Bu çalışma NIH araştırma hibeleri R01AR062207, R01AR061484, R56AI100901, K01AR053210 ve (CJ Liu) Romatoloji Araştırma Vakfı Bir Hastalık Hedefli Araştırma Grant tarafından kısmen desteklenmiştir.

Hayvanlara ilişkin tüm cerrahi prosedür ağrı ve cerrahinin neden rahatsızlığı en aza indirmek için yapılan bir çaba ile yerel Kurumun Hayvan Bakım ve Etik Komitesi tarafından onaylanmış olması gerekir. 1.. Hazırlık <ol><li> Ameliyat için yaklaşık 25 g bir vücut ağırlığına sahip 8-12 haftalık erkek C57BL / 6 fareleri seçin. </li><li> Ksilazin (5 mg / kg) ve ketamin (40 mg / kg) her ikisini de içeren bir kokteyl intraperitonal enjeksiyon yoluyla hayvanlara anestezisi. </li><li> Jilet ile diz tıraş, sonra cerrahi drape hayvan ve betadin ve alkol (3x) ile cerrahi alan sterilize ve bir merhem ile fare gözleri kapsamaktadır. </li></ol> 2. Cerrahi Süreci <ol><li> Diz eklemi ortaya çıkarmak için 1 cm boyuna medial para-patellar kesi olun. </li><li> Patella ve patellar ligamentin lateral çıkığı ile hafifçe diz eklemini açın. <ol><li> Uzunlamasına diz eklem kapsülü KesmeAdım 2.1 &#39;de medial para-patellar kesiden. </li><li> Forseps ile diz eklem kapsülü teşrih. </li><li> Sol el ile arka ayak distal kısmını tut ve forseps ile patella ve patellar ligamentin lateral çıkığı gerçekleştirin. Yavaşça arka pençe tutun ve pençe travmayı önlemek için emin olun. Eklem kapsülü disseke daha iyi, daha az kuvvet çıkığı yapmak gerekecektir. </li></ol></li><li> Kıkırdak yüzeyinin kurumasını önlemek için işlem sırasında eklem kıkırdağı yüzeyinde steril tuzlu su Damla. </li><li> Tibia plato medial menisküs çapa medial meniscotibial bağın kesebiliyor. Medial menisküs altındaki kıkırdak yaralanmasına kaçının. <ol><li> Femur medial kondil ve tibia medial platosu arasında bulur medial menisküs tespit. </li><li> Tibia interkondiler itibar ile medial menisküs lateral tarafını bağlayan meniscotibial bağ tanımlayın. </li><li> Hi tutunnd elinizle hafifçe pençe, ve 10 numaralı cerrahi bıçak kullanarak dikkatlice medial meniscotibial bağın kesti. Kıkırdak ve diğer bağ artiküler zarar neden değil emin olun. Birçok durumda, kaplama yağ yastığı tarafına çekilmesine ancak bağ tespit etmek amacıyla kaldırılması gerek yoktur. </li></ol></li><li> 6-0 emilebilir sütür ile diz eklem kapsülü kapatın. </li><li> 6-0 ipek sütür ile cilt kapatın. </li></ol> 3. Post-operatif Bakım <ol><li> Ameliyat sonrası ağrı en aza indirmek için, her fare ameliyat bölgesinde% 0.25 bupivakain bir damla uygulanır. </li><li> Su ve yiyecek almak için ücretsiz ameliyat fareler bırakın. </li></ol> 4. Cerrahi DMM Modelin histolojik Puanlama <ol><li> Belirtilen zaman noktalarında fareler kurban ameliyattan sonra (örneğin, 4 hafta, 8 hafta ve 12 hafta. Burada temsilcisi olarak 8 haftalık sonuçlar elde edilmiştir.) </li><li> Tüm diz eklemleri, kireçlenmiş, embe sabitparafin ile dded ve daha sonra 5 um aralıklarla seri olarak kesit. <ol><li> No: 10 bıçaklarla bütün arka uzuvları kesilmiş. </li><li> Dikkatlice arka bacaklarda cilt ve kasların incelemek, ve RT 3 gün boyunca% 4 PFA ile numunelerini sabitlemek. </li><li> PFA çıkarın ve su ile örnekleri temizleyin. Daha sonra, 2 hafta boyunca 4 ° C&#39;de EDTA içinde örnekleri kirecini. </li><li> Bir etanol gradyanı içinde örnekleri kurutmak. Ayrıntılı olarak, daha sonra etanol değiştirebilir ve O / N için% 70 etanol içinde yeni bir dizi in örnekleri tutmak, 1 saat boyunca% 70 etanol içinde örnekleri tutmak Daha sonra,% 80 örnekleri koymak ve% 90 etanol dolayısıyla ve O / N% 100 etanol ile, ardından, sırasıyla 1 saat boyunca tutmak </li><li> Etanol çıkarın. 1 saat için ksilen de örnekleri tutmak ve ksilen yeni bir dizi için değiştirin. Bu adım 3x tekrarlayın. </li><li> Leica gömme merkezini kullanarak bir parafin kalıba örnekleri embed. Daha sonra, numuneler bir döner mikrotom (Leica RM225 ile 5 um&#39;lik kesitler edilir5, Almanya) ve daha sonra cam slaytlar üzerine toplandı. </li><li> Seri sagital kesitler kısım, orta kondilin merkezine lateral kondilin merkezi bir bölgeyi kapsayan her bir örnek için kesilir. </li></ol></li><li> Safranin O boyama, gerçekleştirilen önce 25 açıklandığı gibi OARSI skorlama sistemi ile puanlama ve istatistiksel analizi ile takip edilmektedir. <ol><li> İlk olarak, o-ksilen içinde slaytlar deparaffinize ve damıtılmış su, bir etanol gradyanı bunları hidrat. Bundan sonra, slaytlar WEIGERT Demir Hematoxylin Çözüm,% 0.05 Fast Green (FCF) Çözüm,% 1 asetik asit solüsyonu ve% 0.1 Safranin O Çözüm üzerinden lekeli. Reçineli orta kullanarak slaytlar monte edin. </li><li> Histolojik skoru için istatistiksel analiz yapmak, kıkırdak ve kıkırdak yapısında yıkım yüzdesi proteoglycan&#39;ın (kırmızı renk) kaybına dayalı Safranin O lekeli slaytlar Skor. </li></ol></li></ol>

