Bioengineering & Translational Medicine最新文献_第10页

Photothermal Prussian blue nanoparticles generate potent multi-targeted tumor-specific T cells as an adoptive cell therapy 光热普鲁士蓝纳米粒子可产生强效多靶点肿瘤特异性 T 细胞，作为一种采用性细胞疗法

IF 7.4 2区医学

Bioengineering & Translational Medicine Pub Date : 2023-12-22 DOI: 10.1002/btm2.10639

Elizabeth E. Sweeney, Palak Sekhri, Nethaji Muniraj, Jie Chen, Sally Feng, Joshua Terao, Samantha J. Chin, Danielle E. Schmidt, Catherine M. Bollard, Conrad Russell Y. Cruz, Rohan Fernandes

{"title":"Photothermal Prussian blue nanoparticles generate potent multi-targeted tumor-specific T cells as an adoptive cell therapy","authors":"Elizabeth E. Sweeney, Palak Sekhri, Nethaji Muniraj, Jie Chen, Sally Feng, Joshua Terao, Samantha J. Chin, Danielle E. Schmidt, Catherine M. Bollard, Conrad Russell Y. Cruz, Rohan Fernandes","doi":"10.1002/btm2.10639","DOIUrl":"10.1002/btm2.10639","url":null,"abstract":"Prussian blue nanoparticle-based photothermal therapy (PBNP-PTT) is an effective tumor treatment capable of eliciting an antitumor immune response. Motivated by the ability of PBNP-PTT to potentiate endogenous immune responses, we recently demonstrated that PBNP-PTT could be used ex vivo to generate tumor-specific T cells against glioblastoma (GBM) cell lines as an adoptive T cell therapy (ATCT). In this study, we further developed this promising T cell development platform. First, we assessed the phenotype and function of T cells generated using PBNP-PTT. We observed that PBNP-PTT facilitated CD8+ T cell expansion from healthy donor PBMCs that secreted IFNγ and TNFα and upregulated CD107a in response to engagement with target U87 cells, suggesting specific antitumor T cell activation and degranulation. Further, CD8+ effector and effector memory T cell populations significantly expanded after co-culture with U87 cells, consistent with tumor-specific effector responses. In orthotopically implanted U87 GBM tumors in vivo, PBNP-PTT-derived T cells effectively reduced U87 tumor growth and generated long-term survival in >80% of tumor-bearing mice by Day 100, compared to 0% of mice treated with PBS, non-specific T cells, or T cells expanded from lysed U87 cells, demonstrating an enhanced antitumor efficacy of this ATCT platform. Finally, we tested the generalizability of our approach by generating T cells targeting medulloblastoma (D556), breast cancer (MDA-MB-231), neuroblastoma (SH-SY5Y), and acute monocytic leukemia (THP-1) cell lines. The resulting T cells secreted IFNγ and exerted increased tumor-specific cytolytic function relative to controls, demonstrating the versatility of PBNP-PTT in generating tumor-specific T cells for ATCT.","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"9 3","pages":""},"PeriodicalIF":7.4,"publicationDate":"2023-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/btm2.10639","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138943480","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

Fibroblasts and endothelial cells interplay drives hypertrophic scar formation: Insights from in vitro and in vivo models 成纤维细胞和内皮细胞的相互作用推动了肥厚性疤痕的形成：体外和体内模型的启示

IF 7.4 2区医学

Bioengineering & Translational Medicine Pub Date : 2023-12-20 DOI: 10.1002/btm2.10630

Yaxin Tan, Mengde Zhang, Yi Kong, Fanliang Zhang, Yuzhen Wang, Yuyan Huang, Wei Song, Zhao Li, Linhao Hou, Liting Liang, Xu Guo, Qinghua Liu, Yu Feng, Chao Zhang, Xiaobing Fu, Sha Huang

