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Tryptophan 2,3-dioxygenase-positive matrix fibroblasts fuel breast cancer lung metastasis via kynurenine-mediated ferroptosis resistance of metastatic cells and T cell dysfunction

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Cancer Communications 2024年第11期44卷 1261-1286页

作者： Yongcan Liu Shanchun Chen Xueying Wan Rui Wang haojun Luo Chao Chang Peijin Dai Yubi Gan Yuetong Guo Yixuan hou Yan Sun Yong Teng Xiaojiang Cui Manran Liu Key Laboratory of Laboratory Medical Diagnostics Chinese Ministry of EducationChongqing Medical UniversityChongqingP.R.China department of Thyroid and Breast Surgery The Second Affiliated Hospital of Chongqing Medical UniversityChongqingP.R.China Experimental Teaching Center of Basic Medicine Science Chongqing Medical UniversityChongqingP.R.China department of Cell Biology and Medical Genetics Basic Medical SchoolChongqing Medical UniversityChongqingP.R.China department of hematology and Medical Oncology Winship Cancer InstituteEmory University School of MedicineAtlantaGeorgiaUSA wallace h.coulter department of biomedical engineering Georgia Institute of Technology and Emory UniversityAtlantaGeorgiaUSA department of Surgery Department of Obstetrics and GynecologySamuel Oschin Comprehensive Cancer InstituteCedars-Sinai Medical CenterLos AngelesCaliforniaUSA

Background:Tumor metastasis is a major threat to cancer patient *** organ-specific niche plays a pivotal role in tumor organotropic *** serve as a vital component of the metastatic microenviron-ment,but how heterogeneous metastasis-associated fibroblasts(MAFs)promote organotropic metastasis is poorly ***,we aimed to decipher the heterogeneity of MAFs and elucidate the distinct roles of these fibroblasts in pulmonary metastasis formation in breast ***:Mouse models of breast cancer pulmonary metastasis were estab-lished using an in vivo selection method of repeated injections of metastatic cells purified from the mouse ***-cell RNA-sequencing(scRNA-seq)was employed to investigate the heterogeneity of *** mice were used to examine the contribution of tryptophan 2,3-dioxygenase-positive matrix fibroblasts(TDO2^(+)MFs)in lung ***:We uncovered 3 subtypes of MAFs in the lung metastatic microenviron-ment,and their transcriptome profiles changed dynamically as lung metastasis *** the predominant subtype,MFs were exclusively marked by platelet-derived growth factor receptor alpha(PDGFRA)and mainly located on the edge of the metastasis,and T cells were enriched around ***,high MF sig-natures were significantly associated with poor survival in breast cancer *** metastases were markedly diminished,and the suppression of T cells was dramatically attenuated in MF-depleted experimental metastatic mouse *** found that TDO2^(+)MFs controlled pulmonary metastasis by producing kynurenine(KYN),which upregulated ferritin heavy chain 1(FTh1)level in dis-seminated tumor cells(DTCs),enabling DTCs to resist ***,TDO2^(+)MF-secreted chemokines C-C motif chemokine ligand 8(CCL8)and C-C motif chemokine ligand 11(CCL11)recruited T ***2^(+)MF-derived KYN induced T cell *** knockout of Tdo2 in MFs diminished lung metastasis and enhanced

关键词： Matrix fibroblasts Lung metastasis Tryptophan 2 3-dioxygenase T cell dysfunction Ferropto-sis

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Advances in sensor developments for cell culture monitoring

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BMEMat(biomedical engineering Materials) 2023年第4期1卷 4-28页

作者： Ka Ram Kim Woon-hong Yeo George W.Woodruff School of Mechanical engineering Georgia Institute of TechnologyAtlantaGeorgiaUSA IEN Center for human-Centric Interfaces and engineering Institute for Electronics and NanotechnologyGeorgia Institute of TechnologyAtlantaGeorgiaUSA wallace h.coulter department of biomedical engineering Georgia Tech and Emory University School of MedicineAtlantaGeorgiaUSA Institute for Materials Institute for Robotics and Intelligent MachinesNeural Engineering CenterGeorgia Institute of TechnologyAtlantaGeorgiaUSA

Cell culture encompasses procedures for extracting cells from their natural tissue and cultivating them under controlled artificial conditions. During this process, various factors, including cell physiological/morphological properties, culture environments, metabolites, and contaminants, have to be precisely controlled and monitored for the survival of cells and the pursuit of the desired properties of the cells. This review summarizes recent advances in sensor technologies and manufacturing strategies for various cell culture platforms using traditional plastics, microfluidic chips, and scalable bioreactors. We share the details of newly developed biological sensors, chemical sensors, optical sensors, electronic chip technologies, and material integration methods. The precise control of parameters based on the feedback by these sensors and electronics enhances cell culture quality and throughput.

