この研究は、国立癌研究所 (R01CA166376 ・ D.X. ・ グエンに R01CA191489) と国防総省 (W81XWH-16-1-0227 D.X. グエンに) からの助成金によって賄われていた。

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</ol>

著者は競合する金銭的な利益を宣言しません。

印象的な臨床の平行線は、肺癌と肺36の他の慢性疾患と記載されています。特に、特発性肺線維症 (IPF) 患者は、肺癌の増加好みを有しこの協会の歴史37,38を喫煙とは無関係です。IPF は、肺のアーキテクチャと ECM39の析出による呼吸機能の低下の進歩的な破壊によって特徴付けられます。また、外科的切除に続い?...

肺癌は主要ながんの原因関連死亡世界中1。肺癌患者は転移から最終的に屈する遠い器官、特に中枢神経系、肝臓、副腎、骨2,3,4。胸部の悪性腫瘍は、伝統的に小細胞肺癌 (SCLC) または非小細胞肺癌 (NSCLC) がん5として分類されています。非小細胞肺癌は、最も頻繁に悪性腫瘍の診断、肺腺癌 (LUAD) 肺扁平上皮癌 (LUSC)6など、さまざまな組織学的サブタイプに分割することができます。切除人間原発性肺癌のゲノム解析は、指定された histotype 内腫瘍では多様な分子の摂動、さらに彼らの発散の臨床進行に貢献し、患者の予後を交絡を表すことも明らかにしました。肺癌の顕著な不均一性は、合理的な設計、前臨床テスト、および効果的な治療戦略の実装に重要な挑戦を表します。その結果、多様な携帯電話の起源、分子サブタイプ、およびこの病気の段階を検討する難治性肺癌モデルのレパートリーを拡大する必要性があります。
モデル動物を用いた様々 なアプローチは肺癌生体内で、それぞれ独自の長所と短所の興味の生物的質問によって研究に採用されています。遺伝子組み換えマウス モデル (GEMMs) は腫瘍免疫ホスト7その中その結果特定の前駆細胞の種類に特定の遺伝子変異をターゲットできます。臨床的に関連する、非常に強力な GEMMs に関連付けられている待機時間、変動、および/または肺の腫瘍罹患率が特定の定量的計測と遠隔臓器8後期段階転移の検出に法外なことができます。補完的なアプローチという肺癌細胞、マウス腫瘍から直接を取得もしくは派生文化では、確立されたセルラインとして最初は同系のホストに再導入された同種移植モデルの使用であります。同様に肺癌異種移植片は、ひと細胞または患者の派生腫瘍サンプルから確立されます。ひと細胞ライン異種移植片または患者派生異種移植片 (PDXs) 免疫不全マウスにおける一般的に維持され、したがって完全な免疫監視9を排除します。この欠点にもかかわらず、人間 biospecimens 研究基礎的体内プロパティ GEMM 腫瘍よりもより複雑なゲノム異常のためエンコードひと癌細胞の量を制限することを伝達する道を提供します。
同種および異種移植片の 1 つの便利なプロパティは、がん幹細胞 (TICs) 悪性細胞人口10以内の頻度を定量化する採用、制限する従来の細胞希釈アッセイに従うことです。これらの実験で定義されたセル数は動物の側腹部に皮下し、チックの頻度は腫瘍を取る率に基づいて推定できます。皮下腫瘍しかしより低酸素11でき肺腫瘍微小環境のキーの生理学的な制約はモデル化されないことがあります。マウスの肺に上皮幹・前駆細胞気管内配信は、肺と気道幹細胞生物学12を勉強する方法です。ただし、肺が損傷、ウイルス感染13,14などの生理学的なフォームを受ける最初でない限りこの手法から生着率は比較的低いできます。炎症性間質細胞からのサポートおよび/または肺基底膜の中断は、遠位気道15に関連する幹細胞ニッチに移植細胞の保持を向上させる可能性があります。誘導剤の線維化がすることができます誘導多能性細胞16および17間葉系幹細胞の生着を強化する肺を事前条件も。気道損傷のようなフォームが生着率を適用できるかどうか、腫瘍開始容量と肺癌細胞の伸長がまだ体系的に評価します。
本研究では事前の負傷でマウスの肺をコンディショニングすることで同所性同種肺がん細胞生着の効率を上げる方法をについて説明します。LUAD にこれらの癌は、しばしば予後不良19と相関線維性間質18の開発の重要なサブセットと遠位気道で発生します。自然リボソーム ハイブリッド ペプチド-ポリケチド、ブレオマイシンはマウス20肺線維化を誘導するために広く利用されています。ブレオマイシンの気道注入は最初上皮消耗戦肺胞の炎症細胞、マクロファージ、好中球と単球21の募集を推進しています。遠位気道基底膜再編成22,23細胞外マトリックス (ECM) 蒸着24組織の改造現象が続きます。ほとんどの研究25で 30 日後に解決する線維症単一ブレオマイシン投与の効果は一時的なもの。同種および異種移植腫瘍モデルを用いた場合 LUAD 肺細胞の取る速度が大きく向上できるプレコンディショニング ブレオマイシンとマウスの気道をテストしました。