{"title":"Fibroblasts and endothelial cells interplay drives hypertrophic scar formation: Insights from in vitro and in vivo models","authors":"Yaxin Tan, Mengde Zhang, Yi Kong, Fanliang Zhang, Yuzhen Wang, Yuyan Huang, Wei Song, Zhao Li, Linhao Hou, Liting Liang, Xu Guo, Qinghua Liu, Yu Feng, Chao Zhang, Xiaobing Fu, Sha Huang","doi":"10.1002/btm2.10630","DOIUrl":"10.1002/btm2.10630","url":null,"abstract":"Hypertrophic scar formation is influenced by the intricate interplay between fibroblasts and endothelial cells. In this study, we investigated this relationship using in vitro and in vivo models. Clinical observations revealed distinct morphological changes and increased vascularity at pathological scar sites. Further analysis using OCTA, immunohistochemistry, and immunofluorescence confirmed the involvement of angiogenesis in scar formation. Our indirect co-culture systems demonstrated that endothelial cells enhance the proliferation and migration of fibroblasts through the secretion of cytokines including VEGF, PDGF, bFGF, and TGF-β. Additionally, a suspended co-culture multicellular spheroid model revealed molecular-level changes associated with extracellular matrix remodeling, cellular behaviors, inflammatory response, and pro-angiogenic activity. Furthermore, KEGG pathway analysis identified the involvement of TGF-β, IL-17, Wnt, Notch, PI3K-Akt, and MAPK pathways in regulating fibroblasts activity. These findings underscore the critical role of fibroblasts-endothelial cells crosstalk in scar formation and provide potential targets for therapeutic intervention. Understanding the molecular mechanisms underlying this interplay holds promise for the development of innovative approaches to treat tissue injuries and diseases.","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"9 2","pages":""},"PeriodicalIF":7.4,"publicationDate":"2023-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/btm2.10630","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138823290","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

A bioengineered anti-VEGF protein with high affinity and high concentration for intravitreal treatment of wet age-related macular degeneration 一种高亲和力、高浓度的生物工程抗血管内皮生长因子蛋白，用于玻璃体内治疗湿性老年性黄斑变性

IF 7.4 2区医学

Bioengineering & Translational Medicine Pub Date : 2023-12-19 DOI: 10.1002/btm2.10632

Chengnan Huang, Yuelin Wang, Jinliang Huang, Huiqin Liu, Zhidong Chen, Yang Jiang, Youxin Chen, Feng Qian

{"title":"A bioengineered anti-VEGF protein with high affinity and high concentration for intravitreal treatment of wet age-related macular degeneration","authors":"Chengnan Huang, Yuelin Wang, Jinliang Huang, Huiqin Liu, Zhidong Chen, Yang Jiang, Youxin Chen, Feng Qian","doi":"10.1002/btm2.10632","DOIUrl":"10.1002/btm2.10632","url":null,"abstract":"Intravitreal (IVT) injection of anti-vascular endothelial growth factor (anti-VEGF) has greatly improved the treatment of many retinal disorders, including wet age-related macular degeneration (wAMD), which is the third leading cause of blindness. However, frequent injections can be difficult for patients and may lead to various risks such as elevated intraocular pressure, infection, and retinal detachment. To address this issue, researchers have found that IVT injection of anti-VEGF proteins at their maximally viable concentration and dose can be an effective strategy. However, the intrinsic protein structure can limit the maximum concentration due to stability and solution viscosity. To overcome this challenge, we developed a novel anti-VEGF protein called nanoFc by fusing anti-VEGF nanobodies with a crystallizable fragment (Fc). NanoFc has demonstrated high binding affinity to VEGF165 through multivalency and potent bioactivity in various bioassays. Furthermore, nanoFc maintains satisfactory chemical and physical stability at 4°C over 1 month and is easily injectable at concentrations up to 200 mg/mL due to its unique architecture that yields a smaller shape factor. The design of nanoFc offers a bioengineering strategy to ensure both strong anti-VEGF binding affinity and high protein concentration, with the goal of reducing the frequency of IV injections.","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"9 2","pages":""},"PeriodicalIF":7.4,"publicationDate":"2023-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/btm2.10632","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138823284","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

Efficacy of catheter-based drug delivery in a hybrid in vitro model of cardiac microvascular obstruction with porcine microthrombi 在猪微血栓心脏微血管阻塞混合体外模型中导管给药的功效

