이 연구는 국립 암 연구소 (R01CA166376 및 D.X. 구 엔에 R01CA191489)와 국방부 (W81XWH-16-1-0227 D.X. 구 엔 하)에서 교부 금에 의해 투자 되었다.

<ol>
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저자 아무 경쟁 금융 관심사를 선언합니다.

눈에 띄는 임상 유사물 폐암 및 폐36의 다른 만성 질환 사이 문서화 되었습니다. 특히, 환자 특 발성 폐 섬유 증 (IPF) 개발 폐암에 대 한 증가 취향이 있고이 협회는 독립적인 역사37,38흡연의. IPF 폐 건축과 ECM39의 증 착을 통해 장애인된 호흡 기능의 진보적인 파괴에 의해 특징입니다. 또한, 외과 절제술 다음 초기 단계 N...

폐암은 주요 원인의 암 관련 사망 세계1. 폐암 환자 결국 굴복 하는 전이에서 먼 장기에, 특히 중앙 신경 조직, 간, 부 신 분 비, 및 뼈2,,34. 흉부 악성 작은 세포 폐 암 (SCLC) 또는 비 작은 세포 폐 암 (NSCLC)5전통적으로 분류 되어 있다. NSCLC 이며 가장 자주 암 진단 폐 선 암 (LUAD)와 폐 편평 상피 세포 암 (LUSC)6을 포함 하 여 다른 조직학 하위로 세분화 될 수 있습니다. 절제 인간의 기본 폐 암의 게놈 분석 주어진된 histotype 내 종양 또한 다양 한 분자 섭, 더 그들의 분기 임상 진행에 기여 하 고 환자의 예 후를 혼동을 표현할 수 있는 공개 했다. 폐 암의 놀라운이 합리적인 디자인, 전 임상 테스트 및 효과적인 치료 전략의 구현에 중요 한 도전을 나타냅니다. 따라서, 다양 한 세포 기원, 분자 하위,이 질병의 단계를 공부 하 고 온순한 실험 폐 암 모델의 레 퍼 토리를 확장 하는 필요가 있다.
동물 모델을 사용 하 여 다양 한 접근 폐 암에서 공부 vivo에서, 각각의 생물 학적 질문에 따라 그들의 자신의 장단점을 고용 했습니다. 유전자 조작된 마우스 모델 (GEMMs) 주어진된 조상 세포 유형, 종양 immunocompetent 호스트7그 진행 결과에 특정 유전 변경 대상 수 있습니다. 매우 강력 하 고 임상 관련, 대기 시간, 변화, 및 폐 종양 사망률 GEMMs와 관련 된 특정 양적 측정 및 먼 장기8에 늦게 단계 전이의 탐지 금지 될 수 있습니다. 상호 보완적인 접근 이식 모델, 폐 암 세포, 마우스 종양에서 직접 하거나 문화, 설립된 셀 라인으로 먼저 파생 된 syngeneic 호스트에 다시 도입 이다 그것에 의하여의 사용 이다. 비슷하게, 폐 암 xenografts 인간 세포 선 또는 환자 파생된 종양 샘플에서 설정 됩니다. 인간 세포 선 xenografts 또는 환자 파생된 xenografts (PDXs)는 일반적으로 immunocompromised 쥐에서 하 고 따라서 완전 한 면역 감시9배제. 이 결점에도 불구 하 고 그들은 인간 biospecimens 연구 기본적인 vivo에서 속성과 GEMM 종양 보다 더 복잡 한 게놈 착오에 대 한 인코딩 인간 암 세포의 양의 제한 전파 하는 수단을 제공 합니다.
이식 및 xenografts 하나의 유용한 속성은 전통적인 제한 셀 희석 분석 실험, 종양 세포 (TICs)을 시작 하는 악성 세포 인구10의 주파수 척도를 고용 의무가 다는 것. 이 실험에서 셀의 정의 수는 동물의 측면으로 피하 주입 하 고 TICs의 주파수를 종양 걸릴 속도에 따라 예상할 수 있는. 그러나 피하 종양은 더 hypoxic11 수 있으며 폐 종양 microenvironment의 주요 생리 적인 제약을 모델링 하지 않을 수 있습니다. 쥐의 폐에 상피 줄기 또는 조상 세포의 Intratracheal 배달 폐 중생과 기도 줄기 세포 생물학12공부 하는 방법입니다. 그러나,이 기술은에서 engraftment 속도 폐 손상, 바이러스 감염13,14등의 생리 적 형태를 먼저 받게 됩니다 않는 한 상대적으로 낮은 수 있습니다. 자극적인 stromal 세포에서 지원 및 폐 지하실 막의 장애 원심 항공15벽 감 관련 줄기 세포로 이식된 세포의 보존을 높일 수 있습니다. 에이전트를 유도 하는 섬유 증 폐 engraftment 유도 만능 세포16 및17중간 엽 줄기 세포 강화에 사전 조건 또한 수 있습니다. 비슷한 형태의 기도 부상 engraftment 속도 영향을 미칠 수 있습니다, 여부를 종양 시작 용량 및 폐 암 세포의 파생물은 아직 체계적으로 평가 한다.
이 연구에서 우리는 사전 조건 부상으로 쥐의 폐에 의해 orthotopic 폐 암 세포 engraftment의 효율성을 증가 하는 방법을 설명 합니다. LUAD는 수시로 빈약한 예 지19와 상관 관계가 거리 기질18 개발이 암의 중요 한 하위 집합으로 원심 항공에서 발생 한다. Bleomycin polyketide-자연 nonribosomal 하이브리드 펩 티 드은 쥐20에 폐 섬유 증을 유도 하기 위해 광범위 하 게 이용 되어. Bleomycin의 기도 점 먼저 상피 마찰을 포에 염증 세포, 대 식 세포, 호 중구, monocytes21등의 채용을 승진 시킨다. 이것은 원심 항공, 지하실 멤브레인 개편22,23 , 세포 외 기질 (ECM) 증 착24에 개장 하는 조직에 의해 선행 된다. 대부분 연구25에서 30 일 후 해결 하는 섬유 증과 단일 bleomycin 주입의 효과 일시적 이며, 이식 및이 종이 식 모델을 사용 하 여, 사전 조건 bleomycin와 쥐의 기도 폐에서 LUAD 셀의 포획 률 증가 크게 수 테스트.