关键词： biosensor cell culture monitoring cell physiology monitoring electrochemical sensing metabolite optical sensing

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基于多尺度计算方法的活体磁共振谱自动相位矫正和代谢物定量分析(英文)

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波谱学杂志 2014年第1期31卷 32-39页

作者：张晓东胡小平 Yerkes Imaging Center and Division of Neuropharmacology and Neurologic Diseases Yerkes National Primate Research Center Emory University biomedical Imaging Technique Center The Wallace H. Coulter Department of Biomedical EngineeringEmory University and Georgia Institute of Technology

活体多片磁共振谱成像(MRSI)产生大量的波谱数据,因此需要使用自动的谱数据分析方法来获得不同组织代谢产物的定量分布图.然而,活体波谱通常产生严重的谱和基线变形,使得基于曲线拟合的谱定量数据分析方法失效.该文应用多尺度分析(Multi... 详细信息

活体多片磁共振谱成像(MRSI)产生大量的波谱数据,因此需要使用自动的谱数据分析方法来获得不同组织代谢产物的定量分布图.然而,活体波谱通常产生严重的谱和基线变形,使得基于曲线拟合的谱定量数据分析方法失效.该文应用多尺度分析(Multiscale)方法自动确定兴趣代谢物在频率空间的谱峰特征(位置和线宽),然后通过叠代运算对该代谢物对应的谱峰进行独立的自动相位矫正和线型拟合.大脑波谱成像的实验结果表明,该方法可以方便、有效的获得代谢产物在大脑的分布,特别适宜于多片磁共振谱成像的代谢产物定量分析.

关键词：活体多片磁共振谱成像(MRSI) 多尺度分析方法线型拟合自动相位矫正

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Additive manufacturing of high aspect-ratio structures with self-focusing photopolymerization

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Light(Advanced Manufacturing) 2022年第3期3卷 120-149页

作者： Mingyu Yang Kavin Kowsari Nia O.Myrie Daniela Espinosa-hoyos Anna Jagielska Seok Kim Nicholas X.Fang Krystyn J.Van Vliet harvard-MIT health Sciences and Technology Massachusetts Institute of TechnologyCambridgeMA02139United States department of Mechanical engineering Massachusetts Institute of TechnologyCambridgeMA02139United States department of Radiology Brigham and Women’s HospitalHarvard Medical SchoolBostonMA02115United States department of Biological engineering Massachusetts Institute of TechnologyCambridgeMA02139United States Walter h.coulter department of biomedical engineering Georgia Institute of Technology and Emory University School of MedicineAtlantaGA30332United States department of Chemical engineering Massachusetts Institute of TechnologyCambridgeMA02139United States department of Materials Science&engineering Massachusetts Institute of TechnologyCambridgeMA02139United States department of Mechanical engineering Changwon National UniversityChangwon51140South Korea

Photocrosslinkable polymers have been exploited to attain impressive advantages in printing freestanding,micrometer-scale,mechanically compliant ***,a more integrated understanding of both the polymer photochemistry and the microfabrication processes could enable new strategic design avenues,unlocking far-reaching applications of the light-based modality of additive *** promising approach for achieving high-aspect-ratio structures is to leverage the phenomenon of light self-trapping during the photopolymerization *** this review,we discuss the design of materials that facilitate this optical behavior,the computational modeling and practical processing considerations to achieve high aspect-ratio structures,and the range of applications that can benefit from architectures fabricated using light self-trapping-especially those demanding free-standing structures and materials of stiffnesses relevant in biological *** interactions exist among material attributes,including polymer composition,and processing parameters such as light *** identify strong opportunities for predictive design of both the material and the ***,this perspective describes the wide range of existing polymers and additive manufacturing approaches,and highlights various future directions to enable constructs with new complexities and functionalities through the development of next-generation photocrosslinkable materials and micromanufacturing methods.