IF 7.4 2区医学

Bioengineering & Translational Medicine Pub Date : 2023-12-08 DOI: 10.1002/btm2.10631

Yannick Rösch, Thorald Stolte, Miriam Weisskopf, Sabrina Frey, Rob Schwartz, Nikola Cesarovic, Dominik Obrist

{"title":"Efficacy of catheter-based drug delivery in a hybrid in vitro model of cardiac microvascular obstruction with porcine microthrombi","authors":"Yannick Rösch, Thorald Stolte, Miriam Weisskopf, Sabrina Frey, Rob Schwartz, Nikola Cesarovic, Dominik Obrist","doi":"10.1002/btm2.10631","DOIUrl":"10.1002/btm2.10631","url":null,"abstract":"Microvascular obstruction (MVO) often occurs in ST-elevation myocardial infarction (STEMI) patients after percutaneous coronary intervention (PCI). Diagnosis and treatment of MVO lack appropriate and established procedures. This study focused on two major points by using an in vitro multiscale flow model, which comprised an aortic root model with physiological blood flow and a microfluidic model of the microcirculation with vessel diameters down to 50 μm. First, the influence of porcine microthrombi (MT), injected into the fluidic microchip, on perfusion was investigated. We found that only <math>\u0000 <mrow>\u0000 <mn>43</mn>\u0000 <mo>%</mo>\u0000 </mrow></math> of all injected MT were fully occlusive. Second, it could also be shown that the maximal concentration of a dye (representing therapeutic agent) during intracoronary infusion could be increased on average by <math>\u0000 <mrow>\u0000 <mn>58</mn>\u0000 <mo>%</mo>\u0000 </mrow></math>, when proximally occluding the coronary artery by a balloon during drug infusion. The obtained results and insights enhance the understanding of perfusion in MVO-affected microcirculation and could lead to improved treatment methods for MVO patients.","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"9 2","pages":""},"PeriodicalIF":7.4,"publicationDate":"2023-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/btm2.10631","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138551153","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

Immunogenicity of an adjuvanted broadly active influenza vaccine in immunocompromised and diverse populations 广谱活性流感佐剂疫苗在免疫力低下和不同人群中的免疫原性

IF 7.4 2区医学

Bioengineering & Translational Medicine Pub Date : 2023-12-08 DOI: 10.1002/btm2.10634

Dylan A. Hendy, Erik S. Pena, Luis Ontiveros-Padilla, Timothy A. Dixon, Denzel D. Middleton, Grace L. Williamson, Nicole Rose Lukesh, Sean R. Simpson, Rebeca T. Stiepel, Md Jahirul Islam, Michael A. Carlock, Ted M. Ross, Eric M. Bachelder, Kristy M. Ainslie

{"title":"Immunogenicity of an adjuvanted broadly active influenza vaccine in immunocompromised and diverse populations","authors":"Dylan A. Hendy, Erik S. Pena, Luis Ontiveros-Padilla, Timothy A. Dixon, Denzel D. Middleton, Grace L. Williamson, Nicole Rose Lukesh, Sean R. Simpson, Rebeca T. Stiepel, Md Jahirul Islam, Michael A. Carlock, Ted M. Ross, Eric M. Bachelder, Kristy M. Ainslie","doi":"10.1002/btm2.10634","DOIUrl":"10.1002/btm2.10634","url":null,"abstract":"Influenza virus outbreaks are a major burden worldwide each year. Current vaccination strategies are inadequate due to antigenic drift/shift of the virus and the elicitation of low immune responses. The use of computationally optimized broadly reactive antigen (COBRA) hemagglutinin (HA) immunogens subvert the constantly mutating viruses; however, they are poorly immunogenic on their own. To increase the immunogenicity of subunit vaccines such as this, adjuvants can be delivered with the vaccine. For example, agonists of the stimulator of interferon genes (STING) have proven efficacy as vaccine adjuvants. However, their use in high-risk populations most vulnerable to influenza virus infection has not been closely examined. Here, we utilize a vaccine platform consisting of acetalated dextran microparticles loaded with COBRA HA and the STING agonist cyclic GMP-AMP. We examine the immunogenicity of this platform in mouse models of obesity, aging, and chemotherapy-induced immunosuppression. Further, we examine vaccine efficacy in collaborative cross mice, a genetically diverse population that mimics human genetic heterogeneity. Overall, this vaccine platform had variable efficacy in these populations supporting work to better tailor adjuvants to specific populations.","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"9 2","pages":""},"PeriodicalIF":7.4,"publicationDate":"2023-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/btm2.10634","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138551141","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

