وأيد العمل من المنح 1K25MH089851 ، 1P01DA028555 - 01A1 ، NS034239 2R01 ، 2R37 NS36126 ، P01 NS31492 ، P20RR 15635 ، P01MH64570 وNS43985 P01 من المعاهد الوطنية للصحة. الكتاب أشكر السيدة روبن تايلور لقراءة نقدية للمخطوطة وغير المسددة دعم رسم والأدبية. فإن الكتاب بالشكر أيضا إلى ايرين ماكنتاير ، ميلون ميليسا ، ورايس ليندسي لدعمها التقني.

<ol>
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الإعلان عن أي تضارب في المصالح.

التسجيل الدقيق لنتائج التصوير مع الأنسجة داخل الجسم الحي هو خطوة حاسمة في تطوير المؤشرات الحيوية للكشف عن التصوير ، وتحديد مراحل المرض العصبي. بعض القياسات التصوير من المحتمل أن تكون مرتبطة مع التغيرات المورفولوجية الإجمالي بما في ذلك التغيرات في خصائص الاسترخاء المغناطيسي للأنسجة المستخدمة للكشف عن وجود مرض السرطان والمادة البيضاء. طرق أخرى أكثر دقة ، مثل زارة التجارة والصناعة ، من المرجح أن كشف التغيرات الخلوية المبكرة التي قد لا تكون قابلة للكشف عن التغيرات النسيجية التي يسببها هذا المرض لا تظهر إلا في وقت لاحق من مراحل المرض. علامات أخرى قد زال ، مثل علامات الطيفية ، يمكن للتغيرات مؤشرات مبكرة وقابلة للانتكاس ، والتي تسبق حتى الألطف التعديلات الخلوية. ويمكن تحديد Biodistribution غير جراحية باستخدام مجموعة متنوعة من الطرق. الأولية غير الغازية الأساليب التخطيط الطبقي لانبعاثات الالكترونات الايجابية (PET) ، واحدة الفوتون التصوير المقطعي (SPECT) ، والتصوير الضوئي ، والتصوير بالرنين المغناطيسي. وقد استخدمت في الطب النووي والتصوير مقرها (PET وSPECT) على مر السنين لbiodistribution كثيرة ، ولكن تقتصر هذه الأساليب من حياة نصف radiotracers المستخدمة لوصفها أو المركبات النانوية ، وخاصة لاستشفاف PET. ويمكن استخدام التصوير الضوئي للقوارض صغيرة ولكن لا يمكن ترجمته إلى استخدام البشري باستثناء مناطق يسهل الوصول إليها ، مثل الأورام السطحية بسبب امتصاص الضوء وتشتت الضوء. بالإضافة إلى ذلك ، فإنه من الصعب قياس الاشارات الضوئية لهذه الأسباب نفسها. التصوير بالرنين المغناطيسي يستخدم العلامات الثابتة مثل سبيو التي يمكن تتبعها في الجسم خلال فترة أسابيع. هذا ، أيضا ، لا بد من استخدامها بحذر ، كما يمكن نقل التسمية إلى خلايا مختلفة أو أن يكون استيعابها من قبل الهيئة. ويمكن توفير نوعية الكشف عن سبيو في التصوير بالرنين المغناطيسي من قبل مجموعة متنوعة من الطرق. وتستخدم طرق الكشف ، والتي توفر اشارات ايجابية وكذلك سلبية ، لتحسين النوعية من التصوير بالرنين المغناطيسي للكشف عن وجود سبيو في الأنسجة. وقد استخدم أسلوب الطرح المستخدمة في هذا العمل من قبل الآخرين ، وكذلك 28. وتشمل المناهج الأخرى قبالة الكشف بالرنين 29-31 ، مرحلة التصوير الحساسة التي تنتج نمطا سيما بالقرب من فراغات سبيو 32 ، وصورة الصفر الوقت الذي يستخدم الصدى الترجيح T1 لإنتاج كثافة إشارة إيجابية في منطقة سبيو 33. النهوض من هذه الطرق لتحسين الكميات التسمية ، وحساسية وخصوصية هي منطقة نشطة للبحث اليوم.