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Biz burada biz herhangi bir çıkar çatışması olmadığını beyan ederim.

Bu farelerin suşu DMM modeli indüksiyonu için, farelerin farklı suşları / O C57BL6, 129/SvInJ ve FVB, ardından 129/SvEv gerginlik en yüksek seviyede, DMM sonra OA şiddeti değişen var çok önemli olduğu bildirilmektedir n 26. DMM nispeten duyarlı biz, bu çalışmada kullanılan fare, - transgenlerin büyük bir kısmı gibi PGRN-/ olarak C57BL6 farelerde kurulmuştur. Transgen tür FVB / N fareleri gibi hassas olmayan gerilme dayanan, ancak bu DMM indüksiyon öncesi duyarlı suşlar ile bu fare...

Ayrıca dejeneratif artrit olarak bilinen Osteoartrit (OA), dünya nüfusunun% 15 etkiler ve Amerika Birleşik Devletleri içinde 46 milyon fazla kişi ve sinovit, kıkırdak dejenerasyonu ve osteofit oluşumu 1 ile karakterizedir. Bu, genetik metabolik, biyomekanik ve biyokimyasal faktörlerin karmaşık etkileşimi sonucu olabilir. OA altında yatan mekanizmaları bilimsel topluluk kaçmasına devam ediyor. OA 2,3 patogenezi taklit edebilir çeşitli hayvan modelleri şu anda vardır. Çünkü çeşitli genetiği değiştirilmiş farelerin kullanılabilirliği ve deney maliyet etkinliği hem farelerde hayvan modelleri kurmak önemlidir. Deneysel OA modellerin farklı türde arasında, medial menisküs (DMM) modeli cerrahiye bağlı istikrarsızlaştırma çünkü onun iyi tekrarlanabilirlik ve OA gelişimi sırasında nispeten daha yavaş ilerlemesinin iyi kabul edilen OA modelidir. Bu özelliklerin her ikisi de varfarklı tedaviler veya transgenlerin 3-8 OA ilerlemesi değerlendirilmesi için önemli olmuştur. Ancak cerrahi OA modelin kıvamı ameliyat sırasında ve bir sonucu olarak çeşitli faktörler tarafından etkilenmektedir, cerrahi fare modelinin uygulama sınırlıdır. Progranulin (PGRN), çeşitli hücrelerde ifade edilen çok fonksiyonlu bir büyüme faktörüdür. Bu PGRN yara iyileşmesi 9, tümör oluşumu 10, 11-15 ve enflamasyon gibi çeşitli fizyolojik ve hastalık süreçlerinde önemli bir rol oynadığı bilinmektedir. Çalışmalar ayrıca PGRN yetersizliği, insan ve fareler 16-18 hem de sinir sisteminin dejeneratif hastalıklara neden olduğunu göstermiştir. Bu PGRN insan mafsal kıkırdağının eksprese olduğu bilinmektedir, ve seviyesi önemli ölçüde OA ve romatoid artrit 19 hastaların kıkırdağında yüksektir. Buna ek olarak, aynı zamanda PGRN kondrosit çoğalması 20, farklılaşması ve bölgelerinde ossifikasyonun de önemli bir rol oynargelişim sırasında 21,22 büyüme plağının kemikleşme. Son zamanlarda, PGRN TNF reseptörlerine bağlanma yoluyla TNF-α antagonize ve enflamatuvar artrit modellerinde 13,14,23,24 bir anti-inflamatuar işlevi sergilediğini rapor etmiştir. Ancak, OA PGRN rolü, özellikle in vivo, bir muamma olarak kalır. - Farelerde yazıda, cerrahi DMM modeli neden ve WT ve PGRN-/ in DMM modelini kurarak OA gelişiminde PGRN rolünü araştırmak için prosedürü sunuyoruz.