Development of a multifunctional bioreactor to evaluate the promotion effects of cyclic stretching and electrical stimulation on muscle differentiation 多功能生物反应器的开发，以评估循环拉伸和电刺激对肌肉分化的促进作用

IF 7.4 2区医学

Bioengineering & Translational Medicine Pub Date : 2023-12-07 DOI: 10.1002/btm2.10633

Wei-Wen Hu, Yen-Chi Chen, Chia-Wen Tsao, Shen-Liang Chen, Chung-Yuh Tzeng

{"title":"Development of a multifunctional bioreactor to evaluate the promotion effects of cyclic stretching and electrical stimulation on muscle differentiation","authors":"Wei-Wen Hu, Yen-Chi Chen, Chia-Wen Tsao, Shen-Liang Chen, Chung-Yuh Tzeng","doi":"10.1002/btm2.10633","DOIUrl":"10.1002/btm2.10633","url":null,"abstract":"A multifunctional bioreactor was fabricated in this study to investigate the facilitation efficiency of electrical and mechanical stimulations on myogenic differentiation. This bioreactor consisted of a highly stretchable conductive membrane prepared by depositing polypyrrole (PPy) on a flexible polydimethylsiloxane (PDMS) film. The tensile deformation of the PPy/PDMS membrane can be tuned by adjusting the channel depth. In addition, PPy/PDMS maintained its electrical conductivity under continuous cyclic stretching in the strain range of 6.5%–13% for 24 h. This device can be used to individually or simultaneously perform cyclic stretching and electrical stimulation. The results of single stimulation showed that either cyclic stretching or electrical stimulation upregulated myogenic gene expression and promoted myotube formation, where electrical stimulation improved better than cyclic stretching. However, only cyclic stretching can align C2C12 cells perpendicular to the stretching direction, and electrical stimulation did not affect cell morphology. Myosin heavy chain (MHC) immunostaining demonstrated that oriented cells under cyclic stretching resulted in parallel myotubes. The combination of these two stimuli exhibited synergetic effects on both myogenic gene regulation and myotube formation, and the incorporated electrical field did not affect the orientation effect of the cyclic stretching. These results suggested that these two treatments likely influenced cells through different pathways. Overall, the simultaneous application of cyclic stretching and electrical stimulation preserved both stimuli's advantages, so myo-differentiation can be highly improved to obtain abundant parallel myotubes, suggesting that our developed multifunctional bioreactor should benefit muscle tissue engineering applications.","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"9 2","pages":""},"PeriodicalIF":7.4,"publicationDate":"2023-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/btm2.10633","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138544913","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

Establishment of bladder cancer spheroids and cultured in microfluidic platform for predicting drug response 建立膀胱癌球体并在微流控平台中培养，以预测药物反应

IF 7.4 2区医学

Bioengineering & Translational Medicine Pub Date : 2023-12-04 DOI: 10.1002/btm2.10624

Qiao Xiong, Ting Liu, Yidie Ying, Xiaowen Yu, Ziwei Wang, Hongliang Gao, Tianhai Lin, Weihua Fan, Zhensheng Zhang, Qiang Wei, Yuqing Ge, Shuxiong Zeng, Chuanliang Xu