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		<th>Material Name</th>
		<th>Type</th>
		<th>Company</th>
		<th>Catalogue Number</th>
		<th>Comment</th>
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<td>Isoflurane</td>
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<td>Medical Oxygen</td>
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<td>Isoflurane vaporizer</td>
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<td>Rodent gas anesthesia mask</td>
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<td>MRI compatible Stereotactic head holder</td>
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<td>Syringe</td>
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<td>Polyethylene catheter tubing</td>
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<td>Non-magnetic needle</td>
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<td>Eye lubricant</td>
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<td>Gauze</td>
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<td>Tape</td>
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<td>Perfusion media</td>
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<td>OCT compound for embedding tissue</td>
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<td>MRI system</td>
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<td>Digital Camera</td>
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<td>Tissue Sectioning Cryostat</td>
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registered bioimaging of nanomaterials for diagnostic and therapeutic monitoring

يمكن أن يتم من خلال تنقلها Nanomedications الدم الضامة - الوحيدات في نظام شبكي (RES ؛ الطحال والكبد الغدد الليمفاوية ،) ووضع حد للأجهزة. وتشمل هذه الرئة ، RES ، والدماغ والمنطوق خلال نوع فيروس نقص المناعة البشرية واحدة (HIV - 1) العدوى. دخول البلاعم في الأنسجة غير الملحوظة في مجالات تكرار HIV - 1 والمواقع النشطة من الالتهابات. من أجل تقييم إمكانات والضامة ، nanocarriers superparamagnetic أكسيد الحديد و / أو الجزيئات المحملة المخدرات المغلفة مع السطحي حقنت في الفئران حقنا HIV - 1 بالتهاب الدماغ. هذا وقد تم إجراء تقييم كمي والجسيمات biodistribution المخدرات. والتحقق من صحة نتائج التصوير بالرنين المغناطيسي فحص (MRI) من قبل coregistration النسيجية وتعزيز معالجة الصور. وجرى تقييم نهاية الجهاز المرض الذي تمثله الأنسجة الدماغية تعديلها من قبل التصوير بالرنين المغناطيسي. مظاهرة للهجرة قوية من nanoformulations إلى مناطق الدماغ الاتصال يوفر &quot;دليل على مفهوم&quot; لاستخدام تقنيات متقدمة لمراقبة الهجرة bioimaging البلاعم. الأهم ، وانحرافات في الأنسجة في الدماغ ترتبط bioimaging المعلمات جعل المرافق العامة للدراسات التصوير بالرنين المغناطيسي في التوزيع الخلية في مرض ممكنا. نحن يفترض أن استخدام مثل هذه الأساليب يمكن أن تقدم مؤشر في الوقت الحقيقي من عبء المرض والفعالية العلاجية المحتملة مع متعدية إلى البشر.

Watch this Scientific Journal Video about Registered Bioimaging of Nanomaterials for Diagnostic and Therapeutic Monitoring at JoVE.com

Registered Bioimaging of Nanomaterials for Diagnostic and Therapeutic Monitoring

الأساليب المستخدمة لتقييم Bioimaging biodistribution خلية من جزيئات قابلة للتطبيق لرصد العلاجية والتشخيصية للمركبات nanoformulated. الأساليب المذكورة هنا هي حساسة ومحددة عندما المقررة coregistration النسيجية. المنهجيات توفير مسارا متعدية من القوارض إلى تطبيقات الإنسان.