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			<td height="21" style="height:21px;width:216px;">No. 10 Surgical blades</td>
			<td style="width:135px;">FEATHER</td>
			<td style="width:119px;">25-2976#10</td>
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			<td height="21" style="height:21px;">6-0 suture</td>
			<td>APPLIED DENTAL</td>
			<td>WG-N53133</td>
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establishment of a surgically-induced model in mice to investigate the protective role of progranulin in osteoarthritis

Medial menisküs destabilizasyon (DMM) modeli, in vivo olarak, osteoartrit (OA) patojenezinde çeşitli artrit ilişkili moleküllerin patofizyolojik rolü incelemek için önemli bir araçtır. Bununla birlikte, detaylı, özellikle de farelerde bu karmaşık bir model kurmak için görsel protokol, mevcut değildir. Bu yazıda yabanitipte ve progranulin (PGRN) yararlandı - / - örnekler farelerde DMM modeli uyarılması için bir protokol ve bu cerrahiye bağlı modelin kurulması aşağıdaki OA karşılaştırıldığında başlangıcı tanıtmak gibi fareler. Fareler üzerinde yapılan işlemler sadece menisco-tibia ligament kesilir ve medial menisküs istikrarsızlaştırma neden eklem kapsülü veya DMM işlemi, açılan sahte işlem, ya da vardı. Osteoartrit şiddeti histolojik analizi (örneğin, Safranin O ile boyanmıştır) OA-ilişkili genlerin ifadesi, hücre dışı matris moleküllerinin kıkırdak bozulması ve osteofit formu kullanılarak değerlendirilmiştirtirme. Fareler ve bu cerrahiye bağlı modelinde daha şiddetli OA fenotipe yol PGNR büyüme faktörü kaybı - DMM işlemi başarıyla yabanitipte ve PGRN-/ hem OA başlamasını ve ilerlemesini bağlı.

DMM model başarılı farelerde kurulan ve PGRN eksikliği cerrahi kaynaklı OA gelişimini abartılı oldu. Fareler - Sham ve DMM işlemleri (Şekil 1) WT ve PGRN-/ gerçekleştirildi. 8 hafta ameliyat sonrası, fareler kurban edildi ve Safranin O lekeleme diz eklem bölümlerinde gerçekleştirilmiştir, histoloji göre artrit puanının istatistiksel analiz takip etmektedir. Şekil 2A&#39;da gösterildiği gibi, benzer temel koşulların?...

Watch this Scientific Journal Video about Establishment of a Surgically-induced Model in Mice to Investigate the Protective Role of Progranulin in Osteoarthritis at JoVE.com

Establishment of a Surgically-induced Model in Mice to Investigate the Protective Role of Progranulin in Osteoarthritis

Biz farelerde medial menisküs (DMM) modeli, osteoartrit (OA) araştırma için etkili bir araç istikrarı bozacak bir protokol açıklar. Buna ek olarak, progranulin OA patogenezinde koruyucu bir rol oynadığını gösteren, bu model kullanılarak progranulincan fahiş OA gelişimi ve ilerlemesinde bu eksikliği göstermiştir.

Osteoartrit Progranulin ve koruyucu rolünü araştırmak için Farelerde bir Cerrahi kaynaklı Modeli Kurulması

Destabilization of medial meniscus (DMM) model is an important tool for studying the pathophysiological roles of numerous arthritis associated molecules ...

establishment-surgically-induced-model-mice-to-investigate-protective

Research

JoVE Journal

Bioengineering

27.1K Görüntüleme.  NYU Hospital for Joint Diseases.  Biz farelerde medial menisküs (DMM) modeli, osteoartrit (OA) araştırma için etkili bir araç istikrarı bozacak bir protokol açıklar. Buna ek olarak, progranulin OA patogenezinde koruyucu bir rol oynadığını gösteren, bu model kullanılarak progranulincan fahiş OA gelişimi ve ilerlemesinde bu eksikliği göstermiştir. 