<table><tbody><tr><td>Bleomycin</td><td>Sigma</td><td>B5507-15UN</td><td>CAUTION Health hazard GHS08</td></tr><tr><td>Exel Catheter 24G</td><td>Fisher</td><td>1484121</td><td>Remove needle. For intratracheal injection</td></tr><tr><td>Ketamine (Ketaset inl 100 mg/mL C3N 10 mL)</td><td>Butler Schein</td><td>56344</td><td>To anesthetize mice</td></tr><tr><td>Xylazine</td><td>Butler Schein</td><td>33198</td><td>To anesthetize mice</td></tr><tr><td>Ketoprofen, 5,000 mg</td><td>Cayman Chemical</td><td>10006661</td><td>Analgesic</td></tr><tr><td>Puralube Veterinary Ophthalmic Ointment</td><td>BUTLER ANIMAL HEALTH COMPANY LLC</td><td>8897</td><td>To prevent eye dryness while under anesthesia</td></tr><tr><td>D-Luciferin powder</td><td>Perkin Elmer Health Sciences Inc</td><td>122799</td><td>For luminescent imaging. Reconstitute powder with PBS for a working concentration of 15mg/mL. Protect from Light</td></tr><tr><td>Rodent Intubation stand</td><td>Braintree Scientific</td><td>RIS-100</td><td>Recommended stand for intratracheal injection</td></tr><tr><td>MI-150 ILLUMINATOR 150W MI-150</td><td>DOLAN-JENNER INDUSTRIES</td><td>MI-150 / EEG2823M</td><td>To illuminate and visualize trachea</td></tr><tr><td>Graefe Forceps, 2.75 (7 cm) long serrat</td><td>Roboz</td><td>RS-5111</td><td>For intratracheal injection</td></tr><tr><td>Syringe Luer-Lok Sterile 5ml</td><td>BD / Fisher</td><td>309646</td><td></td></tr><tr><td>Satiny Smooth by Conair Dual Foil Wet/Dry Rechargeable Shaver</td><td>Conair</td><td>-</td><td>To shave mice</td></tr><tr><td>Bonn Scissors, 3.5&quot; straight 15 mm sharp/sharp sure cut blades</td><td>Roboz</td><td>RS-5840SC</td><td></td></tr><tr><td>15 mL conical tube</td><td>BD / Fisher</td><td>352097</td><td></td></tr><tr><td>1.5 mL centrifuge tubes</td><td>USA SCIENTIFIC INC</td><td>1615-5500</td><td></td></tr><tr><td>Vial Scintillation 7 mL Borosilicate Glass GPI</td><td>Fisher</td><td>701350</td><td></td></tr><tr><td>Filter pipette tips (200 &amp;mu;L)</td><td>USA SCIENTIFIC INC</td><td>1120-8710</td><td></td></tr><tr><td>Phosphate Buffered Saline</td><td>Life Technologies</td><td>14190-144</td><td></td></tr><tr><td>0.25% Trypsin-EDTA</td><td>Life Technologies</td><td>25200-056</td><td></td></tr><tr><td>DMEM high glucose</td><td>Life Technologies</td><td>11965-092</td><td></td></tr><tr><td>RPMI Medium 1640</td><td>Life Technologies</td><td>11875-093</td><td></td></tr><tr><td>Fetal bovine serum USDA</td><td>Life Technologies</td><td>10437-028</td><td></td></tr><tr><td>Penicillin-Streptomycin</td><td>Life Technologies</td><td>15140-122</td><td></td></tr><tr><td>Amphotericin B</td><td>Sigma</td><td>A2942-20ML</td><td></td></tr><tr><td>Trypan Blue Stain 0.4%</td><td>Life Technologies</td><td>15250-061</td><td></td></tr><tr><td>Countess Automated Cell Counter</td><td>Life Technologies</td><td>AMQAX1000</td><td></td></tr><tr><td>Flask T/C 75cm sq canted neck, blue cap</td><td>Fisher / Corning</td><td>353135</td><td></td></tr><tr><td>IVIS