Bioimaging مسجلة لرصد المواد النانوية للتشخيص والعلاج

Nanomedications can be carried by blood borne monocyte-macrophages into the reticuloendothelial system (RES; spleen, liver, lymph nodes) and to end ...

registered-bioimaging-nanomaterials-for-diagnostic-therapeutic

Research

JoVE Journal

Bioengineering

10.3K Views.  University of Nebraska Medical Center. الأساليب المستخدمة لتقييم Bioimaging biodistribution خلية من جزيئات قابلة للتطبيق لرصد العلاجية والتشخيصية للمركبات nanoformulated. الأساليب المذكورة هنا هي حساسة ومحددة عندما المقررة coregistration النسيجية. المنهجيات توفير مسارا متعدية من القوارض إلى تطبيقات الإنسان.

Video: Registered Bioimaging of Nanomaterials for Diagnostic and Therapeutic Monitoring

Low Molecular Weight Protein Enrichment on Mesoporous Silica Thin Films for Biomarker Discovery

The identification of circulating biomarkers holds great potential for non invasive approaches in early diagnosis and prognosis, as well as for the monitoring of therapeutic efficiency.1-3 The circulating low molecular weight proteome (LMWP) composed of small proteins shed from tissues and cells or peptide fragments derived from the proteolytic degradation of larger proteins, has been associated with the pathological condition in patients and likely reflects the state of disease.4,5 Despite these potential clinical applications, the use of Mass Spectrometry (MS) to profile the LMWP from biological fluids has proven to be very challenging due to the large dynamic range of protein and peptide concentrations in serum.6 Without sample pre-treatment, some of the more highly abundant proteins obscure the detection of low-abundance species in serum/plasma. Current proteomic-based approaches, such as two-dimensional polyacrylamide gel-electrophoresis (2D-PAGE) and shotgun proteomics methods are labor-intensive, low throughput and offer limited suitability for clinical applications.7-9 Therefore, a more effective strategy is needed to isolate LMWP from blood and allow the high throughput screening of clinical samples. 
Here, we present a fast, efficient and reliable multi-fractionation system based on mesoporous silica chips to specifically target and enrich LMWP.10,11 Mesoporous silica (MPS) thin films with tunable features at the nanoscale were fabricated using the triblock copolymer template pathway. Using different polymer templates and polymer concentrations in the precursor solution, various pore size distributions, pore structures, connectivity and surface properties were determined and applied for selective recovery of low mass proteins. The selective parsing of the enriched peptides into different subclasses according to their physicochemical properties will enhance the efficiency of recovery and detection of low abundance species. In combination with mass spectrometry and statistic analysis, we demonstrated the correlation between the nanophase characteristics of the mesoporous silica thin films and the specificity and efficacy of low mass proteome harvesting. The results presented herein reveal the potential of the nanotechnology-based technology to provide a powerful alternative to conventional methods for LMWP harvesting from complex biological fluids. Because of the ability to tune the material properties, the capability for low-cost production, the simplicity and rapidity of sample collection, and the greatly reduced sample requirements for analysis, this novel nanotechnology will substantially impact the field of proteomic biomarker research and clinical proteomic assessment.

We developed a technology based on mesoporous silica thin film for the selective recovery of low molecular weight proteins and peptides from human serum. The physico-chemical properties of our mesoporous chips were finely tuned to provide substantial control in peptide enrichment and consequently profile the serum proteome for diagnostic purposes.

بروتين منخفض الوزن الجزيئي تخصيب اليورانيوم على أفلام السيليكا Mesoporous رقيقة لاكتشاف العلامات البيولوجية

The identification of circulating biomarkers holds great potential for non invasive approaches in early diagnosis and prognosis, as well as for the ...