Video: Establishment of a Surgically-induced Model in Mice to Investigate the Protective Role of Progranulin in Osteoarthritis

Multiparametric Optical Mapping of the Langendorff-perfused Rabbit Heart

Optical imaging and fluorescent probes have significantly advanced research methodology in the field of cardiac electrophysiology in ways that could not have been accomplished by other approaches1. With the use of the calcium- and voltage-sensitive dyes, optical mapping allows measurement of transmembrane action potentials and calcium transients with high spatial resolution without the physical contact with the tissue. This makes measurements of the cardiac electrical activity possible under many conditions where the use of electrodes is inconvenient or impossible1. For example, optical recordings provide accurate morphological changes of membrane potential during and immediately after stimulation and defibrillation, while conventional electrode techniques suffer from stimulus-induced artifacts during and after stimuli due to electrode polarization1. 
The Langendorff-perfused rabbit heart is one of the most studied models of human heart physiology and pathophysiology. Many types of arrhythmias observed clinically could be recapitulated in the rabbit heart model. It was shown that wave patterns in the rabbit heart during ventricular arrhythmias, determined by effective size of the heart and the wavelength of reentry, are very similar to that in the human heart2. It was also shown that critical aspects of excitation-contraction (EC) coupling in rabbit myocardium, such as the relative contribution of sarcoplasmic reticulum (SR), is very similar to human EC coupling3. Here we present the basic procedures of optical mapping experiments in Langendorff-perfused rabbit hearts, including the Langendorff perfusion system setup, the optical mapping systems setup, the isolation and cannulation of the heart, perfusion and dye-staining of the heart, excitation-contraction uncoupling, and collection of optical signals. These methods could be also applied to the heart from species other than rabbit with adjustments to flow rates, optics, solutions, etc.
Two optical mapping systems are described. The panoramic mapping system is used to map the entire epicardium of the rabbit heart4-7. This system provides a global view of the evolution of reentrant circuits during arrhythmogenesis and defibrillation, and has been used to study the mechanisms of arrhythmias and antiarrhythmia therapy8,9. The dual mapping system is used to map the action potential (AP) and calcium transient (CaT) simultaneously from the same field of view10-13. This approach has enhanced our understanding of the important role of calcium in the electrical alternans and the induction of arrhythmia14-16.

This article describes the basic procedures for conducting optical mapping experiments in the Langendorff-perfused rabbit heart using the panoramic imaging system, and the dual (voltage and calcium) imaging modality.

Çok parametreli Langendorff perfüze Tavşan Kalp Optik Haritalama

Optical imaging and fluorescent probes have significantly advanced research methodology in the field of cardiac electrophysiology in ways that could not ...

Biyomühendislik

Creating Two-Dimensional Patterned Substrates for Protein and Cell Confinement

Microcontact printing provides a rapid, highly reproducible method for the creation of well-defined patterned substrates.1 While microcontact printing can be employed to directly print a large number of molecules, including proteins,2 DNA,3 and silanes,4 the formation of self-assembled monolayers (SAMs) from long chain alkane thiols on gold provides a simple way to confine proteins and cells to specific patterns containing adhesive and resistant regions. This confinement can be used to control cell morphology and is useful for examining a variety of questions in protein and cell biology. Here, we describe a general method for the creation of well-defined protein patterns for cellular studies.5 This process involves three steps: the production of a patterned master using photolithography, the creation of a PDMS stamp, and microcontact printing of a gold-coated substrate. Once patterned, these cell culture substrates are capable of confining proteins and/or cells (primary cells or cell lines) to the pattern.
The use of self-assembled monolayer chemistry allows for precise control over the patterned protein/cell adhesive regions and non-adhesive regions; this cannot be achieved using direct protein stamping. Hexadecanethiol, the long chain alkane thiol used in the microcontact printing step, produces a hydrophobic surface that readily adsorbs protein from solution. The glycol-terminated thiol, used for backfilling the non-printed regions of the substrate, creates a monolayer that is resistant to protein adsorption and therefore cell growth.6 These thiol monomers produce highly structured monolayers that precisely define regions of the substrate that can support protein adsorption and cell growth. As a result, these substrates are useful for a wide variety of applications from the study of intercellular behavior7 to the creation of microelectronics.8
While other types of monolayer chemistry have been used for cell culture studies, including work from our group using trichlorosilanes to create patterns directly on glass substrates,9 patterned monolayers formed from alkane thiols on gold are straight-forward to prepare. Moreover, the monomers used for monolayer preparation are commercially available, stable, and do not require storage or handling under inert atmosphere. Patterned substrates prepared from alkane thiols can also be recycled and reused several times, maintaining cell confinement.10