Spectrum Xenogen Bioluminiscence</td><td>Perkin Elmer Health Sciences Inc</td><td>124262</td><td>For &lt;em&gt;in vivo&lt;/em&gt; bioluminescence imaging</td></tr><tr><td>Living image software</td><td>Perkin Elmer Health Sciences Inc</td><td>128113</td><td>For &lt;em&gt;in vivo&lt;/em&gt; bioluminescence analysis</td></tr><tr><td>XGI-8 Gas Anesthesia System</td><td>Perkin Elmer Health Sciences Inc</td><td>118918</td><td>For Isoflurane anesthesia</td></tr><tr><td>BD Ultra-Fine II Short Needle Insulin Syringe 1 cc. 31 G x 8 mm (5/16 in)</td><td>BD / Fisher</td><td>BD328418</td><td>For retro-orbital luciferin injection</td></tr><tr><td>Syringe 1ml</td><td>BD / Fisher</td><td>14-823-434</td><td>For intraperitoneal injections</td></tr><tr><td>26 G x 1/2 in. needle</td><td>BD / Fisher</td><td>305111</td><td>For intraperitoneal injections</td></tr><tr><td>4% Paraformaldehyde</td><td>VWR</td><td>43368-9M</td><td>CAUTION Health hazard GHS07, GHS08. For fixing tissue</td></tr><tr><td>Pipet-Lite Pipette, Unv. SL-200XLS+</td><td>METTLER-TOLEDO INTERNATIONAL</td><td>17014411</td><td></td></tr><tr><td>Mayer&#039;s Hematoxylin</td><td>ELECTRON MICROSCOPY SCIENCES</td><td>517-28-2</td><td></td></tr><tr><td>Eosin Y stain 0.25% (w/v) in 57%</td><td>Fisher</td><td>67-63-0</td><td></td></tr><tr><td>Masson Trichrome Stain Kit</td><td>IMEB Inc</td><td>K7228</td><td>For masson trichrome stain to visualize collagen</td></tr><tr><td>Superfrost plus glass slides</td><td>Fisher</td><td>1255015</td><td></td></tr><tr><td>6 well plate</td><td>Corning</td><td>C3516</td><td></td></tr><tr><td>Universal Mycoplasma Detection Kit</td><td>ATCC</td><td>30-1012K</td><td></td></tr><tr><td>OCT Embedding compound</td><td>ELECTRON MICROSCOPY SCIENCES</td><td>62550-12</td><td>For embedding tissue for frozen sections</td></tr><tr><td>Leica CM3050 S Research Cryostat</td><td>Leica</td><td>CM3050 S</td><td>To section tissue for staining analysis</td></tr><tr><td>Keyence All-in One Fluorescence Microscope</td><td>Keyence</td><td>BZ-X700</td><td></td></tr><tr><td>ImageJ</td><td>US National Institutes of Health</td><td>IJ1.46</td><td>http://rsbweb.nih.gov/ij/ download.html</td></tr><tr><td>Prism 7.0 for Mac OS X</td><td>GraphPad Software, Inc.</td><td>-</td><td></td></tr><tr><td>Athymic (Crl:NU(NCr)-Foxn1nu) mice</td><td>Charles River</td><td>NIH-553</td><td></td></tr><tr><td>NSG (NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ) mice</td><td>Jackson Laboratories</td><td>5557</td><td></td></tr><tr><td>B6129SF1/J mice</td><td>Jackson Laboratories</td><td>101043</td><td></td></tr><tr><td>NIH-H2030 cells</td><td>ATCC</td><td>CRL-5914</td><td></td></tr><tr><td>368T1</td><td>generously provided by Monte Winslow (Standford University)</td><td>-</td><td></td></tr><tr><td>PC9 cells</td><td>Nguyen DX et al. Cell. 2009;138:51&amp;ndash;62</td><td>-</td><td></td></tr><tr><td>H2030 BrM3 cells</td><td>Nguyen DX et al. Cell. 2009;138:51&amp;ndash;62</td><td>-</td><td></td></tr></tbody></table>

