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Immune engineering

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https://www.readbyqxmd.com/read/28647573/focal-adhesion-kinase-signaling-regulates-anti-inflammatory-function-of-bone-marrow-mesenchymal-stromal-cells-induced-by-biomechanical-force
#1
Hyun Jung Lee, Miguel F Diaz, Adesuwa Ewere, Scott D Olson, Charles S Cox, Pamela L Wenzel
Mesenchymal stromal cells (MSCs) have tremendous potential for use in regenerative medicine due to their multipotency and immune cell regulatory functions. Biomimetic physical forces have been shown to direct differentiation and maturation of MSCs in tissue engineering applications; however, the effect of force on immunomodulatory activity of MSCs has been largely overlooked. Here we show in human bone marrow-derived MSCs that wall shear stress (WSS) equivalent to the fluid frictional force present in the adult arterial vasculature significantly enhances expression of four genes that mediate MSC immune regulatory function, PTGS2, HMOX1, IL1RN, and TNFAIP6...
June 21, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28646912/influences-of-age-related-changes-in-mesenchymal-stem-cells-on-macrophages-during-in-vitro-culture
#2
Yuan Yin, Rui-Xin Wu, Xiao-Tao He, Xin-Yue Xu, Jia Wang, Fa-Ming Chen
BACKGROUND: Mesenchymal stem cells (MSCs) have been widely used in cytotherapy and tissue engineering due to their immunosuppressive ability and regenerative potential. Recently, the immunomodulatory influence of MSCs has been gaining increasing attention because their functional roles in modulating immune responses likely have high clinical significance. METHODS: In this study, we investigated the influence of MSCs on macrophages (Mφs) in in-vitro cell culture systems...
June 24, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28646905/mechanistic-understanding-of-nanoparticles-interactions-with-extracellular-matrix-the-cell-and-immune-system
#3
REVIEW
Ayse Basak Engin, Dragana Nikitovic, Monica Neagu, Petra Henrich-Noack, Anca Oana Docea, Mikhail I Shtilman, Kirill Golokhvast, Aristidis M Tsatsakis
Extracellular matrix (ECM) is an extraordinarily complex and unique meshwork composed of structural proteins and glycosaminoglycans. The ECM provides essential physical scaffolding for the cellular constituents, as well as contributes to crucial biochemical signaling. Importantly, ECM is an indispensable part of all biological barriers and substantially modulates the interchange of the nanotechnology products through these barriers. The interactions of the ECM with nanoparticles (NPs) depend on the morphological characteristics of intercellular matrix and on the physical characteristics of the NPs and may be either deleterious or beneficial...
June 24, 2017: Particle and Fibre Toxicology
https://www.readbyqxmd.com/read/28643432/the-penetration-and-phenotype-modulation-of-smooth-muscle-cells-on-surface-heparin-modified-poly-%C3%AE%C2%B5-caprolactone-vascular-scaffold
#4
Jie Cao, Xue Geng, Juan Wen, Qingxuan Li, Lin Ye, Aiying Zhang, Zengguo Feng, Lianrui Guo, Yongquan Gu
The tubular porous poly(ε-caprolactone)(PCL) scaffold was fabricated by electrospinning. After then, the scaffold's surface was firstly eroded by hexyldiamine to endow amine group, and heparin was covalently grafted to the surface to get surface heparin modified scaffold(ShPCL scaffold). It was found that ShPCL scaffold can induce smooth muscle cells (SMCs) to penetrate the scaffold surface, while the SMCs can't penetrate the surface of PCL scaffold. Subsequently, the rabbit SMCs were seeded on the ShPCL scaffold and cultured for 14 days...
June 23, 2017: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/28641531/application-of-alphaviral-vectors-for-immunomodulation-in-cancer-therapy
#5
Anna Zajakina, Karina Spunde, Kenneth Lundstrom
BACKGROUND: The lack of specific and efficient cancer therapies has influenced the development of novel approaches, such as immunotherapy, which from its original application of immunogenic protein delivery has developed into the use of more sophisticated recombinant gene delivery methods to achieve better safety and efficacy profiles. This approach involves viral and non-viral delivery systems. METHODS: Expression vectors have been engineered for alphaviruses, including Semliki Forest virus, Sindbis virus and Venezuelan equine encephalitis virus...