关键词： Additive manufacturing Optical waveguide high aspect-ratio Biocompatible structures Polymer photochemistry

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Ultrasound-mediated drug-free theranostics for treatment of prostate cancer

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Bioactive Materials 2024年第5期35卷 45-55页

作者： Reshani himashika Perera Felipe Matias Berg Eric Chua Abenojar Pinunta Nittayacharn Youjoung Kim Xinning Wang James Peter Basilion Agata Exner department of Radiology Case Western Reserve UniversityClevelandOH44106USA hospital Israelita Albert Einstein S˜ao PauloSP05652-900Brazil department of biomedical engineering Faculty of EngineeringMahidol UniversityPuttamonthonNakorn Pathom73170Thailand department of biomedical engineering Case Western Reserve UniversityCleveland44106OHUSA

Lipid-shelled nanobubbles(NBs)can be visualized and activated using noninvasive ultrasound(US)stimulation,leading to significant *** work demonstrates that active targeting of NBs to prostate-specific membrane antigen(PSMA)overexpressed in prostate cancer(PCa)results in enhanced cellular internalization and prolongs NB retention with persistent,cancer-cell specific acoustic *** this work,we hypothesized that tumor-accumulated PSMA-NBs combined with low frequency unfocused therapeutic US(TUS)will lead to selective damage and induce a specific therapeutic effect in PSMA-expressing tumors compared to PSMA-negative *** observed that the internalized NBs and cellular compartments were disrupted after the PSMA-NB+TUS(targeted NB therapy or TNT)application,yet treated cells remained intact and *** vivo,PSMA-expressing tumors in mice receiving TNT treatment demonstrated a significantly greater extent of apoptosis(78.4±9.3%,phibited the PSMA expressing tumor growth and increased median survival time by 103%,photopic rabbit PCa *** demonstrate that cavitation of PSMA-NBs internalized via receptor-mediated endocytosis into target PCa cells using unfocused ultrasound results in significant,tumor-specific *** effects,while not lethal to PSMA-expressing cancer cells in vitro,result in significant in vivo reduction in tumor progression in two models of *** the mechanism of action of these effects is yet unclear,it is likely related to a locally-induced immune response,opening the door to future investigations in this area.

关键词： Nanobubbles PC-3 Cells Contrast enhanced ultrasound Prostate-specific membrane antigen(PSMA) Ultrasound-mediated therapy

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Differentiation of human mesenchymal stem cell spheroids under microgravity conditions

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Cell Regeneration 2012年第1期1卷 2-10页

作者： Wolfgang h Cerwinka Starlette M Sharp Barbara D Boyan haiyen E Zhau Leland W K Chung Clayton Yates Children’s healthcare of Atlanta Emory University School of Medicine5445Meridian Mark RoadSuite 420AtlantaGA 30342USA department of Biology and Center for Cancer Research Tuskegee UniversityCarver Research BuildingTuskegee InstituteAL 36088USA The wallace h.coulter department of biomedical engineering Georgia Institute of Technology313 Ferst Drive AtlantaAtlantaGA 30332USA Samuel-Oschin Comprehensive Cancer Institute Cedars-Sinai Medical Center8750 Beverly Blvd.Atrium 103Los AngelesCA 90048USA Georgia Pediatric Urology 5445 Meridian Mark RdSuite 420AtlantaGA 30342USA Tuskegee University Carver Research Bld.Rm 22TuskegeeAL 36088USA.

To develop and characterize a novel cell culture method for the generation of undifferentiated and differentiated human mesenchymal stem cell 3D structures,we utilized the RWV system with a gelatin-based scaffold.3×10^(6) cells generated homogeneous spheroids and maximum spheroid loading was accomplished after 3 days of *** cultured in undifferentiated spheroids of 3 and 10 days retained expression of CD44,without expression of differentiation *** cultured in adipogenic and osteogenic differentiation media exhibited oil red O staining and von Kossa staining,*** characterization of osteogenic lineage,showed that 10 day spheroids exhibited stronger calcification than any other experimental group corresponding with significant expression of vitamin D receptor,alkaline phosphatase,and *** conclusion this study describes a novel RWV culture method that allowed efficacious engineering of undifferentiated human mesenchymal stem cell spheroids and rapid osteogenic *** use of gelatin scaffolds holds promise to design implantable stem cell tissue of various sizes and shapes for future regenerative treatment.