<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

폐 암은 생물학적으로 이기종은 치명적인 치료 내 화 질병입니다. 이해 하 고 효과적으로 치료 흉부 악성의 전체 임상 스펙트럼, 다양 한 인간의 폐 암 하위 유형 및 단계 정리 수 추가적인 동물 모델 필요 합니다. 이식 또는 종이 식 모델 다재 다능 하 고 tumorigenic 용량에 vivo에서, murine 또는 인간 기원의 악성 세포를 사용 하 여의 정량화를 활성화. 그러나, 폐 암 세포 engraftment의 앞에서 설명한 방법 orthotopic 이식 세포는 폐로의 비 효율으로 인해 마우스의 측면 등 생리 적 비 사이트에서 수행 되었습니다. 이 연구에서 우리가 미리 섬유 증 유도 에이전트 bleomycin와 쥐의 기도 조절 하 여 orthotopic 폐 암 세포 engraftment를 강화 하는 방법을 설명 합니다. 개념 증명 실험으로 우리 쥐의 다양 한 긴장으로 마우스 또는 인간의 소스에서 얻은 폐 선 암 하위의 종양 세포를 engraft에이 접근을 적용. 우리는 0-17에서 종양 세포의 engraftment 증가 종양 세포 주입 전에 bleomycin과 항공 부상 입증 71-100% %. 상당히,이 방법은 폐 종양 발생과 이후의 파생물을 다른 모델 및 마우스 긴장을 사용 하 여 향상. 또한, engrafted 폐 암 세포 관련 먼 장기로는 폐에서 보급. 따라서, 설정 하 고 셀 또는 biospecimen의 양의 제한 폐암의 새로운 orthotopic 모델을 유지 하 고 양적 폐 암 세포 생리학 관련 설정에서의 tumorigenic 용량을 평가 하기 위해 사용할 수 있는 프로토콜 제공 .