{"title":"Establishment of bladder cancer spheroids and cultured in microfluidic platform for predicting drug response","authors":"Qiao Xiong, Ting Liu, Yidie Ying, Xiaowen Yu, Ziwei Wang, Hongliang Gao, Tianhai Lin, Weihua Fan, Zhensheng Zhang, Qiang Wei, Yuqing Ge, Shuxiong Zeng, Chuanliang Xu","doi":"10.1002/btm2.10624","DOIUrl":"10.1002/btm2.10624","url":null,"abstract":"Cisplatin-containing combination chemotherapy has been used as the standard treatment for bladder cancer patients at advanced stage. However, nearly 50% of patients are nonresponders. To guide the selection of more effective chemotherapeutic agents, a bladder cancer spheroids microfluidic drug sensitivity analysis system was established in this study. Bladder cancer spheroids were established and successfully cultured in a customized microfluidic device to assess their response to different chemotherapeutic agents. The in vitro drug sensitivity results were also compared to patient-derived xenograft (PDX) models and clinical responses of patients. As a result, bladder cancer spheroids faithfully recapitulate the histopathological and genetic features of their corresponding parental tumors. Furthermore, the in vitro drug sensitivity outcomes of spheroids (n = 8) demonstrated a high level of correlation with the PDX (n = 2) and clinical response in patients (n = 2). Our study highlights the potential of combining bladder cancer spheroids and microfluidic devices as an efficient and accurate platform for personalized selection of chemotherapeutic agents.","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"9 2","pages":""},"PeriodicalIF":7.4,"publicationDate":"2023-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/btm2.10624","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138485915","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

Advances in high throughput cell culture technologies for therapeutic screening and biological discovery applications 用于治疗筛选和生物发现应用的高通量细胞培养技术的进步

IF 7.4 2区医学

Bioengineering & Translational Medicine Pub Date : 2023-12-04 DOI: 10.1002/btm2.10627

Hyeon Ryoo, Hannah Kimmel, Evi Rondo, Gregory H. Underhill

{"title":"Advances in high throughput cell culture technologies for therapeutic screening and biological discovery applications","authors":"Hyeon Ryoo, Hannah Kimmel, Evi Rondo, Gregory H. Underhill","doi":"10.1002/btm2.10627","DOIUrl":"10.1002/btm2.10627","url":null,"abstract":"Cellular phenotypes and functional responses are modulated by the signals present in their microenvironment, including extracellular matrix (ECM) proteins, tissue mechanical properties, soluble signals and nutrients, and cell–cell interactions. To better recapitulate and analyze these complex signals within the framework of more physiologically relevant culture models, high throughput culture platforms can be transformative. High throughput methodologies enable scientists to extract increasingly robust and broad datasets from individual experiments, screen large numbers of conditions for potential hits, better qualify and predict responses for preclinical applications, and reduce reliance on animal studies. High throughput cell culture systems require uniformity, assay miniaturization, specific target identification, and process simplification. In this review, we detail the various techniques that researchers have used to face these challenges and explore cellular responses in a high throughput manner. We highlight several common approaches including two-dimensional multiwell microplates, microarrays, and microfluidic cell culture systems as well as unencapsulated and encapsulated three-dimensional high throughput cell culture systems, featuring multiwell microplates, micromolds, microwells, microarrays, granular hydrogels, and cell-encapsulated microgels. We also discuss current applications of these high throughput technologies, namely stem cell sourcing, drug discovery and predictive toxicology, and personalized medicine, along with emerging opportunities and future impact areas.","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"9 3","pages":""},"PeriodicalIF":7.4,"publicationDate":"2023-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/btm2.10627","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138485918","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

Therapeutic potential of mesenchymal stem cells from human iPSC-derived teratomas for osteochondral defect regeneration 人间充质干细胞衍生畸胎瘤对骨软骨缺损再生的治疗潜力

IF 7.4 2区医学

Bioengineering & Translational Medicine Pub Date : 2023-11-29 DOI: 10.1002/btm2.10629

Jiseong Kim, Jin-Su Kim, Dohyun Kim, Alvin Bacero Bello, Byoung Ju Kim, Byung-Hyun Cha, Soo-Hong Lee

