hyperelastic mechanical model for breast tumor localization in surgical planning 手术计划中乳腺肿瘤定位的患者特异性粘弹性力学模型

IF 7.4 2区医学

Bioengineering & Translational Medicine Pub Date : 2025-07-09 DOI: 10.1002/btm2.70044

Felicia Alfano, Pedro Navas, Pablo Lamata, Karla Ferreres García, Juan E. Ortuño, Oscar Bueno Zamora, Santiago Lizarraga, Andrés Santos, Javier Pascau, José M. Goicolea, María J. Ledesma‐Carbayo

{"title":"Patient‐specific visco‐hyperelastic mechanical model for breast tumor localization in surgical planning","authors":"Felicia Alfano, Pedro Navas, Pablo Lamata, Karla Ferreres García, Juan E. Ortuño, Oscar Bueno Zamora, Santiago Lizarraga, Andrés Santos, Javier Pascau, José M. Goicolea, María J. Ledesma‐Carbayo","doi":"10.1002/btm2.70044","DOIUrl":"https://doi.org/10.1002/btm2.70044","url":null,"abstract":"Breast‐conserving surgery is typically performed with the patient in a supine position, whereas preoperative diagnostic MRI breast images are obtained with the patient in a prone position. The change in patient positioning causes significant large deformations, requiring preoperative localization of the detected lesions. Developing an individual‐specific breast biomechanical model capable of simulating these deformations remains challenging yet highly desirable. This study presents a novel approach that combines finite element analysis with the optimization of mechanical properties of breast tissues, using only surface information to construct a personalized deformation model of the breast. A visco‐hyperelastic model is employed to characterize the stress–strain relationship of breast tissue. The proposed method has been tested on 15 cases of breast cancer and achieves a tumor localization error of 8.12 ± 4.15 mm. The results show that this approach provides an accurate and realistic estimation of large breast tissue deformations and yields smaller tumor localization errors compared to previously reported methods.","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"43 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144594116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Ex vivo single‐cell profiling of acute myocardial infarction patients reveals disproportionate CD66b+ cell secretion response 急性心肌梗死患者的体外单细胞谱显示不成比例的CD66b+细胞分泌反应

IF 7.4 2区医学

Bioengineering & Translational Medicine Pub Date : 2025-07-07 DOI: 10.1002/btm2.70043

Kerwin Kwek Zeming, Ri Lu, Elizabeth Lee, Ka‐Wai Cheung, Nicholas W. S. Chew, Kai Lee Woo, Lih Feng Cheow, Jongyoon Han, Shir Lynn Lim

{"title":"Ex vivo single‐cell profiling of acute myocardial infarction patients reveals disproportionate CD66b+ cell secretion response","authors":"Kerwin Kwek Zeming, Ri Lu, Elizabeth Lee, Ka‐Wai Cheung, Nicholas W. S. Chew, Kai Lee Woo, Lih Feng Cheow, Jongyoon Han, Shir Lynn Lim","doi":"10.1002/btm2.70043","DOIUrl":"https://doi.org/10.1002/btm2.70043","url":null,"abstract":"Acute myocardial infarction (AMI), a leading cause of death globally, triggers complex inflammatory responses critical to patient outcomes. However, rapid tools for profiling immune responses at the single‐cell level are lacking. The integrated Single‐cell Enzyme and Antigen Quantification (iSEAQ) system addresses this gap by enabling high‐throughput, single‐cell analysis of immune cell activity using just 20 μL of blood. This novel tool processes live CD66b and CD3 cells to quantify the secretion of Granzyme B, Neutrophil Elastase, and CD31 within minutes. Longitudinal studies on nine AMI patients revealed that CD66b+ cells are major contributors (up to 95%) to key inflammatory enzymes, including the unexpected secretion of Granzyme B. iSEAQ achieves unparalleled sensitivity (0.4 fg/cell) and predictive accuracy (>90%) for patient profiling across AMI onset, treatment, and discharge. This innovation provides clinicians with a rapid, precise method to monitor immune responses, unveiling new insights into AMI inflammation and therapy.","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"43 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144577990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Hypoxia‐preconditioned MiotEVs from bone marrow mesenchymal stem cells inhibit myocardial infarction‐induced cardiac fibrosis 来自骨髓间充质干细胞的缺氧预处理miotev抑制心肌梗死诱导的心脏纤维化

IF 7.4 2区医学

Bioengineering & Translational Medicine Pub Date : 2025-07-04 DOI: 10.1002/btm2.70046

Jungang Nie, Hongwen Zhu, Zhiming Gao, Liang Wang

{"title":"Hypoxia‐preconditioned MiotEVs from bone marrow mesenchymal stem cells inhibit myocardial infarction‐induced cardiac fibrosis","authors":"Jungang Nie, Hongwen Zhu, Zhiming Gao, Liang Wang","doi":"10.1002/btm2.70046","DOIUrl":"https://doi.org/10.1002/btm2.70046","url":null,"abstract":"Hypoxia‐preconditioned bone marrow mesenchymal stem cell‐derived mitochondrial extracellular vesicles (Hypoxia‐BMSC MitoEVs) emerged as a novel therapeutic candidate for myocardial infarction (MI)‐induced cardiac fibrosis. Here, we demonstrate that MitoEVs isolated from hypoxic BMSCs, rich in intact mitochondria and the RNA‐binding protein Quaking (QKI), potently inhibited TGF‐β1‐driven myofibroblast activation in vitro by suppressing α‐SMA and collagen expression while restoring mitochondrial oxidative phosphorylation and metabolic balance. In a murine MI model, systemic delivery of Hypoxia‐BMSC MitoEVs attenuated cardiac fibrosis, reduced infarct size, and improved left ventricular function. Pharmacological inhibition of mitochondrial ATP synthase in MitoEVs similarly diminished their therapeutic efficacy. Mechanistically, MitoEVs delivered QKI protein to cardiac fibroblasts, where it inhibited translation of fibrotic mRNAs via m7G‐modified RNA interactions. Genetic ablation of QKI in BMSCs abrogated MitoEV‐mediated antifibrotic effects both in vitro and in vivo, confirming QKI as a critical effector. These results suggested that both QKI‐driven translational suppression and mitochondrial bioenergetics underpin their antifibrotic action. These findings highlight Hypoxia‐BMSC MitoEVs as a therapeutic strategy to mitigate post‐MI fibrosis, warranting further exploration for clinical translation.","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"42 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144566559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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