June 21, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28640974/resistance-to-powdery-mildew8-1-boosts-pattern-triggered-immunity-against-multiple-pathogens-in-arabidopsis-and-rice
#6
Yan Li, Yong Zhang, Qing-Xia Wang, Ting-Ting Wang, Xiao-Long Cao, Zhi-Xue Zhao, Sheng-Li Zhao, Yong-Ju Xu, Zhi-Yuan Xiao, Jin-Lu Li, Jing Fan, Hui Yang, Fu Huang, Shunyuan Xiao, Wen-Ming Wang
The Arabidopsis gene RESISTANCE TO POWDERY MILDEW8.1 (RPW8.1) confers resistance to virulent fungal and oomycete pathogens that cause powdery mildew and downy mildew, respectively. However, the underlying mechanism remains unclear. Here, we show that ectopic expression of RPW8.1 boosts pattern-triggered immunity (PTI) resulting in enhanced resistance against different pathogens in both Arabidopsis and rice. In Arabidopsis, transcriptome analysis revealed that ectopic expression of RPW8.1-YFP constitutively up-regulates expression of many pathogen-associated molecular pattern-(PAMP-) inducible genes...
June 22, 2017: Plant Biotechnology Journal
https://www.readbyqxmd.com/read/28637915/tumour-on-a-chip-microfluidic-models-of-tumour-morphology-growth-and-microenvironment
#7
REVIEW
Hsieh-Fu Tsai, Alen Trubelja, Amy Q Shen, Gang Bao
Cancer remains one of the leading causes of death, albeit enormous efforts to cure the disease. To overcome the major challenges in cancer therapy, we need to have a better understanding of the tumour microenvironment (TME), as well as a more effective means to screen anti-cancer drug leads; both can be achieved using advanced technologies, including the emerging tumour-on-a-chip technology. Here, we review the recent development of the tumour-on-a-chip technology, which integrates microfluidics, microfabrication, tissue engineering and biomaterials research, and offers new opportunities for building and applying functional three-dimensional in vitro human tumour models for oncology research, immunotherapy studies and drug screening...
June 2017: Journal of the Royal Society, Interface
https://www.readbyqxmd.com/read/28637876/monocyte-derived-dendritic-cells-with-silenced-pd-1-ligands-and-transpresenting-interleukin-15-stimulate-strong-tumor-reactive-t-cell-expansion
#8
Johan Mj Van den Bergh, Evelien Ljm Smits, Zwi N Berneman, Tim Ja Hutten, Hans De Reu, Viggo Fi Van Tendeloo, Harry Dolstra, Eva Lion, Willemijn Hobo
Although allogeneic stem cell transplantation (allo-SCT) can elicit graft-versus-tumor (GVT) immunity, patients often relapse due to residual tumor cells. As essential orchestrators of the immune system, vaccination with dendritic cells (DCs) is an appealing strategy to boost the GVT-response. Nevertheless, durable clinical responses after DC vaccination are still limited, stressing the need to improve current DC vaccines. Aiming to empower DC potency, we engineered monocyte-derived DCs to deprive them of ligands for the immune checkpoint regulated by programmed death 1 (PD-1)...
June 21, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28634571/current-immunotherapeutic-strategies-to-enhance-oncolytic-virotherapy
#9
REVIEW
Daniel E Meyers, Amanda A Wang, Chandini M Thirukkumaran, Don G Morris
Oncolytic viruses (OV) represent a promising strategy to augment the spectrum of cancer therapeutics. For efficacy, they rely on two general mechanisms: tumor-specific infection/cell-killing, followed by subsequent activation of the host's adaptive immune response. Numerous OV genera have been utilized in clinical trials, ultimately culminating in the 2015 Food and Drug Administration approval of a genetically engineered herpes virus, Talminogene laherparepvec (T-VEC). It is generally accepted that OV as monotherapy have only modest clinical efficacy...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28634472/antifungal-activity-against-filamentous-fungi-of-ts1-a-multifunctional-toxin-from-tityus-serrulatus-scorpion-venom
#10
Welligton M Santussi, Karla C F Bordon, Ana P N Rodrigues Alves, Camila T Cologna, Suraia Said, Eliane C Arantes
Antimicrobial peptides (AMPs) are ubiquitous and multipotent components of the innate immune defense arsenal used by both prokaryotic and eukaryotic organisms. The search for new AMPs has increased in recent years, due to the growing development of microbial resistance to therapeutical drugs. In this work, we evaluate the effects of Tityus serrulatus venom (Tsv), its fractions and its major toxin Ts1, a beta-neurotoxin, on fungi growth. The fractions were obtained by ion-exchange chromatography of Tsv. The growth inhibition of 11 pathogenic and non-pathogenic filamentous fungi (Aspergillus fumigatus, A...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28630926/vasculogenic-hydrogel-enhances-islet-survival-engraftment-and-function-in-leading-extrahepatic-sites
#11
Jessica D Weaver, Devon M Headen, Jahizreal Aquart, Christopher T Johnson, Lonnie D Shea, Haval Shirwan, Andrés J García
Islet transplantation is a promising alternative therapy for insulin-dependent patients, with the potential to eliminate life-threatening hypoglycemic episodes and secondary complications of long-term diabetes. However, widespread application of this therapy has been limited by inadequate graft function and longevity, in part due to the loss of up to 60% of the graft in the hostile intrahepatic transplant site. We report a proteolytically degradable synthetic hydrogel, functionalized with vasculogenic factors for localized delivery, engineered to deliver islet grafts to extrahepatic transplant sites via in situ gelation under physiological conditions...