pre-conditioning the airways of mice with bleomycin increases the efficiency of orthotopic lung cancer cell engraftment

肺がんは、異種生物である致命的な治療難治性の疾患です。理解し胸部悪性腫瘍の完全な臨床スペクトルを効果的に治療するには、多様な人間の肺の癌のサブタイプとステージを要約することができます追加の動物モデルが必要です。同種または異種移植モデルは多目的、発癌性容量の生体内で、マウスやひと由来の悪性細胞を用いた定量化を有効にします。ただし、マウス細胞の肺への同所性同種移植の非効率性のためのフランクなどの非生理的サイトで肺のがん細胞の生着の上記の方法を行った。本研究ではあらかじめ線維症誘導エージェント ブレオマイシンとマウスの気道をコンディショニングすることで同所性同種肺がん細胞生着を強化する方法をについて説明します。概念実証実験としてマウスの系統にマウスまたは人的情報源から得られた肺腺癌のサブタイプの腫瘍細胞を接がへのこのアプローチを適用されます。我々 は腫瘍細胞の注入前にブレオマイシンと気道が負傷 0-17 から腫瘍細胞の生着が増加を示す 71 100%。大幅にこのメソッドが強化されたは、肺腫瘍の発生率と異なるモデルとマウス系統を使用して後続の副産物。さらに、明らかな移植肺癌細胞を関連する遠隔臓器に肺から発信します。したがって、我々 はの確立し、肺癌の細胞またはラットの量を制限することの新しい直交異方性モデルを維持し、肺癌細胞生理学的に関連する設定での発癌性の能力を定量的に評価するために使用できるプロトコルを提供します。.

LUAD マウスの肺に癌細胞移植の効率を高めるには、まず事前条件を同所性同種腫瘍細胞の注入 (図 1) に続いてブレオマイシンを使用して航空プロトコルを開発しました。無胸腺を免疫不全マウスに投与した際にもブレオマイシンによる一時的な線維症気道アーキテクチャと増加のコラーゲン沈着 (図 2) の損失によって証明?...

Watch this Scientific Journal Video about Pre-Conditioning the Airways of Mice with Bleomycin Increases the Efficiency of Orthotopic Lung Cancer Cell Engraftment at JoVE.com

Pre-Conditioning the Airways of Mice with Bleomycin Increases the Efficiency of Orthotopic Lung Cancer Cell Engraftment

事前の負傷で気道をコンディショニングすることでマウスの肺に肺癌細胞の同所性同種移植を大幅に強化する手法について述べる。このアプローチは肺微小環境、転移播種、肺癌併存、間質相互作用の研究にも適用可能性があり、派生した異種移植片をより効率的に患者を生成します。

同所性同種肺がん細胞生着の効率を高めるブレオマイシンとマウスの気道をプレコンディショニング

Lung cancer is a deadly treatment refractory disease that is biologically heterogeneous. To understand and effectively treat the full clinical spectrum of ...

pre-conditioning-airways-mice-with-bleomycin-increases-efficiency

Research

JoVE Journal

Medicine

13.6K ビュー.  Yale University School of Medicine. 事前の負傷で気道をコンディショニングすることでマウスの肺に肺癌細胞の同所性同種移植を大幅に強化する手法について述べる。このアプローチは肺微小環境、転移播種、肺癌併存、間質相互作用の研究にも適用可能性があり、派生した異種移植片をより効率的に患者を生成します。

ビデオ: Pre-Conditioning the Airways of Mice with Bleomycin Increases the Efficiency of Orthotopic Lung Cancer Cell Engraftment