LUAD 암 세포 engraftment 쥐의 폐에의 효율성 증가, 우리는 먼저 사전 조건 항공 bleomycin orthotopic 종양 세포 주입 (그림 1) 다음을 사용 하 여 프로토콜 개발. 우리는 immunocompromised athymic 마우스에 투여 하는 경우에 bleomycin 과도 섬유 증에 의해 유도 된 하루 14 기도 건축과 증가 교원 질 공 술 서 (그림 2)의 손실에 의해 입증으로 확인 했...

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

상해 항공을 미리 조절 하 여 murine 폐에 폐 암 세포의 orthotopic engraftment를 크게 향상 하는 방법을 설명 합니다. 이 방법은 또한 폐 microenvironment, 전이성 보급, 폐 암 공동 morbidities stromal 상호 작용 연구에 적용 될 수 있습니다 그리고 파생 xenografts 환자를 보다 효율적으로 생성 하.

Orthotopic 폐 암 세포 Engraftment의 효율성 증가 사전 조건 Bleomycin와 쥐의 기도

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

13.5K 조회수.  Yale University School of Medicine. 상해 항공을 미리 조절 하 여 murine 폐에 폐 암 세포의 orthotopic engraftment를 크게 향상 하는 방법을 설명 합니다. 이 방법은 또한 폐 microenvironment, 전이성 보급, 폐 암 공동 morbidities stromal 상호 작용 연구에 적용 될 수 있습니다 그리고 파생 xenografts 환자를 보다 효율적으로 생성 하.

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

Development of Obliterative Bronchiolitis in a Murine Model of Orthotopic Lung Transplantation

Orthotopic lung transplantation in rats was first reported by Asimacopoulos and colleagues in 1971 1. Currently, this method is well accepted and standardized not only for the study of allo-rejection but also between syngeneic strains for examining mechanisms of ischemia-reperfusion injury after lung transplantation. Although the application of the rat and other large animal model 2 contributed significantly to the elucidation of these studies, the scope of those investigations is limited by the scarcity of knockout and transgenic rats. Due to no effective therapies for obliterative bronchiolitis, the leading cause of death in lung transplant patients, there has been an intensive search for pre-clinical models that replicate obliterative bronchiolitis. The tracheal allograft model is the most widely used and may reproduce some of the histopathologic features of obliterative bronchiolitis 3. However, the lack of an intact vasculature with no connection to the recipient's conducting airways, and incomplete pathologic features of obliterative bronchiolitis limit the utility of this model 4. Unlike transplantation of other solid organs, vascularized mouse lung transplants have only recently been reported by Okazaki and colleagues for the first time in 2007 5. Applying the basic principles of the rat lung transplant, our lab initiated the obliterative bronchiolitis model using minor histoincompatible antigen murine orthotopic single-left lung transplants which allows the further study of obliterative bronchiolitis immunopathogenesis6.

Obliterative bronchiolitis is the key impediment to the long-term survival of lung transplant recipients and the lack of a robust preclinical model precludes examining obliterative bronchiolitis immunopathogenesis. Unlike other solid organ transplants, vascularized mouse lung transplantation has only recently been developed. Here we show our independently developed obliterative bronchiolitis model after murine orthotopic single-lung transplantation.

Orthotopic 폐 이식의 Murine 모델에 Obliterative Bronchiolitis의 개발

Orthotopic lung transplantation in rats was first reported by Asimacopoulos and colleagues in 1971 1. Currently, this method is well accepted and ...

연구

의학

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.

비 침습적 기관 내 삽관 마우스 폐의 병리학 및 생리학을 연구하는

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.

Multimodal 접근을 이미징 Bleomycin 유도 폐 섬유 증 생쥐에서의 경도 평가 대 한 마이크로-CT와 형광 분자 단층에 따라

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

면역학 및 감염병학

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.

마우스의기도 신속 삽관 용 개선 된 방법

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.