Hollow Microneedle-based Sensor for Multiplexed Transdermal Electrochemical Sensing

The development of a minimally invasive multiplexed monitoring system for rapid analysis of biologically-relevant molecules could offer individuals suffering from chronic medical conditions facile assessment of their immediate physiological state. Furthermore, it could serve as a research tool for analysis of complex, multifactorial medical conditions. In order for such a multianalyte sensor to be realized, it must be minimally invasive, sampling of interstitial fluid must occur without pain or harm to the user, and analysis must be rapid as well as selective.
Initially developed for pain-free drug delivery, microneedles have been used to deliver vaccines and pharmacologic agents (e.g., insulin) through the skin.1-2 Since these devices access the interstitial space, microneedles that are integrated with microelectrodes can be used as transdermal electrochemical sensors. Selective detection of glucose, glutamate, lactate, hydrogen peroxide, and ascorbic acid has been demonstrated using integrated microneedle-electrode devices with carbon fibers, modified carbon pastes, and platinum-coated polymer microneedles serving as transducing elements.3-7,8
This microneedle sensor technology has enabled a novel and sophisticated analytical approach for in situ and simultaneous detection of multiple analytes. Multiplexing offers the possibility of monitoring complex microenvironments, which are otherwise difficult to characterize in a rapid and minimally invasive manner. For example, this technology could be utilized for simultaneous monitoring of extracellular levels of, glucose, lactate and pH,9 which are important metabolic indicators of disease states7,10-14 (e.g., cancer proliferation) and exercise-induced acidosis.15

This article details the construction of a multiplexed microneedle-based sensor. The device is being developed for in situ sampling and electrochemical analysis of multiple analytes in a rapid and selective manner. We envision clinical medicine and biomedical research uses for these microneedle-based sensors.

أجوف Microneedle المستندة إلى الاستشعار عن تعدد في الإرسال الاستشعار الكهروكيميائية عبر الجلد

The development of a minimally invasive multiplexed monitoring system for rapid analysis of biologically-relevant molecules could offer individuals ...

Mass Cytometry: Protocol for Daily Tuning and Running Cell Samples on a CyTOF Mass Cytometer

In recent years, the rapid analysis of single cells has commonly been performed using flow cytometry and fluorescently-labeled antibodies. However, the issue of spectral overlap of fluorophore emissions has limited the number of simultaneous probes. In contrast, the new CyTOF mass cytometer by DVS Sciences couples a liquid single-cell introduction system to an ICP-MS.1 Rather than fluorophores, chelating polymers containing highly-enriched metal isotopes are coupled to antibodies or other specific probes.2-5 Because of the metal purity and mass resolution of the mass cytometer, there is no "spectral overlap" from neighboring isotopes, and therefore no need for compensation matrices. Additionally, due to the use of lanthanide metals, there is no biological background and therefore no equivalent of autofluorescence. With a mass window spanning atomic mass 103-203, theoretically up to 100 labels could be distinguished simultaneously. Currently, more than 35 channels are available using the chelating reagents available from DVS Sciences, allowing unprecedented dissection of the immunological profile of samples.6-7
Disadvantages to mass cytometry include the strict requirement for a separate metal isotope per probe (no equivalent of forward or side scatter), and the fact that it is a destructive technique (no possibility of sorting recovery). The current configuration of the mass cytometer also has a cell transmission rate of only ~25%, thus requiring a higher input number of cells.
Optimal daily performance of the mass cytometer requires several steps. The basic goal of the optimization is to maximize the measured signal intensity of the desired metal isotopes (M) while minimizing the formation of oxides (M+16) that will decrease the M signal intensity and interfere with any desired signal at M+16. The first step is to warm up the machine so a hot, stable ICP plasma has been established. Second, the settings for current and make-up gas flow rate must be optimized on a daily basis. During sample collection, the maximum cell event rate is limited by detector efficiency and processing speed to 1000 cells/sec. However, depending on the sample quality, a slower cell event rate (300-500 cells/sec) is usually desirable to allow better resolution between cells events and thus maximize intact singlets over doublets and debris. Finally, adequate cleaning of the machine at the end of the day helps minimize background signal due to free metal.

The steps necessary for daily tuning and optimization of the performance of a CyTOF mass cytometer are described. Comments on optimal sample preparation and flow rate are discussed

الخلوي الجماعي: بروتوكول لضبط اليومية وعينات الخلايا تشغيل عداد الكريات الشامل على CyTOF

In recent years, the rapid analysis of single cells has commonly been performed using flow cytometry and fluorescently-labeled antibodies. However, the ...