Self-assembled monolayers (SAMs) formed from long chain alkane thiols on gold provide well-defined substrates for the formation of protein patterns and cell confinement. Microcontact printing of hexadecanethiol using a polydimethylsiloxane (PDMS) stamp followed by backfilling with a glycol-terminated alkane thiol monomer produces a pattern where protein and cells adsorb only to the stamped hexadecanethiol region.

Protein ve hücre Etrafının İki Boyutlu Desenli Yüzeyler Oluşturma

Microcontact printing provides a rapid, highly reproducible method for the creation of well-defined patterned substrates.1  While microcontact printing ...

Design of a Cyclic Pressure Bioreactor for the Ex Vivo Study of Aortic Heart Valves

The aortic valve, located between the left ventricle and the aorta, allows for unidirectional blood flow, preventing backflow into the ventricle. Aortic valve leaflets are composed of interstitial cells suspended within an extracellular matrix (ECM) and are lined with an endothelial cell monolayer. The valve withstands a harsh, dynamic environment and is constantly exposed to shear, flexion, tension, and compression. Research has shown calcific lesions in diseased valves occur in areas of high mechanical stress as a result of endothelial disruption or interstitial matrix damage1-3. Hence, it is not surprising that epidemiological studies have shown high blood pressure to be a leading risk factor in the onset of aortic valve disease4. 
The only treatment option currently available for valve disease is surgical replacement of the diseased valve with a bioprosthetic or mechanical valve5. Improved understanding of valve biology in response to physical stresses would help elucidate the mechanisms of valve pathogenesis. In turn, this could help in the development of non-invasive therapies such as pharmaceutical intervention or prevention. Several bioreactors have been previously developed to study the mechanobiology of native or engineered heart valves6-9. Pulsatile bioreactors have also been developed to study a range of tissues including cartilage10, bone11 and bladder12. The aim of this work was to develop a cyclic pressure system that could be used to elucidate the biological response of aortic valve leaflets to increased pressure loads. 
The system consisted of an acrylic chamber in which to place samples and produce cyclic pressure, viton diaphragm solenoid valves to control the timing of the pressure cycle, and a computer to control electrical devices. The pressure was monitored using a pressure transducer, and the signal was conditioned using a load cell conditioner. A LabVIEW program regulated the pressure using an analog device to pump compressed air into the system at the appropriate rate. The system mimicked the dynamic transvalvular pressure levels associated with the aortic valve; a saw tooth wave produced a gradual increase in pressure, typical of the transvalvular pressure gradient that is present across the valve during diastole, followed by a sharp pressure drop depicting valve opening in systole. The LabVIEW program allowed users to control the magnitude and frequency of cyclic pressure. The system was able to subject tissue samples to physiological and pathological pressure conditions. This device can be used to increase our understanding of how heart valves respond to changes in the local mechanical environment.

Design of a Cyclic Pressure Bioreactor for the Ex Vivo Study of Aortic Heart Valves

A cyclic pressure bioreactor capable of subjecting heart valve tissue to physiological and pathological pressure conditions has been designed. A LabVIEW program allows users to control pressure magnitude, amplitude and frequency. This device can be used to study the mechanobiology of heart valve tissue or isolated cells.

Devirli Basınç Biyoreaktör Tasarım Ex vivo</emAort Kalp Vanalar> Eğitim

The aortic valve, located between the left ventricle and the aorta, allows for unidirectional blood flow, preventing backflow into the ventricle. Aortic ...

