이 작품은 상 호 W81XWH - 13-2-0053에서, AFIRM II의 노력을 지원하기 위해 육군, 해군, NIH, 공군, VA 보건 업무에 의해 지원되었다. 미국 육군 의학 연구 수집 활동, 820 챈들러 거리, 포트 데 트릭 MD 21702-5014가 수여 및 관리 취득 사무실입니다. 의견, 해석, 결론 및 권고 사항은 저자의 것이며, 반드시 국방부에 의해 승인되지 않습니다. 저자는이 연구 기간 동안 우수한 수의학 지원 제시카 IZZI, DVM, 캐롤라인 개렛, DVM과 줄리 왓슨, DVM에게 감사의 말씀을 전합니다.

모든 실험은 관리 및 국립 보건 연구소 (NIH)의 실험 동물의 사용을위한 설명서에 따라 실시하고, 존스 홉킨스 대학 동물 관리 및 사용위원회 (JHUACUC)에 의해 승인되었다. 구체적인 절차는 승인 ACUC 프로토콜 MO13M108 하에서 수행 하였다. 1. 기부자 운영 <ol><li> 수술하기 전에 각각의 약리학 적 제제에 대한 적절한 시점에서 진통을 관리. 0.1 mg의 프레 노르 핀의 피하의 / kg BW 1 시간 전에 피부 절개에 승인 된 동물 관리 및 사용 프로토콜 사용에 따라. </li><li> 이소 플루 란 침착 도너 4 %의 이소 플루 란 기화기에 부착 된 챔버를 통해인가; 코 콘을 통해 2 %에 진정 및 마취을 유지한다. 절차의 개시에 앞서 마취 깊이를 모니터링하도록 발가락 핀치 움츠림 반사를 수행한다. </li><li> 마스크, 일회용 절연 가운과 장갑을 착용 할 것. </li><li> 수술 아칸소 쉐이브개, 10 % 포비돈과 특히 뒷다리와 사타구니, 그리고 준비에 - 요오드. </li><li> 멸균 필드 드레이프, 멸균 장비 및 고배율 현미경 (40X)를 사용합니다. </li><li> 허벅지 중간 영역 근위 가위를 사용하여 고간 피부 절개를 원주 마우스 본체의 나머지 뒷다리를 구별하기 위해 절개를 연결한다. </li><li> 식별 및 대퇴 동맥, 정맥 신경을 해부하다. 포셉 및 마이크로 가위를 사용하여 세 가지 구조를 분리합니다. </li><li> 척추 경 혈관이 절개되면 마이크로 가위를 사용 사타구니 인대의 수준에서 혈관을 나눈다. </li><li> 다음에, 가위를 사용하여 공여체 동물의 그래프트 별도 허벅지 중간 레벨에서 근위 개별 복부 (박근 및 내측 대퇴부 근육) 및 척수 근육 그룹 (20)을 분할하는 것을 계속한다. </li><li> 대퇴골을 가로로 쪼개다 가위를 사용하여 대퇴골 간부의 중간에서 절단. </li><li> 이소 플루 란 과다 복용 FOL로 동물을 안락사자궁 전위에 의해 lowed. 심장 박동 및 호흡의 중단을 확인합니다. </li><li> 주사기에 장착 된 33 G 플러싱 바늘을 사용하여 헤파린 2 ㎖ (30 IE) 감기 (4 °에 C) 식염수 사지를 플러시 (재료 표 참조). </li><li> 각각 대퇴 정맥과 동맥에 한 폴리이 미드 커프를 배치합니다. </li><li> 삽입 할 때까지 4 ° C에서 배양 접시와 저장소에 젖은면 거즈, 장소에 이식 랩. </li></ol> 2.받는 사람 운영 <ol><li> 뒷다리의 제거 <ol><li> 수술하기 전에 각각의 약리학 적 제제에 대한 적절한 시점에서 진통을 관리. 승인 된 동물 관리 및 사용 프로토콜 사용 부 프레 놀핀 SC 1 시간 이전에 피부 절개 0.1 ㎎ / ㎏ BW에 따라. </li><li> 이소 플루 란 침착 도너 4 %의 이소 플루 란 기화기에 부착 된 챔버를 통해인가; 코 콘을 통해 2 %에 진정 및 마취을 유지한다. 부서를 모니터링 발가락 핀치 철수 반사를 수행절차의 개시에 앞서 마취 H. </li><li> 마취 동안 건조를 방지하기 위해 마우스의 눈에 수의학 연고를 사용합니다. </li><li> 특히, 10 % 포비돈와 뒷다리와 사타구니 준비를 외과 영역을 면도 - 요오드. </li><li> 허벅지 중간 영역 근위 가위를 사용하여 고간 피부 절개를 원주 마우스 본체의 나머지 뒷다리를 구별하기 위해 절개를 연결한다. </li><li> 포셉 및 마이크로 가위를 사용하여 세 가지 구조를 확인하고 대퇴 동맥, 정맥 신경을 해부와 구분합니다. </li><li> 척추 경 혈관이 절개되면 사타구니 인대 레벨 대퇴부 혈관 클램프. </li><li> 표면 상복부 동맥의 수준에서 말초 혈관을 잘라. </li><li> 다음으로, 고유 뒷 리튬을 분리 근위 대퇴부의 중간 레벨에서 개별 복부 (박근 및 내측 대퇴부 근육) 및 척수 근육 그룹 (20)을 분할 계속가위를 사용하여 동물로부터받는 MB. </li><li> 가위를 이용하여 대퇴골 축의 중간 대퇴골 횡단면. </li><li> 절개 부위의 출혈 때문에받는 혈액 손실을 방지하기 위해 이전에 횡단 허벅지의 근육을 소작. </li></ol></li><li> 심기 <ol><li> 따뜻한 식염수 (37 °에 C)와 수술 필드를 관개하고 이전에 0.3 ml의에게 따뜻한 식염수를 주입하고 수술 후 유체 손실을 최소화합니다. </li><li> 받는 사람과 이식의 대퇴골 뼈를 정렬하고 골수로드로 20 G 척추 바늘을 사용하여 연결하여 기본 뒷다리의 정확한 해부학 적 위치를 반영하는 방법으로 이식을 놓습니다. </li><li> Coapt 흡수성 봉합사 (6-0 Polysorb)을 이용하여 복부 및 척수 근육 그룹. </li><li> 비 봉합 커프 기술을 사용하여 대퇴 혈관 연결; 커프 이전 용기에 장착 위에 상세히, 그라프 끝 용기의 수신자 측 당겨티. 10-0 나일론 봉합사를 사용하고 팔목에받는 용기를 해결하기 위해 원주 넥타이를 수행합니다. </li><li> 다음 클램프를 놓습니다. 이 단계에서 시각적 커프 회전 용기의 오 회전 및 꼬임을 방지하는 최적의 위치를​​ 확인. </li><li> 근육받는 도너 인터페이스 뼈 단부에 특히 초점을 전기 소작을 사용 세심한 지혈을 수행한다. </li><li> 비 흡수성 나일론 봉합사 (6-0 에틸 론)를 사용하여 피부를 닫습니다. </li><li> 동물이 가열 램프 아래의 새장에 복구 할 수 있도록하여 정상 체온 조건을 설정합니다. 주택 시설에 반환하기 전에 적어도 4 시간 동안 정기적 인 모니터링을 계속합니다. </li><li> 3 일간를 0.1 mg / kg SC마다 6 ~ 8 시간의 용량 부 프레 놀핀와 수술 후 진통제를 제공합니다. </li></ol></li></ol>