关键词： Mesenchymal stem cell RWV culture Tissue engineering Differentiation Osteogenesis

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Fully implantable and battery-free wireless optoelectronic system for modulable cancer therapy and real-time monitoring

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npj Flexible Electronics 2023年第1期7卷 119-130页

作者： Kiho Kim In Sik Min Tae hee Kim Do hyeon Kim Seungwon hwang Kyowon Kang Kyubeen Kim Sangun Park Jongmin Lee Young Uk Cho Jung Woo Lee Woon-hong Yeo Young Min Song Youngmee Jung Ki Jun Yu Functional Bio-integrated Electronics and Energy Management Lab School of Electrical and Electronic EngineeringYonsei University50 Yonsei-roSeodaemun-guSeoul 03722Republic of Korea Center for Biomaterials Biomedical Research InstituteKorea Institute of Science and Technology(KIST)Seoul 02792Republic of Korea department of Fusion Research and Collaboration Biomedical Research InstituteSeoul National University HospitalSeoul 03080Republic of Korea School of Electrical engineering and Computer Science(EECS) Gwangju Institute of Science and Technology(GIST)Gwangju 61005Republic of Korea PA1 Foundry BusinessSamsung Electronics1 Samsungjeonja-roHwaseong-siGyeonggi-doRepublic of Korea R&D Center DNA Lab PharmaresearchSeongnam 13486Republic of Korea KU-KIST Graduate School of Converging Science and Technology Korea UniversitySeoul 136-705Republic of Korea School of Materials Science and engineering Energy Materials for Soft Electronics LaboratoryPusan National UniversityBusan 46241Republic of Korea IEN Center for human-Centric Interfaces and engineering and George W.Woodruff School of Mechanical engineering Georgia Institute of TechnologyAtlantaGA 30332USA wallace h.coulter department of biomedical engineering Georgia Institute of Technology and Emory University School of MedicineAtlantaGA 30332USA Institute for Robotics and Intelligent Machines Parker H.Petit Institute for Bioengineering and BiosciencesInstitute for MaterialsNeural Engineering CenterGeorgia Institute of TechnologyAtlantaGA 30332USA School of Electrical and Electronic engineering YU-Korea Institute of Science and Technology(KIST)InstituteYonsei University50Yonsei-roSeodaemun-guSeoul 03722Republic of Korea

Photodynamic therapy(PDT)is attracting attention as a next-generation cancer treatment that can selectively destroy malignant tissues,exhibit fewer side effects,and lack pain during *** PDT systems have recently been developed to resolve the issues of bulky and expensive conventional PDT systems and to implement continuous and repetitive *** implantable PDT systems,however,are not able to perform multiple functions simultaneously,such as modulating light intensity,measuring,and transmitting tumor-related data,resulting in the complexity of cancer ***,we introduce a flexible and fully implantable wireless optoelectronic system capable of continuous and effective cancer treatment by fusing PDT and hyperthermia and enabling tumor size monitoring in *** system exploits micro inorganic light-emitting diodes(μ-LED)that emit light with a wavelength of 624 nm,designed not to affect surrounding normal tissues by utilizing a fully programmable light intensity ofμ-LED and precisely monitoring the tumor size by Si phototransistor during a long-term implantation(2–3 weeks).The superiority of simultaneous cancer treatment and tumor size monitoring capabilities of our system operated by wireless power and data transmissions with a cell phone was confirmed through in vitro experiments,ray-tracing simulation results,and a tumor xenograft mouse model in *** all-in-one single system for cancer treatment offers opportunities to not only enable effective treatment of tumors located deep in the tissue but also enable precise and continuous monitoring of tumor size in real-time.

关键词： optoelectronic enable battery

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System control-mediated drug delivery towards complex systems via nanodiamond carriers

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International Journal of Smart and Nano Materials 2010年第1期1卷 69-81页

作者： Dean ho Chih-Ming ho department of biomedical engineering department of Mechanical engineering Northwestern UniversityEvanstonIL 60208USA Robert h.Lurie Comprehensive Cancer Center Northwestern UniversityChicagoIL 60611USA department of Mechanical and Aerospace engineering University of CaliforniaLos AngelesLACA 90095USA Center for Cell Control A NIH Nanomedicine Development CenterLos AngelesCA 90095USA