Quantification of Global Diastolic Function by Kinematic Modeling-based Analysis of Transmitral Flow via the Parametrized Diastolic Filling Formalism

Quantitative cardiac function assessment remains a challenge for physiologists and clinicians.&#160;Although historically invasive methods have comprised the only means available, the development of noninvasive imaging modalities (echocardiography, MRI, CT) having high temporal and spatial resolution provide a new window for quantitative diastolic function assessment. Echocardiography is the agreed upon standard for diastolic function assessment, but indexes in current clinical use merely utilize selected features of chamber dimension (M-mode) or blood/tissue motion (Doppler) waveforms without incorporating the physiologic causal determinants of the motion itself.&#160;The recognition that all left ventricles (LV) initiate filling by serving as mechanical suction pumps allows global diastolic function to be assessed based on laws of motion that apply to all chambers. What differentiates one heart from another are the parameters of the equation of motion that governs filling. Accordingly, development of the Parametrized Diastolic Filling (PDF) formalism&#160;has shown that the entire range of clinically observed early transmitral flow (Doppler E-wave) patterns are extremely well fit by the laws of damped oscillatory motion.&#160;This permits analysis of individual E-waves in accordance with a causal mechanism (recoil-initiated suction) that yields three (numerically) unique lumped parameters whose physiologic analogues are chamber stiffness (k), viscoelasticity/relaxation (c), and load (xo).&#160;The recording of transmitral flow (Doppler E-waves) is standard practice in clinical cardiology and, therefore, the echocardiographic recording method is only briefly reviewed. Our focus is on determination of the PDF parameters from routinely recorded E-wave data.&#160;As the highlighted results indicate, once the PDF parameters have been obtained from a suitable number of load varying E-waves, the investigator is free to use the parameters or construct indexes from the parameters (such as stored energy 1/2kxo2, maximum A-V pressure gradient kxo, load independent index of diastolic function, etc.) and select the aspect of physiology or pathophysiology to be quantified.

Accurate, causality-based quantification of global diastolic function has been achieved by kinematic modeling-based analysis of transmitral flow via the Parametrized Diastolic Filling (PDF) formalism. PDF generates unique stiffness, relaxation,&#160;and load parameters and elucidates &#39;new&#39; physiology while providing sensitive and specific indexes of dysfunction.

Parametrized Diyastolik Dolum Biçimcilik yoluyla Transmitral Akışının Modellenmesi Kinematik tabanlı Analizi ile Küresel Diyastolik Fonksiyonu Kantitasyonu

Quantitative cardiac function assessment remains a challenge for physiologists and clinicians.&#160;Although historically invasive methods have comprised ...

Production, Characterization and Potential Uses of a 3D Tissue-engineered Human Esophageal Mucosal Model

The incidence of both esophageal adenocarcinoma and its precursor, Barrett&#8217;s Metaplasia, are rising rapidly in the western world. Furthermore esophageal adenocarcinoma generally has a poor prognosis, with little improvement in survival rates in recent years. These are difficult conditions to study and there has been a lack of suitable experimental platforms to investigate disorders of the esophageal mucosa.
A model of the human esophageal mucosa has been developed in the MacNeil laboratory which, unlike conventional 2D cell culture systems, recapitulates the cell-cell and cell-matrix interactions present in vivo and produces a mature, stratified epithelium similar to that of the normal human esophagus. Briefly, the model utilizes non-transformed normal primary human esophageal fibroblasts and epithelial cells grown within a porcine-derived acellular esophageal scaffold. Immunohistochemical characterization of this model by CK4, CK14, Ki67 and involucrin staining demonstrates appropriate recapitulation of the histology of the normal human esophageal mucosa.
This model provides a robust, biologically relevant experimental model of the human esophageal mucosa. It can easily be manipulated to investigate a number of research questions including the effectiveness of pharmacological agents and the impact of exposure to environmental factors such as alcohol, toxins, high temperature or gastro-esophageal refluxate components. The model also facilitates extended culture periods not achievable with conventional 2D cell culture, enabling, inter alia, the study of the impact of repeated exposure of a mature epithelium to the agent of interest for up to 20 days. Furthermore, a variety of cell lines, such as those derived from esophageal tumors or Barrett&#8217;s Metaplasia, can be incorporated into the model to investigate processes such as tumor invasion and drug responsiveness in a more biologically relevant environment.

This manuscript describes the production, characterization and potential uses of a tissue engineered 3D esophageal construct prepared from normal primary human esophageal fibroblast and squamous epithelial cells seeded within a de-cellularized porcine scaffold. The results demonstrate the formation of a mature stratified epithelium similar to the normal human esophagus.

3D Doku mühendisliği İnsan Özofagus Mukozal Modeli Üretimi, Karakterizasyonu ve Potansiyel Kullanımları

The incidence of both esophageal adenocarcinoma and its precursor, Barrett&#8217;s Metaplasia, are rising rapidly in the western world. Furthermore ...