Bronchial Thermoplasty:  A Novel Therapeutic Approach to Severe Asthma

Bronchial thermoplasty is a non-drug procedure for severe persistent asthma that delivers thermal energy to the airway wall in a precisely controlled manner to reduce excessive airway smooth muscle. Reducing airway smooth muscle decreases the ability of the airways to constrict, thereby reducing the frequency of asthma attacks. Bronchial thermoplasty is delivered by the Alair System and is performed in three outpatient procedure visits, each scheduled approximately three weeks apart. The first procedure treats the airways of the right lower lobe, the second treats the airways of the left lower lobe and the third and final procedure treats the airways in both upper lobes. After all three procedures are performed the bronchial thermoplasty treatment is complete.
Bronchial thermoplasty is performed during bronchoscopy with the patient under moderate sedation. All accessible airways distal to the mainstem bronchi between 3 and 10 mm in diameter, with the exception of the right middle lobe, are treated under bronchoscopic visualization. Contiguous and non-overlapping activations of the device are used, moving from distal to proximal along the length of the airway, and systematically from airway to airway as described previously. Although conceptually straightforward, the actual execution of bronchial thermoplasty is quite intricate and procedural duration for the treatment of a single lobe is often substantially longer than encountered during routine bronchoscopy. As such, bronchial thermoplasty should be considered a complex interventional bronchoscopy and is intended for the experienced bronchoscopist. Optimal patient management is critical in any such complex and longer duration bronchoscopic procedure. This article discusses the importance of careful patient selection, patient preparation, patient management, procedure duration, postoperative care and follow-up to ensure that bronchial thermoplasty is performed safely.
Bronchial thermoplasty is expected to complement asthma maintenance medications by providing long-lasting asthma control and improving asthma-related quality of life of patients with severe asthma. In addition, bronchial thermoplasty has been demonstrated to reduce severe exacerbations (asthma attacks) emergency rooms visits for respiratory symptoms, and time lost from work, school and other daily activities due to asthma.

Bronchial thermoplasty is a non-drug procedure for severe persistent asthma that delivers thermal energy to the airway wall in a precisely controlled manner to reduce excessive airway smooth muscle. Reducing airway smooth muscle decreases the ability of the airways to constrict, thereby reducing the frequency of asthma attacks.

気管支熱形成術：重篤な喘息の新しい治療アプローチ

Bronchial thermoplasty is a non-drug procedure for severe persistent asthma that delivers thermal energy to the airway wall in a precisely controlled ...

医学

Noninvasive Intratracheal Intubation to Study the Pathology and Physiology of Mouse Lung

The use of a model that mimics the condition of lung diseases in humans is critical for studying the pathophysiology and/or etiology of a particular disease and for developing therapeutic intervention. With the increasing availability of knockout and transgenic derivatives, together with a vast amount of genetic information, mice provide one of the best models to study the molecular mechanisms underlying the pathology and physiology of lung diseases. Inhalation, intranasal instillation, intratracheal instillation, and intratracheal intubation are the most widely used techniques by a number of investigators to administer materials of interest to mouse lungs. There are pros and cons for each technique depending on the goals of a study. Here a noninvasive intratracheal intubation method that can directly deliver exogenous materials to mouse lungs is presented. This technique was applied to administer bleomycin to mouse lungs as a model to study pulmonary fibrosis.

The use of a model that mimics the condition of lung diseases in humans is critical for studying the pathophysiology and/or etiology of a particular disease and for developing therapeutic intervention. Here a noninvasive intratracheal intubation method that can directly deliver exogenous materials to mouse lungs is presented.

マウス肺の病理生理学を研究するための非侵襲的気管内挿管

The use of a model that mimics the condition of lung diseases in humans is critical for studying the pathophysiology and/or etiology of a particular ...

A Multimodal Imaging Approach Based on Micro-CT and Fluorescence Molecular Tomography for Longitudinal Assessment of Bleomycin-Induced Lung Fibrosis in Mice

Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease characterized by the progressive and irreversible destruction of lung architecture, which causes significant deterioration in lung function and subsequent death from respiratory failure.
The pathogenesis of IPF in experimental animal models has been induced by bleomycin administration. In this study, we investigate an IPF-like mouse model induced by a double intratracheal bleomycin instillation. Standard histological assessments used for studying lung fibrosis are invasive terminal procedures. The goal of this work is to monitor lung fibrosis through noninvasive imaging techniques such as Fluorescent Molecular Tomography (FMT) and Micro-CT. These two technologies validated with histology findings could represent a revolutionary functional approach for real time non-invasive monitoring of IPF disease severity and progression. The fusion of different approaches represents a step further for understanding the IPF disease, where the molecular events occurring in a pathological condition can be observed with FMT and the subsequent anatomical changes can be monitored by Micro-CT.