{"title":"Therapeutic potential of mesenchymal stem cells from human iPSC-derived teratomas for osteochondral defect regeneration","authors":"Jiseong Kim, Jin-Su Kim, Dohyun Kim, Alvin Bacero Bello, Byoung Ju Kim, Byung-Hyun Cha, Soo-Hong Lee","doi":"10.1002/btm2.10629","DOIUrl":"10.1002/btm2.10629","url":null,"abstract":"Human induced pluripotent stem cells (iPSCs) hold great promise for personalized medicine, as they can be differentiated into specific cell types, especially mesenchymal stem cells (MSCs). Therefore, our study sought to assess the feasibility of deriving MSCs from teratomas generated from human iPSCs. Teratomas serve as a model to mimic multilineage human development, thus enriching specific somatic progenitors and stem cells. Here, we discovered a small, condensed mass of MSCs within iPSC-generated teratomas. Afterward, we successfully isolated MSCs from this condensed mass, which was a byproduct of teratoma development. To evaluate the characteristics and cell behaviors of iPSC-derived MSCs (iPSC-MSCs), we conducted comprehensive assessments using qPCR, immunophenotype analysis, and cell proliferation-related assays. Remarkably, iPSC-MSCs exhibited an immunophenotype resembling that of conventional MSCs, and they displayed robust proliferative capabilities, similar to those of higher pluripotent stem cell-derived MSCs. Furthermore, iPSC-MSCs demonstrated the ability to differentiate into multiple lineages in vitro. Finally, we evaluated the therapeutic potential of iPSC-MSCs using an osteochondral defect model. Our findings demonstrated that teratomas are a promising source for the isolation of condensed MSCs. More importantly, our results suggest that iPSC-MSCs derived from teratomas possess the capacity for tissue regeneration, highlighting their promise for future therapeutic applications.","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"9 2","pages":""},"PeriodicalIF":7.4,"publicationDate":"2023-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/btm2.10629","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138455890","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

First magnetic particle imaging to assess pulmonary vascular leakage in vivo in the acutely injured and fibrotic lung 首次磁颗粒成像评估急性损伤和纤维化肺的肺血管渗漏

IF 7.4 2区医学

Bioengineering & Translational Medicine Pub Date : 2023-11-29 DOI: 10.1002/btm2.10626

Xin Feng, Pengli Gao, Yabin Li, Hui Hui, Jingying Jiang, Fei Xie, Jie Tian

{"title":"First magnetic particle imaging to assess pulmonary vascular leakage in vivo in the acutely injured and fibrotic lung","authors":"Xin Feng, Pengli Gao, Yabin Li, Hui Hui, Jingying Jiang, Fei Xie, Jie Tian","doi":"10.1002/btm2.10626","DOIUrl":"10.1002/btm2.10626","url":null,"abstract":"Increased pulmonary vascular permeability is a characteristic feature of lung injury. However, there are no established methods that allow the three-dimensional visualization and quantification of pulmonary vascular permeability in vivo. Evans blue extravasation test and total protein test of bronchoalveolar lavage fluid (BALF) are permeability assays commonly used in research settings. However, they lack the ability to identify the spatial and temporal heterogeneity of endothelial barrier disruption, which is typical in lung injuries. Magnetic resonance (MR) and near-infrared (NIR) imaging have been proposed to image pulmonary permeability, but suffer from limited sensitivity and penetration depth, respectively. In this study, we report the first use of magnetic particle imaging (MPI) to assess pulmonary vascular leakage noninvasively in vivo in mice. A dextran-coated superparamagnetic iron oxide (SPIO), synomag®, was employed as the imaging tracer, and pulmonary SPIO extravasation was imaged and quantified to evaluate the vascular leakage. Animal models of acute lung injury and pulmonary fibrosis (PF) were used to validate the proposed method. MPI sensitively detected the SPIO extravasation in both acutely injured and fibrotic lungs in vivo, which was confirmed by ex vivo imaging and Prussian blue staining. Moreover, 3D MPI illustrated the spatial heterogeneity of vascular leakage, which correlated well with CT findings. Based on the in vivo 3D MPI images, we defined the SPIO extravasation index (SEI) to quantify the vascular leakage. A significant increase in SEI was observed in the injured lungs, in consistent with the results obtained via ex vivo permeability assays. Overall, our results demonstrate that 3D quantitative MPI serves as a useful tool to examine pulmonary vascular integrity in vivo, which shows promise for future clinical translation.","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"9 2","pages":""},"PeriodicalIF":7.4,"publicationDate":"2023-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/btm2.10626","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138455891","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