Determination of the Transport Rate of Xenobiotics and Nanomaterials Across the Placenta using the ex vivo Human Placental Perfusion Model

Decades ago the human placenta was thought to be an impenetrable barrier between mother and unborn child. However, the discovery of thalidomide-induced birth defects and many later studies afterwards proved the opposite. Today several harmful xenobiotics like nicotine, heroin, methadone or drugs as well as environmental pollutants were described to overcome this barrier. With the growing use of nanotechnology, the placenta is likely to come into contact with novel nanoparticles either accidentally through exposure or intentionally in the case of potential nanomedical applications. Data from animal experiments cannot be extrapolated to humans because the placenta is the most species-specific mammalian organ 1. Therefore, the ex vivo dual recirculating human placental perfusion, developed by Panigel et al. in 1967 2 and continuously modified by Schneider et al. in 1972 3, can serve as an excellent model to study the transfer of xenobiotics or particles.
Here, we focus on the ex vivo dual recirculating human placental perfusion protocol and its further development to acquire reproducible results.
The placentae were obtained after informed consent of the mothers from uncomplicated term pregnancies undergoing caesarean delivery. The fetal and maternal vessels of an intact cotyledon were cannulated and perfused at least for five hours. As a model particle fluorescently labelled polystyrene particles with sizes of 80 and 500 nm in diameter were added to the maternal circuit. The 80 nm particles were able to cross the placental barrier and provide a perfect example for a substance which is transferred across the placenta to the fetus while the 500 nm particles were retained in the placental tissue or maternal circuit. The ex vivo human placental perfusion model is one of few models providing reliable information about the transport behavior of xenobiotics at an important tissue barrier which delivers predictive and clinical relevant data.

Determination of the Transport Rate of Xenobiotics and Nanomaterials Across the Placenta using the ex vivo Human Placental Perfusion Model

The ex vivo dual recirculating human placental perfusion model can be used to investigate the transfer of xenobiotics and nanoparticles across the human placenta. In this video protocol we describe the equipment and techniques required for a successful execution of a placenta perfusion.

تحديد معدل النقل من الاكسيوبيوتك والمواد النانوية عبر المشيمة باستخدام<em&gt; خارج الحي</em&gt; الإنسان المشيمة الإرواء الموديل

Decades ago the human placenta was thought to be an impenetrable barrier between mother and unborn child. However, the discovery of thalidomide-induced ...

Rapid and Low-cost Prototyping of Medical Devices Using 3D Printed Molds for Liquid Injection Molding

Biologically inert elastomers such as silicone are favorable materials for medical device fabrication, but forming and curing these elastomers using traditional liquid injection molding processes can be an expensive process due to tooling and equipment costs. As a result, it has traditionally been impractical to use liquid injection molding for low-cost, rapid prototyping applications. We have devised a method for rapid and low-cost production of liquid elastomer injection molded devices that utilizes fused deposition modeling 3D printers for mold design and a modified desiccator as an injection system. Low costs and rapid turnaround time in this technique lower the barrier to iteratively designing and prototyping complex elastomer devices. Furthermore, CAD models developed in this process can be later adapted for metal mold tooling design, enabling an easy transition to a traditional injection molding process. We have used this technique to manufacture intravaginal probes involving complex geometries, as well as overmolding over metal parts, using tools commonly available within an academic research laboratory. However, this technique can be easily adapted to create liquid injection molded devices for many other applications.

We have devised a method for low-cost and rapid prototyping of liquid elastomer rubber injection molded devices by using fused deposition modeling 3D printers for mold design and a modified desiccator as a liquid injection system.

النماذج الأولية السريعة ومنخفضة التكلفة من الأجهزة الطبية عن طريق 3D المطبوعة لقوالب حقن صب السائل

Biologically inert elastomers such as silicone are favorable materials for medical device fabrication, but forming and curing these elastomers using ...