We describe a non-invasive multimodal imaging approach based on Micro-CT and fluorescence molecular tomography for longitudinal assessment of the mouse lung fibrosis model induced by double intratracheal instillation of bleomycin.

マウスにおけるブレオマイシン誘発肺線維症の縦断的評価マイクロ CT と蛍光分子トモグラフィーに基づくマルチ モーダル イメージング手法

Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease characterized by the progressive and irreversible destruction of lung architecture, which ...

免疫・感染学

An Improved Method for Rapid Intubation of the Trachea in Mice

Despite some anatomical and physiological differences, mouse models continue to be an essential tool for studying human lung disease. Bleomycin toxicity is a commonly used model to study both acute lung injury and fibrosis, and multiple methods have been developed for administering bleomycin (and other toxic agents) into the lungs. However, many of these approaches, such as transtracheal instillation, have inherent drawbacks, including the need for strong anesthetics and survival surgery. This paper reports a quick, reproducible method of intratracheal intubation that involves mild inhaled anesthesia, visualization of the trachea, and the use of a surrogate spirometer to confirm exposure. As a proof of concept, 8-12 week old C57BL/6 mice were administered either 2.0 U/kg of bleomycin or an equivalent volume of PBS, and both damage and fibrotic endpoints were measured post-exposure. This procedure allows researchers to treat a large cohort of mice in a relatively short period with little expense and minimal post-procedure care.

This article presents a rapid and simple method for administering bleomycin directly into the mouse trachea via intubation. Key advantages of this method are that it is highly reproducible, easy to master, and does not require specialized equipment or lengthy recovery times.

マウスの気管の迅速な挿管のための改善された方法

Despite some anatomical and physiological differences, mouse models continue to be an essential tool for studying human lung disease. Bleomycin toxicity ...

Induction of Mouse Lung Injury by Endotracheal Injection of Bleomycin

Pulmonary fibrosis is a hallmark of several human lung diseases with a different etiology. Since current therapies are rather limited, mouse models continue to be an essential tool for developing new antifibrotic strategies. Here we provide an effective method to investigate in vivo antifibrotic activity of human mesenchymal stromal cells obtained from whole umbilical cord (hUC-MSC) in attenuating bleomycin-induced lung injury. C57BL/6 mice receive a single endotracheal injection of bleomycin (1.5 U/kg body weight) followed by a double infusion of hUC-MSC (2.5 x 105) into the tail vein, 24 h and 7 days after the bleomycin administration. Upon sacrifice at days 8, 14, or 21, inflammatory and fibrotic changes, collagen content, and hUC-MSC presence in explanted lung tissue are analyzed. The injection of bleomycin into the mouse&#160;trachea allows the direct targeting of the lungs, leading to extensive pulmonary inflammation and fibrosis. The systemic administration of a double dose of hUC-MSC results in the early blunting of the bleomycin-induced lung injury. Intravenously infused hUC-MSC are transiently engrafted into the mouse lungs, where they exert their anti-inflammatory and antifibrotic activity. In conclusion, this protocol has been successfully applied for the preclinical testing of hUC-MSC in an experimental mouse model of human pulmonary fibrosis. However, this technique can be easily extended both to study the effect of different endotracheally administered substances on the pathophysiology of the lungs and to validate new anti-inflammatory and antifibrotic systemic therapies.

Here we present an effective method to investigate the antifibrotic activity of intravenously infused human mesenchymal stromal cells obtained from the whole umbilical cord following the induction of lung injury by an endotracheal injection of bleomycin in C57BL/6 mice. This protocol can be easily extended to the preclinical testing of other therapeutics.

ブレオマイシンの気管内注射によるマウス肺損傷の誘導

Pulmonary fibrosis is a hallmark of several human lung diseases with a different etiology. Since current therapies are rather limited, mouse models ...