Bleomycin의 내시경 주입에 의한 마우스 폐 손상의 유도

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

Implantation and Monitoring by PET/CT of an Orthotopic Model of Human Pleural Mesothelioma in Athymic Mice

Malignant pleural mesothelioma (MPM) is a rare and aggressive tumor arising in the mesothelium that covers the lungs, the heart, and the thoracic cavity. MPM development is mainly associated with asbestos. Treatments provide only modest survival since the median survival average is 9&#8211;18 months from the time of diagnosis. Therefore, more effective treatments must be identified. Most data describing new therapeutic targets were obtained from in vitro experiments and need to be validated in reliable in vivo preclinical models. This article describes one such reliable MPM orthotopic model obtained after injection of a human MPM cell line H2052/484 into the pleural cavity of immunodeficient athymic mice. Transplantation in the orthotopic site allows studying the progression of tumor in the natural in vivo environment. Positron emission tomography/computed tomography (PET/CT) molecular imaging using the clinical [18F]-2-fluoro-2-deoxy-D-glucose ([18F]FDG) radiotracer is the diagnosis method of choice for examining patients with MPM. Accordingly, [18F]FDG-PET/CT was used to longitudinally monitor the disease progression of the H2052/484 orthotopic model. This technique has a high 3R potential (Reduce the number of animals, Refine to lessen pain and discomfort, and Replace animal experimentation with alternatives) since the tumor development can be monitored non-invasively and the number of animals required could be significantly reduced.
This model displays a high development rate, a rapid tumor growth, is cost-efficient and allows for rapid clinical translation. By using this orthotopic xenograft MPM model, researchers can assess biological responses of a reliable MPM model following therapeutic interventions.

This article describes the generation of an orthotopic mouse model of human pleural mesothelioma by implantation of H2052/484 mesothelioma cells into the pleural cavity of immunocompromised athymic mice. The longitudinal monitoring of the development of intrapleural tumors was assessed by non-invasive multimodal [18F]-2-fluoro-2-deoxy-D-glucose positron emission tomography and computed tomography imaging.

심질 마우스에 있는 인간 흉막 중피종의 정형외 모형의 PET/CT에 의한 이식 및 모니터링

Malignant pleural mesothelioma (MPM) is a rare and aggressive tumor arising in the mesothelium that covers the lungs, the heart, and the thoracic cavity. ...

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.

마우스 폐 내 선택적 에이전트 침착을 개선하기 위한 직접 기관내 투여

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).

생체 내에서 특발성 폐 섬유증에 미치는 영향을 연구하기 위해 IL-33 자극 대식세포를 블레오마이신 유도 마우스 모델로 입양 전달

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>비강 Bleomycin 분무에 의해 유도된 폐 섬유증의 마우스 모델

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.

비강 Bleomycin 분무에 의해 유도된 폐 섬유증의 마우스 모델

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

Orthotopic 폐 암 세포 Engraftment의 효율성 증가 사전 조건 Bleomycin와 쥐의 기도

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Orthotopic 폐 이식의 Murine 모델에 Obliterative Bronchiolitis의 개발

비 침습적 기관 내 삽관 마우스 폐의 병리학 및 생리학을 연구하는

Multimodal 접근을 이미징 Bleomycin 유도 폐 섬유 증 생쥐에서의 경도 평가 대 한 마이크로-CT와 형광 분자 단층에 따라

마우스의기도 신속 삽관 용 개선 된 방법

Bleomycin의 내시경 주입에 의한 마우스 폐 손상의 유도

심질 마우스에 있는 인간 흉막 중피종의 정형외 모형의 PET/CT에 의한 이식 및 모니터링

마우스 폐 내 선택적 에이전트 침착을 개선하기 위한 직접 기관내 투여

생체 내에서 특발성 폐 섬유증에 미치는 영향을 연구하기 위해 IL-33 자극 대식세포를 블레오마이신 유도 마우스 모델로 입양 전달

비강 Bleomycin 분무에 의해 유도된 폐 섬유증의 마우스 모델

비강 Bleomycin 분무에 의해 유도된 폐 섬유증의 마우스 모델