Multicolor Fluorescence Detection for Droplet Microfluidics Using Optical Fibers

Fluorescence assays are the most common readouts used in droplet microfluidics due to their bright signals and fast time response. Applications such as multiplex assays, enzyme evolution, and molecular biology enhanced cell sorting require the detection of two or more colors of fluorescence. Standard multicolor detection systems that couple free space lasers to epifluorescence microscopes are bulky, expensive, and difficult to maintain. In this paper, we describe a scheme to perform multicolor detection by exciting discrete regions of a microfluidic channel with lasers coupled to optical fibers. Emitted light is collected by an optical fiber coupled to a single photodetector. Because the excitation occurs at different spatial locations, the identity of emitted light can be encoded as a temporal shift, eliminating the need for more complicated light filtering schemes. The system has been used to detect droplet populations containing four unique combinations of dyes and to detect sub-nanomolar concentrations of fluorescein.

Multicolor fluorescence detection in droplet microfluidics typically involves bulky and complex epifluorescence microscope-based detection systems. Here we describe a compact and modular multicolor detection scheme that utilizes an array of optical fibers to temporally encode multicolor data collected by a single photodetector.

متعدد الألوان كشف الإسفار عن القطرة على microfluidics عن طريق الألياف البصرية

Fluorescence assays are the most common readouts used in droplet microfluidics due to their bright signals and fast time response. Applications such as ...

Synthesis of Cationized Magnetoferritin for Ultra-fast Magnetization of Cells

Many important biomedical applications, such as cell imaging and remote manipulation, can be achieved by labeling cells with superparamagnetic iron oxide nanoparticles (SPIONs). Achieving sufficient cellular uptake of SPIONs is a challenge that has traditionally been met by exposing cells to elevated concentrations of SPIONs or by prolonging exposure times (up to 72 hr). However, these strategies are likely to mediate toxicity. Here, we present the synthesis of the protein-based SPION magnetoferritin as well as a facile surface functionalization protocol that enables rapid cell magnetization using low exposure concentrations. The SPION core of magnetoferritin consists of cobalt-doped iron oxide with an average particle diameter of 8.2 nm mineralized inside the cavity of horse spleen apo-ferritin. Chemical cationization of magnetoferritin produced a novel, highly membrane-active SPION that magnetized human mesenchymal stem cells (hMSCs) using incubation times as short as one minute and iron concentrations as lows as 0.2 mM.

A protocol for the synthesis and cationization of cobalt-doped magnetoferritin is presented, as well as a method to rapidly magnetize stem cells with cationized magnetoferritin.

توليف Cationized Magnetoferritin للمغنطة فائقة السرعة من الخلايا

Many important biomedical applications, such as cell imaging and remote manipulation, can be achieved by labeling cells with superparamagnetic iron oxide ...

Synthesis of Infectious Bacteriophages in an E. coli-based Cell-free Expression System

A new generation of cell-free transcription-translation (TXTL) systems, engineered to have a greater versatility and modularity, provide novel capabilities to perform basic and applied sciences in test tube reactions. Over the past decade, cell-free TXTL has become a powerful technique for a broad range of novel multidisciplinary research areas related to quantitative and synthetic biology. The new TXTL platforms are particularly useful to construct and interrogate biochemical systems through the execution of synthetic or natural gene circuits. In vitro TXTL has proven convenient to rapidly prototype regulatory elements and biological networks as well as to recapitulate molecular self-assembly mechanisms found in living systems. In this article, we describe how infectious bacteriophages, such as MS2 (RNA), &#934;&#935;174 (ssDNA), and T7 (dsDNA), are entirely synthesized from their genome in one-pot reactions using an all Escherichia coli, cell-free TXTL system. Synthesis of the three coliphages is quantified using the plaque assay. We show how the yield of synthesized phage depends on the biochemical settings of the reactions. Molecular crowding, emulated through a controlled concentration of PEG 8000, affects the amount of synthesized phages by orders of magnitudes. We also describe how to amplify the phages and how to purify their genomes. The set of protocols and results presented in this work should be of interest to multidisciplinary researchers involved in cell-free synthetic biology and bioengineering.