June 2017: Science Advances
https://www.readbyqxmd.com/read/28630108/inducing-mucosal-iga-a-challenge-for-vaccine-adjuvants-and-delivery-systems
#12
REVIEW
Prosper N Boyaka
Mucosal IgA or secretory IgA (SIgA) are structurally equipped to resist chemical degradation in the harsh environment of mucosal surfaces and enzymes of host or microbial origin. Production of SIgA is finely regulated, and distinct T-independent and T-dependent mechanisms orchestrate Ig α class switching and SIgA responses against commensal and pathogenic microbes. Most infectious pathogens enter the host via mucosal surfaces. To provide a first line of protection at these entry ports, vaccines are being developed to induce pathogen-specific SIgA in addition to systemic immunity achieved by injected vaccines...
July 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28628616/therapeutic-administration-of-a-recombinant-human-monoclonal-antibody-reduces-the-severity-of-chikungunya-virus-disease-in-rhesus-macaques
#13
Rebecca Broeckel, Julie M Fox, Nicole Haese, Craig N Kreklywich, Soila Sukulpovi-Petty, Alfred Legasse, Patricia P Smith, Michael Denton, Carsten Corvey, Shiv Krishnan, Lois M A Colgin, Rebecca M Ducore, Anne D Lewis, Michael K Axthelm, Marie Mandron, Pierre Cortez, Jonathan Rothblatt, Ercole Rao, Ingo Focken, Kara Carter, Gopal Sapparapau, James E Crowe, Michael S Diamond, Daniel N Streblow
Chikungunya virus (CHIKV) is a mosquito-borne virus that causes a febrile syndrome in humans associated with acute and chronic debilitating joint and muscle pain. Currently no licensed vaccines or therapeutics are available to prevent or treat CHIKV infections. We recently isolated a panel of potently neutralizing human monoclonal antibodies (mAbs), one (4N12) of which exhibited prophylactic and post-exposure therapeutic activity against CHIKV in immunocompromised mice. Here, we describe the development of an engineered CHIKV mAb, designated SVIR001, that has similar antigen binding and neutralization profiles to its parent, 4N12...
June 19, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28627778/engineering-cho-cells-with-an-oncogenic-kit-improves-cells-growth-resilience-to-stress-and-productivity
#14
Mohamed Mahameed, Boaz Tirosh
An optimized biomanufacturing process in mammalian cells is contingent on the ability of the producing cells to reach high viable cell densities. In addition, at the peak of growth, cells need to continue producing the biological entity at a consistent quality. Thus, engineering cells with robust growth performance and resilience to variable stress conditions is highly desirable. The tyrosine kinase receptor, KIT, plays a key role in cell differentiation and the survival of several immune cell types. Its oncogenic mutant, D816V, endows cells with high proliferation capacity and resistance to kinase inhibitors...
June 19, 2017: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/28626230/engineering-of-obligate-intracellular-bacteria-progress-challenges-and-paradigms
#15
REVIEW
Erin E McClure, Adela S Oliva Chávez, Dana K Shaw, Jason A Carlyon, Roman R Ganta, Susan M Noh, David O Wood, Patrik M Bavoil, Kelly A Brayton, Juan J Martinez, Jere W McBride, Raphael H Valdivia, Ulrike G Munderloh, Joao H F Pedra
It is estimated that approximately one billion people are at risk of infection with obligate intracellular bacteria, but little is known about the underlying mechanisms that govern their life cycles. The difficulty in studying Chlamydia spp., Coxiella spp., Rickettsia spp., Anaplasma spp., Ehrlichia spp. and Orientia spp. is, in part, due to their genetic intractability. Recently, genetic tools have been developed; however, optimizing the genomic manipulation of obligate intracellular bacteria remains challenging...