Planar Gradient Diffusion System to Investigate Chemotaxis in a 3D Collagen Matrix

The importance of cell migration can be seen through the development of human life. When cells migrate, they generate forces and transfer these forces to their surrounding area, leading to cell movement and migration. In order to understand the mechanisms that can alter and/or affect cell migration, one can study these forces. In theory, understanding the fundamental mechanisms and forces underlying cell migration holds the promise of effective approaches for treating diseases and promoting cellular transplantation. Unfortunately, modern chemotaxis chambers that have been developed are usually restricted to two dimensions (2D) and have complex diffusion gradients that make the experiment difficult to interpret. To this end, we have developed, and describe in this paper, a direct-viewing chamber for chemotaxis studies, which allows one to overcome modern chemotaxis chamber obstacles able to measure cell forces and specific concentration within the chamber in a 3D environment to study cell 3D migration. More compelling, this approach allows one to successfully model diffusion through 3D collagen matrices and calculate the coefficient of diffusion of a chemoattractant through multiple different concentrations of collagen, while keeping the system simple and user friendly for traction force microscopy (TFM) and digital volume correlation (DVC) analysis.

Cell migration is an important part of human development and life. In order to understand the mechanisms that can alter cell migration, we present a planar gradient diffusion system to investigate chemotaxis in a 3D collagen matrix, which allows one to overcome modern diffusion chamber limitations of existing assays.

Planar Gradient Difüzyon Sistemi 3D Kollajen Matrix Kemotaksis Araştırma

The importance of cell migration can be seen through the development of human life. When cells migrate, they generate forces and transfer these forces to ...

An In Vitro Organ Culture Model of the Murine Intervertebral Disc

Intervertebral disc (IVD) degeneration is a significant contributor to low back pain. The IVD is a fibrocartilaginous joint that serves to transmit and dampen loads in the spine. The IVD consists of a proteoglycan-rich nucleus pulposus (NP) and a collagen-rich annulus fibrosis (AF) sandwiched by cartilaginous end-plates. Together with the adjacent vertebrae, the vertebrae-IVD structure forms a functional spine unit (FSU). These microstructures contain unique cell types as well as unique extracellular matrices. Whole organ culture of the FSU preserves the native extracellular matrix, cell differentiation phenotypes, and cellular-matrix interactions. Thus, organ culture techniques are particularly useful for investigating the complex biological mechanisms of the IVD. Here, we describe a high-throughput approach for culturing whole lumbar mouse FSUs that provides an ideal platform for studying disease mechanisms and therapies for the IVD. Furthermore, we describe several applications that utilize this organ culture method to conduct further studies including contrast-enhanced microCT imaging and three-dimensional high-resolution finite element modeling of the IVD.

An In Vitro Organ Culture Model of the Murine Intervertebral Disc

Whole organ culture of the intervertebral disc (IVD) preserves the native extracellular matrix, cell phenotypes, and cellular-matrix interactions. Here we describe an IVD culture system using mouse lumbar and caudal IVDs in their functional spinal units and several applications utilizing this system.

bir<em&gt; İn Vitro</emKemirgen İntervertebral Disk&gt; Organ Kültürü Modeli

Intervertebral disc (IVD) degeneration is a significant contributor to low back pain. The IVD is a fibrocartilaginous joint that serves to transmit and ...

Creating a Structurally Realistic Finite Element Geometric Model of a Cardiomyocyte to Study the Role of Cellular Architecture in Cardiomyocyte Systems Biology

With the advent of three-dimensional (3D) imaging technologies such as electron tomography, serial-block-face scanning electron microscopy and confocal microscopy, the scientific community has unprecedented access to large datasets at sub-micrometer resolution that characterize the architectural remodeling that accompanies changes in cardiomyocyte function in health and disease. However, these datasets have been under-utilized for&#160;investigating the role of cellular architecture remodeling in cardiomyocyte function. The purpose of this protocol is to outline how to create an accurate finite element model of a cardiomyocyte using high resolution electron microscopy and confocal microscopy images. A detailed and accurate model of cellular architecture has significant potential to provide new insights into cardiomyocyte biology, more than experiments alone can garner. The power of this method lies in its ability to computationally fuse information from two disparate imaging modalities of cardiomyocyte ultrastructure to develop one unified and detailed model of the cardiomyocyte. This protocol outlines steps to integrate electron tomography and confocal microscopy images of adult male Wistar (name for a specific breed of albino rat) rat cardiomyocytes to develop a half-sarcomere finite element model of the cardiomyocyte. The procedure generates a 3D finite element model that contains an accurate, high-resolution depiction (on the order of ~35 nm) of the distribution of mitochondria, myofibrils and ryanodine receptor clusters that release the necessary calcium for cardiomyocyte contraction from the sarcoplasmic reticular network (SR) into the myofibril and cytosolic compartment. The model generated here as an illustration does not incorporate details of the transverse-tubule architecture or the sarcoplasmic reticular network and is therefore a minimal model of the cardiomyocyte. Nevertheless, the model can already be applied in simulation-based investigations into the role of cell structure in calcium signaling and mitochondrial bioenergetics, which is illustrated and discussed using two case studies that are presented following the detailed protocol.

