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Nature Biomedical Engineering

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https://www.readbyqxmd.com/read/30271673/effects-of-3d-culturing-conditions-on-the-transcriptomic-profile-of-stem-cell-derived-neurons
#1
Halil Tekin, Sean Simmons, Beryl Cummings, Linyi Gao, Xian Adiconis, Cynthia C Hession, Ayan Ghoshal, Danielle Dionne, Sourav R Choudhury, Volkan Yesilyurt, Neville E Sanjana, Xi Shi, Congyi Lu, Matthias Heidenreich, Jen Q Pan, Joshua Z Levin, Feng Zhang
Understanding neurological diseases requires tractable genetic systems. Engineered 3D neural tissues are an attractive choice, but how the cellular transcriptomic profiles in these tissues are affected by the encapsulating materials and are related to the human-brain transcriptome is not well understood. Here, we report the characterization of the effects of culturing conditions on the transcriptomic profiles of induced neuronal cells, as well as a method for the rapid generation of 3D co-cultures of neuronal and astrocytic cells from the same pool of human embryonic stem cells...
July 2018: Nature Biomedical Engineering
https://www.readbyqxmd.com/read/30263872/first-in-human-study-of-the-safety-and-viability-of-intraocular-robotic-surgery
#2
T L Edwards, K Xue, H C M Meenink, M J Beelen, G J L Naus, M P Simunovic, M Latasiewicz, A D Farmery, M D de Smet, R E MacLaren
Microsurgery of the retina would be dramatically improved by instruments that offer supra-human precision. Here, we report the results of a first-in-human study of remotely controlled robot-assisted retinal surgery performed through a telemanipulation device. Specifically, 12 patients requiring dissection of the epiretinal or inner limiting membrane over the macula were randomly assigned to either undergo robot-assisted-surgery or manual surgery, under general anaesthesia. We evaluated surgical success, duration of surgery and amount of retinal microtrauma as a proxy for safety...
June 18, 2018: Nature Biomedical Engineering
https://www.readbyqxmd.com/read/30151330/mechanically-induced-development-and-maturation-of-human-intestinal-organoids-in-vivo
#3
Holly M Poling, David Wu, Nicole Brown, Michael Baker, Taylor A Hausfeld, Nhan Huynh, Samuel Chaffron, James C Y Dunn, Simon P Hogan, James M Wells, Michael A Helmrath, Maxime M Mahe
The natural ability of stem cells to self-organize into functional tissue has been harnessed for the production of functional human intestinal organoids. Although dynamic mechanical forces play a central role in intestinal development and morphogenesis, conventional methods for the generation of intestinal organoids have relied solely on biological factors. Here, we show that the incorporation of uniaxial strain, by using compressed nitinol springs, in human intestinal organoids transplanted into the mesentery of mice induces growth and maturation of the organoids...
June 2018: Nature Biomedical Engineering
https://www.readbyqxmd.com/read/30116654/towards-superior-dendritic-cell-vaccines-for-cancer-therapy
#4
Mansi Saxena, Sreekumar Balan, Vladimir Roudko, Nina Bhardwaj
No abstract text is available yet for this article.
June 2018: Nature Biomedical Engineering
https://www.readbyqxmd.com/read/30271672/cardiac-recovery-via-extended-cell-free-delivery-of-extracellular-vesicles-secreted-by-cardiomyocytes-derived-from-induced-pluripotent-stem-cells
#5
Bohao Liu, Benjamin W Lee, Koki Nakanishi, Aranzazu Villasante, Rebecca Williamson, Jordan Metz, Jinho Kim, Mariko Kanai, Lynn Bi, Kristy Brown, Gilbert Di Paolo, Shunichi Homma, Peter A Sims, Veli K Topkara, Gordana Vunjak-Novakovic
The ability of extracellular vesicles (EVs) to regulate a broad range of cellular processes has recently been exploited for the treatment of diseases. For example, EVs secreted by stem cells injected into infarcted hearts can induce recovery through the delivery of stem-cell-specific miRNAs. However, the retention of the EVs and the therapeutic effects are short-lived. Here, we show that an engineered hydrogel patch capable of slowly releasing EVs secreted from cardiomyocytes derived from induced pluripotent stem (iPS) cells reduced arrhythmic burden, promoted ejection-fraction recovery, decreased cardiomyocyte apoptosis 24 hours after infarction, and reduced infarct size and cell hypertrophy 4 weeks post-infarction when implanted onto infarcted rat hearts...