June 19, 2017: Nature Reviews. Microbiology
https://www.readbyqxmd.com/read/28625831/engineering-challenges-for-brain-tumor-immunotherapy
#16
Johnathan G Lyon, Nassir Mokarram, Tarun Saxena, Sheridan L Carroll, Ravi V Bellamkonda
Malignant brain tumors represent one of the most devastating forms of cancer with abject survival rates that have not changed in the past 60years. This is partly because the brain is a critical organ, and poses unique anatomical, physiological, and immunological barriers. The unique interplay of these barriers also provides an opportunity for creative engineering solutions. Cancer immunotherapy, a means of harnessing the host immune system for anti-tumor efficacy, is becoming a standard approach for treating many cancers...
June 15, 2017: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/28625827/cells-as-advanced-therapeutics-state-of-the-art-challenges-and-opportunities-in-large-scale-biomanufacturing-of-high-quality-cells-for-adoptive-immunotherapies
#17
Nate J Dwarshuis, Kirsten Parratt, Adriana Santiago-Miranda, Krishnendu Roy
Therapeutic cells hold tremendous promise in treating currently incurable, chronic diseases since they perform multiple, integrated, complex functions in vivo compared to traditional small-molecule drugs or biologics. However, they also pose significant challenges as therapeutic products because (a) their complex mechanisms of actions are difficult to understand and (b) low-cost bioprocesses for large-scale, reproducible manufacturing of cells have yet to be developed. Immunotherapies using T cells and dendritic cells (DCs) have already shown great promise in treating several types of cancers, and human mesenchymal stromal cells (hMSCs) are now extensively being evaluated in clinical trials as immune-modulatory cells...
June 15, 2017: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/28625015/crispr-cas9-mediated-lag-3-disruption-in-car-t-cells
#18
Yongping Zhang, Xingying Zhang, Chen Cheng, Wei Mu, Xiaojuan Liu, Na Li, Xiaofei Wei, Xiang Liu, Changqing Xia, Haoyi Wang
T cells engineered with chimeric antigen receptor (CAR) have been successfully applied to treat advanced refractory B cell malignancy. However, many challenges remain in extending its application toward the treatment of solid tumors. The immunosuppressive nature of tumor microenvironment is considered one of the key factors limiting CAR-T efficacy. One negative regulator of Tcell activity is lymphocyte activation gene-3 (LAG-3). We successfully generated LAG-3 knockout Tand CAR-T cells with high efficiency using CRISPR-Cas9 mediated gene editing and found that the viability and immune phenotype were not dramatically changed during in vitro culture...
June 17, 2017: Frontiers of Medicine
https://www.readbyqxmd.com/read/28624670/towards-engineering-of-hormonal-crosstalk-in-plant-immunity
#19
REVIEW
Alexandra M Shigenaga, Matthias L Berens, Kenichi Tsuda, Cristiana T Argueso
Plant hormones regulate physiological responses in plants, including responses to pathogens and beneficial microbes. The last decades have provided a vast amount of evidence about the contribution of different plant hormones to plant immunity, and also of how they cooperate to orchestrate immunity activation, in a process known as hormone crosstalk. In this review we highlight the complexity of hormonal crosstalk in immunity and approaches currently being used to further understand this process, as well as perspectives to engineer hormone crosstalk for enhanced pathogen resistance and overall plant fitness...
June 15, 2017: Current Opinion in Plant Biology
https://www.readbyqxmd.com/read/28624655/biological-responses-to-m13-bacteriophage-modified-titanium-surfaces-in-vitro
#20
Yuhua Sun, Yiting Li, Baohua Wu, Jianxin Wang, Xiong Lu, Shuxin Qu, Jie Weng, Bo Feng
Phage-based materials have showed great potential in tissue engineering application. However, it is unknown what inflammation response will happen to this kind of materials. This work is to explore the biological responses to M13 bacteriophage (phage) modified titanium surfaces in vitro from the aspects of their interaction with macrophages, osteoblasts and mineralization behavior. Pretreated Ti surface, Ti surfaces with noncrosslinked phage film (APP) and crosslinked phage film (APPG) were compared. Phage films could limit the macrophage adhesion and activity due to inducing adherent-cell apoptosis...
June 14, 2017: Acta Biomaterialia
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