This protocol outlines a novel method to create a spatially detailed finite element model of the intracellular architecture of cardiomyocytes from electron microscopy and confocal microscopy images. The power of this spatially detailed model is demonstrated using case studies in calcium signaling and bioenergetics.

Cardiomyocyte sistemleri Biyoloji hücresel mimarisi rolü eğitim için bir Cardiomyocyte bir yapısal olarak gerçekçi Sonlu elemanlar geometrik Model oluşturma

With the advent of three-dimensional (3D) imaging technologies such as electron tomography, serial-block-face scanning electron microscopy and confocal ...

Calorespirometry: A Powerful, Noninvasive Approach to Investigate Cellular Energy Metabolism

Many cell lines used in basic biological and biomedical research maintain energy homeostasis through a combination of both aerobic and anaerobic respiration. However, the extent to which both pathways contribute to the landscape of cellular energy production is consistently overlooked. Transformed cells cultured in saturating levels of glucose often show a decreased dependency on oxidative phosphorylation for ATP production, which is compensated by an increase in substrate-level phosphorylation. This shift in metabolic poise allows cells to proliferate despite the presence of mitochondrial toxins. In neglecting the altered metabolic poise of transformed cells, results from a pharmaceutical screening may be misinterpreted since the potentially mitotoxic effects may not be detected using model cell lines cultured in the presence of high glucose concentrations. This protocol describes the pairing of two powerful techniques, respirometry and calorimetry, which allows for the quantitative and noninvasive assessment of both aerobic and anaerobic contributions to cellular ATP production. Both aerobic and anaerobic respirations generate heat, which can be monitored via calorimetry. Meanwhile, measuring the rate of oxygen consumption can assess the extent of aerobic respiration. When both heat dissipation and oxygen consumption are measured simultaneously, the calorespirometric ratio can be determined. The experimentally obtained value can then be compared to the theoretical oxycaloric equivalent and the extent of the anaerobic respiration can be judged. Thus, calorespirometry provides a unique method to analyze a wide range of biological questions, including drug development, microbial growth, and fundamental bioenergetics under both normoxic and hypoxic conditions.

This protocol describes calorespirometry, the direct and simultaneous measurement of both heat dissipation and respiration, which provides a noninvasive approach to assess energy metabolism. This technique is used to assess the contribution of both aerobic and anaerobic pathways to energy utilization by monitoring the total cellular energy flow.

Calorespirometry: Hücresel enerji metabolizması araştırmak için bir güçlü, invaziv olmayan bir yaklaşım

Many cell lines used in basic biological and biomedical research maintain energy homeostasis through a combination of both aerobic and anaerobic ...

A Tripeptide-Stabilized Nanoemulsion of Oleic Acid

We describe a method to produce a nanoemulsion composed of an oleic acids-Pt(II) core and a lysine-tyrosine-phenylalanine (KYF) coating (KYF-Pt-NE). The KYF-Pt-NE encapsulates Pt(II) at 10 wt. %, has a diameter of 107 &#177; 27 nm and a negative surface charge. The KYF-Pt-NE is stable in water and in serum, and is biologically active. The conjugation of a fluorophore to KYF allows the synthesis of a fluorescent nanoemulsion that is suitable for biological imaging. The synthesis of the nanoemulsion is performed in an aqueous environment, and the KYF-Pt-NE forms via self-assembly of a short KYF peptide and an oleic acids-platinum(II) conjugate. The self-assembly process depends on the temperature of the solution, the molar ratio of the substrates, and the flow rate of the substrate addition. Crucial steps include maintaining the optimal stirring rate during the synthesis, permitting sufficient time for self-assembly, and pre-concentrating the nanoemulsion gradually in a centrifugal concentrator.

This protocol describes an efficient method to synthesize a nanoemulsion of an oleic acids-platinum(II) conjugate stabilized with a lysine-tyrosine-phenylalanine (KYF) tripeptide. The nanoemulsion forms under mild synthetic conditions via self-assembly of the KYF and the conjugate.

Tripeptit stabilize Nanoemulsion oleik asit

We describe a method to produce a nanoemulsion composed of an oleic acids-Pt(II) core and a lysine-tyrosine-phenylalanine (KYF) coating (KYF-Pt-NE). The ...