May 2018: Nature biomedical engineering
https://www.readbyqxmd.com/read/30283724/diagnosis-of-sepsis-from-a-drop-of-blood-by-measurement-of-spontaneous-neutrophil-motility-in-a-microfluidic-assay
#6
Felix Ellett, Julianne Jorgensen, Anika L Marand, Yuk M Liu, Myriam M Martinez, Vicki Sein, Kathryn L Butler, Jarone Lee, Daniel Irimia
Current methods for the diagnosis of sepsis have insufficient precision, causing regular misdiagnoses. Microbiological tests can help diagnose sepsis but are usually too slow to have an impact on timely clinical-decision making. Neutrophils have high sensitivity to infections, yet measurements of neutrophil surface markers, genomic changes, and phenotype alterations have had only a marginal effect on sepsis diagnosis. Here, we report a microfluidic assay that measures the spontaneous motility of neutrophils in the context of plasma, in one droplet of blood...
April 2018: Nature Biomedical Engineering
https://www.readbyqxmd.com/read/30237910/magnetic-resonance-multitasking-for-motion-resolved-quantitative-cardiovascular-imaging
#7
Anthony G Christodoulou, Jaime L Shaw, Christopher Nguyen, Qi Yang, Yibin Xie, Nan Wang, Debiao Li
Quantitative cardiovascular magnetic resonance (CMR) imaging can be used to characterize fibrosis, oedema, ischaemia, inflammation and other disease conditions. However, the need to reduce artefacts arising from body motion through a combination of electrocardiography (ECG) control, respiration control, and contrast-weighting selection makes CMR exams lengthy. Here, we show that physiological motions and other dynamic processes can be conceptualized as multiple time dimensions that can be resolved via low-rank tensor imaging, allowing for motion-resolved quantitative imaging with up to four time dimensions...
April 2018: Nature Biomedical Engineering
https://www.readbyqxmd.com/read/29963329/cell-type-specific-brain-methylomes-profiled-via-ultralow-input-microfluidics
#8
Sai Ma, Mario de la Fuente Revenga, Zhixiong Sun, Chen Sun, Travis W Murphy, Hehuang Xie, Javier González-Maeso, Chang Lu
Methylomic analyses typically require substantial amounts of DNA, thus hindering studies involving scarce samples. Here, we show that microfluidic diffusion-based reduced representative bisulfite sequencing (MID-RRBS) permits high-quality methylomic profiling with nanogram-to-single-cell quantities of starting DNA. We used the microfluidic device, which allows for efficient bisulfite conversion with high DNA recovery, to analyse genome-wide DNA methylation in cell nuclei isolated from mouse brains and sorted into NeuN+ (primarily neuronal) and NeuN- (primarily glial) fractions, and to establish cell-type-specific methylomes...
March 2018: Nature Biomedical Engineering
https://www.readbyqxmd.com/read/29955439/antibiotic-loaded-nanoparticles-targeted-to-the-site-of-infection-enhance-antibacterial-efficacy
#9
Sazid Hussain, Jinmyoung Joo, Jinyoung Kang, Byungji Kim, Gary B Braun, Zhi-Gang She, Dokyoung Kim, Aman P Mann, Tarmo Mölder, Tambet Teesalu, Santina Carnazza, Salvatore Guglielmino, Michael J Sailor, Erkki Ruoslahti
Bacterial resistance to antibiotics has made it necessary to resort to antibiotics that have considerable toxicities. Here, we show that the cyclic 9-amino acid peptide CARGGLKSC (CARG), identified via phage display on Staphylococcus aureus ( S. aureus ) bacteria and through in vivo screening in mice with S. aureus -induced lung infections, increases the antibacterial activity of CARG-conjugated vancomycin-loaded nanoparticles in S. aureus -infected tissues and reduces the needed overall systemic dose, minimizing side effects...
February 2018: Nature Biomedical Engineering
https://www.readbyqxmd.com/read/29721363/prolonged-survival-of-transplanted-stem-cells-after-ischaemic-injury-via-the-slow-release-of-pro-survival-peptides-from-a-collagen-matrix
#10
Andrew S Lee, Mohammed Inayathullah, Maarten A Lijkwan, Xin Zhao, Wenchao Sun, Sujin Park, Wan Xing Hong, Mansi B Parekh, Andrey V Malkovskiy, Edward Lau, Xulei Qin, Venkata Raveendra Pothineni, Verónica Sanchez-Freire, Wendy Y Zhang, Nigel G Kooreman, Antje D Ebert, Charles K F Chan, Patricia K Nguyen, Jayakumar Rajadas, Joseph C Wu
Stem-cell-based therapies hold considerable promise for regenerative medicine. However, acute donor-cell death within several weeks after cell delivery remains a critical hurdle for clinical translation. Co-transplantation of stem cells with pro-survival factors can improve cell engraftment, but this strategy has been hampered by the typically short half-lives of the factors and by the use of Matrigel and other scaffolds that are not chemically defined. Here, we report a collagen-dendrimer biomaterial crosslinked with pro-survival peptide analogues that adheres to the extracellular matrix and slowly releases the peptides, significantly prolonging stem cell survival in mouse models of ischaemic injury...