Direct Intrabronchial Administration to Improve the Selective Agent Deposition Within the Mouse Lung

Intratracheal (IT) administration of experimental agents is an essential technique in murine models of diffuse lung diseases, such as bleomycin-induced pulmonary fibrosis.&#160; However, distribution of intratracheally-administered agents to the distal mouse lung is often asymmetric, with lung parenchymal concentrations increased in the smaller (but equally accessible) left lung of the mouse.&#160; Described in this report is a novel intrabronchial (IB) approach to cannulate the left and/or right lungs of living mice non-operatively.&#160; It is also demonstrated how this approach can be used to selectively administer agents to one lung or adapted (via dose-adjusted IB delivery) to improve the left-right symmetry of lung delivery of experimental agents, thereby improving models of diffuse lung disease such as bleomycin-induced pulmonary fibrosis.

Intratracheal (IT) administration of experimental agents in mice often results in asymmetric delivery to the distal lungs.&#160; In this report, we describe a direct intrabronchial (IB) approach to cannulate each lung in living mice non-operatively.&#160; This approach can be used to selectively administer agents to one lung or may be adapted to improve the symmetric agent delivery to both lungs.

マウス肺内の選択的剤沈着を改善するための直接気管支内投与

Intratracheal (IT) administration of experimental agents is an essential technique in murine models of diffuse lung diseases, such as bleomycin-induced ...

Adoptive Transfer of IL-33-Stimulated Macrophages into Bleomycin-Induced Mouse Models to Study Their Effect on Idiopathic Pulmonary Fibrosis In Vivo

The inflammatory response caused by early lung injury is one of the important causes of the development of idiopathic pulmonary fibrosis (IPF), which is accompanied by the activation of inflammatory cells such as macrophages and neutrophils, as well as the release of inflammatory factors including TNF-&#945;, IL-1&#946;, and IL-6. Early inflammation caused by activated pulmonary interstitial macrophages (IMs) in response to IL-33 stimulation is known to play a vital role in the pathological process of IPF. This protocol describes the adoptive transfer of IMs stimulated by IL-33 into the lungs of mice to study IPF development. It involves the isolation and culture of primary IMs from host mouse lungs, followed by the adoptive transfer of stimulated IMs into the alveoli of bleomycin (BLM)-induced IPF recipient mice (which have been previously depleted of alveolar macrophages by treatment with clodronate liposomes), and the pathological evaluation of those mice. The representative results show that the adoptive transfer of IL-33-stimulated macrophages aggravates pulmonary fibrosis in mice, suggesting that the establishment of the macrophage adoptive transfer experiment is a good technical means to study IPF pathology.

Adoptive Transfer of IL-33-Stimulated Macrophages into Bleomycin-Induced Mouse Models to Study Their Effect on Idiopathic Pulmonary Fibrosis In Vivo

This protocol describes the isolation of pulmonary interstitial macrophages (IMs) and their adoptive transfer after IL-33 stimulation of the lung alveoli in a mouse model, which can facilitate the in vivo study of idiopathic pulmonary fibrosis (IPF).

IL-33刺激マクロファージのブレオマイシン誘導マウスモデルへの養子導入によるin vivo特発性肺線維症への影響の研究(英語)

The inflammatory response caused by early lung injury is one of the important causes of the development of idiopathic pulmonary fibrosis (IPF), which is ...

A Mouse Model of Pulmonary Fibrosis Induced by Nasal Bleomycin Nebulization

Pulmonary fibrosis is characteristic of several human lung diseases that arise from various causes. Given that treatment options are fairly limited, mouse models continue to be an important tool for developing new anti-fibrotic strategies. In this study, intrapulmonary administration of bleomycin (BLM) is carried out by nasal nebulization to create a mouse model of pulmonary fibrosis that closely mimics clinical disease characteristics. C57BL/6 mice received BLM (7 U/mL, 30 min/day) by nasal nebulization for 3 consecutive days and were sacrificed on day 9, 16, or 23 to observe inflammatory and fibrotic changes in lung tissue. Nasal aerosolized BLM directly targeted the lungs, resulting in widespread and uniform lung inflammation and fibrosis. Thus, we successfully generated an experimental mouse model of typical human pulmonary fibrosis. This method could easily be used to study the effects of the administration of various nasal aerosols on lung pathophysiology and validate new anti-inflammatory and anti-fibrotic treatments.