Cells represent the basic units of life and contain an intertwined network of signaling and regulatory circuitries that drive the processes of *** processes include the mediation of mechano-sensation,onset of and protection against disease,inflammation,and *** the network of bio-complex systems,each pathway interacts nonlinearly with others through different molecular *** a result,specific functionalities can not be simply linked to the cellular molecules in isolation.A complex system generally possesses very rich information content that can be characterized by the following features:(i)they contain a large number of building blocks;(ii)their interactions among building blocks and with their environment;(iii)they display organization without an external organizing principle being applied;and(iv)they exhibit adaptability and *** properties account for the innate intelligence of biology and its ability to regulate its homeostatic ***,this same complexity underlies,in cancer for example,challenges towards disease management,as the addressing of singular pathways with therapeutic compounds is not ***,combinatorial therapy often serves as a key strategy towards tumor *** iterative searching for optimized therapeutic combinations is indeed a daunting,if not preclusive task,we introduce the feedback system control(FSC)scheme,which may serve as a clinically relevant approach,provided a translational approach towards drug delivery is *** to their innate biocompatibility,which has been comprehensively observed,as well as their ability to delivery virtually any type of therapeutic in a sustained fashion due to their unique surface properties,nanodiamonds may serve as a foundation for nanoenabled combinatorial therapy.

关键词： bio-complex system feedback system control drug delivery,nanodiamond combinatorial medicine signaling network nanomedicine

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多重响应两性离子聚合物的设计、制备和抗菌应用

多重响应两性离子聚合物的设计、制备和抗菌应用

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ASTF2023（第五届）抗菌科学与技术论坛

作者：杨晋涛郑司雨张冬王晓宇王高鹏王懿婷郑洁浙江工业大学材料科学与工程学院 The wallace h.coulter department of biomedical engineering Georgia Institute of Technology and Emory University department of Chemical Biomolecularand Corrosion EngineeringThe University of Akron

两性离子聚合物具有高度的水合能力和优异的生物相容性,被广泛应用于生物防污、药物载体、医学诊断和组织工程材料等领域,现已发展为最具应用前景的生物高分子材料之一。两性离子聚合物的智能化和多功能化将能够进一步拓展其应用领域。... 详细信息

两性离子聚合物具有高度的水合能力和优异的生物相容性,被广泛应用于生物防污、药物载体、医学诊断和组织工程材料等领域,现已发展为最具应用前景的生物高分子材料之一。两性离子聚合物的智能化和多功能化将能够进一步拓展其应用领域。近几年,我们通过对可聚合基团、阴阳离子基团等基元的设计,制备了一系列具有强反"聚电解质效应"盐响应、UCST温度响应及可见光和荧光变色ph响应的两性离子聚合物,利用这些特性,构建了"长效防污-杀菌-释放"的多功能抗菌表面和具有伤口监测-促伤口愈合的功能敷料。本报告将介绍这类两性离子的设计、制备和性能,特别是多重响应特性以及在抗菌、伤口敷料等领域的初步应用探索,期待获得进一步应用启发。

关键词：两性离子聚合物多重响应抗菌表面伤口敷料

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Characterizing Thermal Augmentation of Convection-Enhanced Drug Delivery with the Fiberoptic Microneedle Device

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engineering 2015年第3期1卷 344-350页

作者： R.Lyle hood Rudy T.Andriani Tobias E.Ecker John L.Robertson Christopher G.Rylander department of Nanomedicine Houston Methodist Research Institute department of Mechanical engineering Virginia Tech School of biomedical engineering Virginia Tech department of Mechanical engineering University of Texas

Convection-enhanced delivery （CED） is a promising technique leveraging pressure-driven flow to increase penetration of infused drugs into interstitial spaces. We have developed a fiberoptic microneedle device for inducing local sub-lethal hyperthermia to further improve CED drug distribution volumes, and this study seeks to quantitatively characterize this approach in agarose tissue phantoms. Infusions of dye were conducted in 0.6% （w/w） agarose tissue phantoms with isothermal conditions at 15 ℃, 20℃, 25 ℃, and 30 ℃. Infusion metrics were quantified using a custom shadowgraphy setup and image- processing algorithm. These data were used to build an empirical predictive temporal model of distribution volume as a function of phantom temperature. A second set of proof- of-concept experiments was conducted to evaluate a novel fiberoptic device capable of generating local photothermal heating during fluid infusion. The isothermal infusions showed a positive correlation between temperature and distribution volume, with the volume at 30℃ showing a 7-fold increase at 100 min over the 15 ℃ isothermal case. Infusions during photothermal heating （1064 nm at 500 mW） showed a similar effect with a 3.5-fold increase at 4 h over the control （0 mW）. These results and analyses serve to provide insight into and characterization of heat-mediated enhancement of volumetric dispersal.

关键词： near-infrared laser thermochemotherapy agarose photothermal heating micro-catheter malignant glioma

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