February 2018: Nature Biomedical Engineering
https://www.readbyqxmd.com/read/30345161/tlr7-8-agonist-loaded-nanoparticles-promote-the-polarization-of-tumour-associated-macrophages-to-enhance-cancer-immunotherapy
#11
Christopher B Rodell, Sean P Arlauckas, Michael F Cuccarese, Christopher S Garris, Ran Li, Maaz S Ahmed, Rainer H Kohler, Mikael J Pittet, Ralph Weissleder
Tumour-associated macrophages (TAMs) are abundant in many cancers, and often display an immune-suppressive M2-like phenotype that fosters tumour growth and promotes resistance to therapy. Yet macrophages are highly plastic and can also acquire an anti-tumourigenic M1-like phenotype. Here, we show that R848, an agonist of the toll-like receptors (TLRs) TLR7 and TLR8 identified in a morphometric-based screen, is a potent driver of the M1 phenotype in vitro and that R848-loaded β-cyclodextrin nanoparticles (CDNPs) lead to efficient drug delivery to TAMs in vivo...
2018: Nature Biomedical Engineering
https://www.readbyqxmd.com/read/30288339/organ-specific-metastases-obtained-by-culturing-colorectal-cancer-cells-on-tissue-specific-decellularized-scaffolds
#12
Xi Tian, Michael E Werner, Kyle C Roche, Ariel D Hanson, Henry P Foote, Stephanie K Yu, Samuel B Warner, Jonathan A Copp, Haydee Lara, Eliane L Wauthier, Joseph M Caster, Laura E Herring, Longzhen Zhang, Joel E Tepper, David S Hsu, Tian Zhang, Lola M Reid, Andrew Z Wang
Metastatic disease remains the primary cause of mortality in cancer patients. Yet the number of available in vitro models to study metastasis is limited by challenges in the recapitulation of the metastatic microenvironment in vitro , and by difficulties in maintaining colonized-tissue specificity in the expansion and maintenance of metastatic cells. Here, we show that decellularized scaffolds that retain tissue-specific extracellular-matrix (ECM) components and bound signaling molecules enable, when seeded with colorectal cancer (CRC) cells, the spontaneous formation of three-dimensional cell colonies that histologically, molecularly and phenotypically resemble in vivo metastases...
2018: Nature Biomedical Engineering
https://www.readbyqxmd.com/read/30221032/a-ribonucleoprotein-octamer-for-targeted-sirna-delivery
#13
Wanyi Tai, Junwei Li, Eva Corey, Xiaohu Gao
Hurdles in cell-specific delivery of small interfering RNA (siRNA) in vivo hinder the clinical translation of RNA interference (RNAi). A fundamental problem concerns conflicting requirements for the design of the delivery vehicles: cationic materials facilitate cargo condensation and endosomolysis, yet hinder in vivo targeting and colloidal stability. Here, we describe a self-assembled, compact (~30 nm) and biocompatible ribonucleoprotein-octamer nanoparticle that achieves endosomal destabilization and targeted delivery...
2018: Nature Biomedical Engineering
https://www.readbyqxmd.com/read/29998038/prediction-of-off-target-activities-for-the-end-to-end-design-of-crispr-guide-rnas
#14
Jennifer Listgarten, Michael Weinstein, Benjamin P Kleinstiver, Alexander A Sousa, J Keith Joung, Jake Crawford, Kevin Gao, Luong Hoang, Melih Elibol, John G Doench, Nicolo Fusi
The CRISPR-Cas9 system provides unprecedented genome editing capabilities. However, off-target effects lead to sub-optimal usage and additionally are a bottleneck in the development of therapeutic uses. Herein, we introduce the first machine learning-based approach to off-target prediction, yielding a state-of-the-art model for CRISPR-Cas9 that outperforms all other guide design services. Our approach, Elevation, consists of two interdependent machine learning models-one for scoring individual guide-target pairs, and another which aggregates these guide-target scores into a single, overall summary guide score...
January 2018: Nature Biomedical Engineering
https://www.readbyqxmd.com/read/29862136/targeted-repair-of-heart-injury-by-stem-cells-fused-with-platelet-nanovesicles
#15
Junnan Tang, Teng Su, Ke Huang, Phuong-Uyen Dinh, Zegen Wang, Adam Vandergriff, Michael T Hensley, Jhon Cores, Tyler Allen, Taosheng Li, Erin Sproul, Emily Mihalko, Leonard J Lobo, Laura Ruterbories, Alex Lynch, Ashley Brown, Thomas G Caranasos, Deliang Shen, George A Stouffer, Zhen Gu, Jinying Zhang, Ke Cheng
Stem cell transplantation, as used clinically, suffers from low retention and engraftment of the transplanted cells. Inspired by the ability of platelets to recruit stem cells to sites of injury on blood vessels, we hypothesized that platelets might enhance the vascular delivery of cardiac stem cells (CSCs) to sites of myocardial infarction injury. Here, we show that CSCs with platelet nanovesicles fused onto their surface membranes express platelet surface markers that are associated with platelet adhesion to injury sites...