Synthesis of Infectious Bacteriophages in an E. coli-based Cell-free Expression System

A new generation of cell-free transcription-translation platforms has been engineered to construct biochemical systems in vitro through the execution of gene circuits. In this article, we describe how bacteriophages, such as MS2, &#934;&#935;174, and T7, are synthesized from their genome using an all E. coli cell-free TXTL system.

توليف "باكتيريوفاجيس المعدية" في كولاي-استناداً إلى "نظام التعبير" الخلية الحرة

A new generation of cell-free transcription-translation (TXTL) systems, engineered to have a greater versatility and modularity, provide novel ...

An Ultrahigh-throughput Microfluidic Platform for Single-cell Genome Sequencing

Sequencing technologies have undergone a paradigm shift from bulk to single-cell resolution in response to an evolving understanding of the role of cellular heterogeneity in biological systems. However, single-cell sequencing of large populations has been hampered by limitations in processing genomes for sequencing. In this paper, we describe a method for single-cell genome sequencing (SiC-seq) which uses droplet microfluidics to isolate, amplify, and barcode the genomes of single cells. Cell encapsulation in microgels allows the compartmentalized purification and tagmentation of DNA, while a microfluidic merger efficiently pairs each genome with a unique single-cell oligonucleotide barcode, allowing &gt;50,000 single cells to be sequenced per run. The sequencing data is demultiplexed by barcode, generating groups of reads originating from single cells. As a high-throughput and low-bias method of single-cell sequencing, SiC-seq will enable a broader range of genomic studies targeted at diverse cell populations.

Single-cell sequencing reveals genotypic heterogeneity in biological systems, but current technologies lack the throughput necessary for the deep profiling of community composition and function. Here, we describe a microfluidic workflow for sequencing &gt;50,000 single-cell genomes from diverse cell populations.

منصة موائع جزيئية أولتراهيغ الإنتاجية لتسلسل جينوم خلية واحدة

Sequencing technologies have undergone a paradigm shift from bulk to single-cell resolution in response to an evolving understanding of the role of ...

Human Neural Organoids for Studying Brain Cancer and Neurodegenerative Diseases

The lack of relevant in vitro neural models is an important obstacle on medical progress for neuropathologies. Establishment of relevant cellular models is crucial both to better understand the pathological mechanisms of these diseases and identify new therapeutic targets and strategies. To be pertinent, an in vitro model must reproduce the pathological features of a human disease. However, in the context of neurodegenerative disease, a relevant in vitro model should provide neural cell replacement as a valuable therapeutic opportunity. 
Such a model would not only allow screening of therapeutic molecules but also can be used to optimize neural protocol differentiation [for example, in the context of transplantation in Parkinson's disease (PD)]. This study describes two in vitro protocols of 1) human glioblastoma development within a human neural organoids (NO) and 2) neuron dopaminergic (DA) differentiation generating a three-dimensional (3D) organoid. For this purpose, a well-standardized protocol was established that allows the production of size-calibrated neurospheres derived from human embryonic stem cell (hESC) differentiation. The first model can be used to reveal molecular and cellular events occurring during in glioblastoma development within the neural organoid, while the DA organoid not only represents a suitable source of DA neurons for cell therapy in Parkinson's disease but also can be used for drug testing.

This study introduces and describes protocols to derive two specific human neural organoids&#160;as a relevant and accurate model for studying 1) human glioblastoma development within human neural organoids exclusively in humans and 2) neuron dopaminergic differentiation generating a three-dimensional organoid.

الأعضاء العصبية البشرية لدراسة سرطان الدماغ والأمراض العصبية

The lack of relevant in vitro neural models is an important obstacle on medical progress for neuropathologies. Establishment of relevant cellular models ...