<meta charset="utf8"></head><body>鼻ブレオマイシン噴霧により誘発される肺線維症のマウスモデル

Various animal models of pulmonary fibrosis have been established using bleomycin to clarify the pathogenesis of pulmonary fibrosis and find new drug targets. However, most pulmonary fibrosis models targeting lung tissue have uneven drug administration. Here, we propose a model of uniform pulmonary fibrosis induced by nasal bleomycin nebulization.

鼻ブレオマイシン噴霧により誘発される肺線維症のマウスモデル

Pulmonary fibrosis is characteristic of several human lung diseases that arise from various causes. Given that treatment options are fairly limited, mouse ...

生物学

Oropharyngeal Administration of Bleomycin in the Murine Model of Pulmonary Fibrosis

Interstitial lung disease (ILD) represents a broad spectrum of disorders characterized by the progressive and often irreversible scarring of the lung parenchyma, the most common being idiopathic pulmonary fibrosis (IPF). Several animal models of IPF have been developed, with the bleomycin murine model being the most widely used. Bleomycin is a chemotherapeutic known to induce DNA damage in the alveolar epithelium, resulting in acute lung injury and pulmonary fibrosis in humans. Rodent models of IPF use bleomycin administration via various methods, the most common being intratracheal (IT). Recently, the oropharyngeal aspiration (OA) technique has been shown to be equally efficacious as IT for multiple fibrosing agents, with considerably fewer side effects and an easier route of delivery. This protocol details the OA method of bleomycin delivery into the murine lung and highlights examples of potential downstream applications for data quantification. This methodology offers a simple, quick, and safe way to utilize this widely used animal model for studying the molecular mechanisms underlying IPF.

This protocol demonstrates the oropharyngeal aspiration technique for use in the bleomycin murine model of pulmonary fibrosis.

肺線維症のマウスモデルにおけるブレオマイシンの中咽頭投与

Interstitial lung disease (ILD) represents a broad spectrum of disorders characterized by the progressive and often irreversible scarring of the lung ...

同所性同種肺がん細胞生着の効率を高めるブレオマイシンとマウスの気道をプレコンディショニング

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気管支熱形成術：重篤な喘息の新しい治療アプローチ

マウス肺の病理生理学を研究するための非侵襲的気管内挿管

マウスにおけるブレオマイシン誘発肺線維症の縦断的評価マイクロ CT と蛍光分子トモグラフィーに基づくマルチモーダルイメージング手法

マウスの気管の迅速な挿管のための改善された方法

ブレオマイシンの気管内注射によるマウス肺損傷の誘導

マウス肺内の選択的剤沈着を改善するための直接気管支内投与

IL-33刺激マクロファージのブレオマイシン誘導マウスモデルへの養子導入によるin vivo特発性肺線維症への影響の研究(英語)

鼻ブレオマイシン噴霧により誘発される肺線維症のマウスモデル

鼻ブレオマイシン噴霧により誘発される肺線維症のマウスモデル

肺線維症のマウスモデルにおけるブレオマイシンの中咽頭投与

同所性同種肺がん細胞生着の効率を高めるブレオマイシンとマウスの気道をプレコンディショニング

要約

さらに動画を探す

気管支熱形成術：重篤な喘息の新しい治療アプローチ

マウス肺の病理生理学を研究するための非侵襲的気管内挿管

マウスにおけるブレオマイシン誘発肺線維症の縦断的評価マイクロ CT と蛍光分子トモグラフィーに基づくマルチ モーダル イメージング手法

マウスの気管の迅速な挿管のための改善された方法

ブレオマイシンの気管内注射によるマウス肺損傷の誘導

マウス肺内の選択的剤沈着を改善するための直接気管支内投与

IL-33刺激マクロファージのブレオマイシン誘導マウスモデルへの養子導入によるin vivo特発性肺線維症への影響の研究(英語)

鼻ブレオマイシン噴霧により誘発される肺線維症のマウスモデル

鼻ブレオマイシン噴霧により誘発される肺線維症のマウスモデル

肺線維症のマウスモデルにおけるブレオマイシンの中咽頭投与

マウスにおけるブレオマイシン誘発肺線維症の縦断的評価マイクロ CT と蛍光分子トモグラフィーに基づくマルチモーダルイメージング手法