2018: Nature Biomedical Engineering
https://www.readbyqxmd.com/read/30147994/nanoparticles-for-crispr-cas9-delivery
#16
Zachary Glass, Yamin Li, Qiaobing Xu
The DNA mutation that causes Duchenne muscular dystrophy in mice can be corrected, with minimal off-target effects, by gold nanoparticles carrying the CRISPR components.
November 2017: Nature Biomedical Engineering
https://www.readbyqxmd.com/read/29456878/non-destructive-two-photon-excited-fluorescence-imaging-identifies-early-nodules-in-calcific-aortic-valve-disease
#17
Lauren M Baugh, Zhiyi Liu, Kyle P Quinn, Sam Osseiran, Conor L Evans, Gordon S Huggins, Philip W Hinds, Lauren D Black, Irene Georgakoudi
Calcifications occur during the development of healthy bone, and at the onset of calcific aortic-valve disease (CAVD) and many other pathologies. Although the mechanisms regulating early calcium deposition are not fully understood, they may provide targets for new treatments and for early interventions. Here, we show that two-photon excited fluorescence (TPEF) can provide quantitative and sensitive readouts of calcific nodule formation, in particular in the context of CAVD. Specifically, by means of the decomposition of TPEF spectral images from excised human CAVD valves and from rat bone prior to and following demineralization, as well as from calcific nodules formed within engineered gels, we identified an endogenous fluorophore that correlates with the level of mineralization in the samples...
November 2017: Nature biomedical engineering
https://www.readbyqxmd.com/read/29450107/macrogenomic-engineering-via-modulation-of-the-scaling-of-chromatin-packing-density
#18
Luay M Almassalha, Greta M Bauer, Wenli Wu, Lusik Cherkezyan, Di Zhang, Alexis Kendra, Scott Gladstein, John E Chandler, David VanDerway, Brandon-Luke L Seagle, Andrey Ugolkov, Daniel D Billadeau, Thomas V O'Halloran, Andrew P Mazar, Hemant K Roy, Igal Szleifer, Shohreh Shahabi, Vadim Backman
Many human diseases result from the dysregulation of the complex interactions between tens to thousands of genes. However, approaches for the transcriptional modulation of many genes simultaneously in a predictive manner are lacking. Here, through the combination of simulations, systems modelling and in vitro experiments, we provide a physical regulatory framework based on chromatin packing-density heterogeneity for modulating the genomic information space. Because transcriptional interactions are essentially chemical reactions, they depend largely on the local physical nanoenvironment...
November 2017: Nature Biomedical Engineering
https://www.readbyqxmd.com/read/30263871/transcriptomic-and-epigenomic-differences-in-human-induced-pluripotent-stem-cells-generated-from-six-reprogramming-methods
#19
Jared M Churko, Jaecheol Lee, Mohamed Ameen, Mingxia Gu, Meenakshi Venkatasubramanian, Sebastian Diecke, Karim Sallam, Hogune Im, Gavin Wang, Joseph D Gold, Nathan Salomonis, Michael P Snyder, Joseph C Wu
Many reprogramming methods can generate human induced pluripotent stem cells (hiPSCs) that closely resemble human embryonic stem cells (hESCs). This has led to assessments of how similar hiPSCs are to hESCs, by evaluating differences in gene expression, epigenetic marks and differentiation potential. However, all previous studies were performed using hiPSCs acquired from different laboratories, passage numbers, culturing conditions, genetic backgrounds and reprogramming methods, all of which may contribute to the reported differences...
October 2017: Nature Biomedical Engineering
https://www.readbyqxmd.com/read/29750130/light-sheet-microscopy-for-slide-free-non-destructive-pathology-of-large-clinical-specimens
#20
Adam K Glaser, Nicholas P Reder, Ye Chen, Erin F McCarty, Chengbo Yin, Linpeng Wei, Yu Wang, Lawrence D True, Jonathan T C Liu
For the 1.7 million patients per year in the U.S. who receive a new cancer diagnosis, treatment decisions are largely made after a histopathology exam. Unfortunately, the gold standard of slide-based microscopic pathology suffers from high inter-observer variability and limited prognostic value due to sampling limitations and the inability to visualize tissue structures and molecular targets in their native 3D context. Here, we show that an open-top light-sheet microscope optimized for non-destructive slide-free pathology of clinical specimens enables the rapid imaging of intact tissues at high resolution over large 2D and 3D fields of view, with the same level of detail as traditional pathology...
July 2017: Nature Biomedical Engineering
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