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D., Liu, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Orthotopic+hindlimb+transplantation+in+the+mouse.">Orthotopic hindlimb transplantation in the mouse.</a> J. Reconstr. Microsurg. 19, 49 (2002).</li><li>Tung, T. H., Mohanakumar, T., Mackinnon, S. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Development+of+a+Mouse+Model+for+Heterotopic+Limb+and+Composite-Tissue+Transplantation.">Development of a Mouse Model for Heterotopic Limb and Composite-Tissue Transplantation.</a> J. Reconstr. Microsurg. 17, 267-274 (2001).</li><li>Zhang, F., Shi, D. Y., Kryger, Z., Moon, W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Development+of+a+mouse+limb+transplantation+model.">Development of a mouse limb transplantation model.</a> Microsurgery. 19 (5), 209-213 (1999).</li><li>Schneeberger, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Atypical+acute+rejection+after+hand+transplantation.">Atypical acute rejection after hand transplantation.</a> Am. J. Transplant. 8, 688-696 (2008).</li><li>Mathes, D. W., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Stable+mixed+hematopoietic+chimerism+permits+tolerance+of+vascularized+composite+allografts+across+a+full+major+histocompatibility+mismatch+in+swine.">Stable mixed hematopoietic chimerism permits tolerance of vascularized composite allografts across a full major histocompatibility mismatch in swine.</a> Transpl. Int. 27, 1086-1096 (2014).</li><li>Yamada, Y., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Use+of+CTLA4Ig+for+induction+of+mixed+chimerism+and+renal+allograft+tolerance+in+nonhuman+primates.">Use of CTLA4Ig for induction of mixed chimerism and renal allograft tolerance in nonhuman primates.</a> Am. J. Transplant. 14, 2704-2712 (2014).</li><li>Sachs, D. H., Kawai, T., Sykes, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Induction+of+tolerance+through+mixed+chimerism.">Induction of tolerance through mixed chimerism.</a> Cold Spring Harb. Perspect. Med. 4, a015529 (2014).</li><li>Kawai, T., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=HLA-mismatched+renal+transplantation+without+maintenance+immunosuppression.">HLA-mismatched renal transplantation without maintenance immunosuppression.</a> N. Engl. J. Med. 358, 353-361 (2008).</li><li>Kawai, T., Sachs, D. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Tolerance+induction:+hematopoietic+chimerism.">Tolerance induction: hematopoietic chimerism.</a> Curr Opin Organ Transplant. 18, 402-407 (2013).</li><li>Kawai, T., Sachs, D. H., Sykes, M., Cosimi, A. .. B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=HLA-mismatched+renal+transplantation+without+maintenance+immunosuppression.">HLA-mismatched renal transplantation without maintenance immunosuppression.</a> N. Engl. J. Med. 368, 1850-1852 (2013).</li><li>Leventhal, J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Chimerism+and+tolerance+without+GVHD+or+engraftment+syndrome+in+HLA-mismatched+combined+kidney+and+hematopoietic+stem+cell+transplantation.">Chimerism and tolerance without GVHD or engraftment syndrome in HLA-mismatched combined kidney and hematopoietic stem cell transplantation.</a> Sci. Transl. Med. 4, 124-128 (2012).</li><li>Cendales, L. C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+Banff+2007+working+classification+of+skin-containing+composite+tissue+allograft+pathology.">The Banff 2007 working classification of skin-containing composite tissue allograft pathology.</a> Am. J. Transplant. 8, 1396-1400 (2008).</li></ol>

The authors declare that they have no competing financial interest.

혈관 복합 동종 이식은 이러한 파괴적인 조직 결손의 재건을위한 상지 및 얼굴 이식으로, 기존의 재건 절차를 수정할 수있는없는 환자에 대한 올바른 치료 옵션으로 진화하고있다. 재건 미세 분야의 기술 발전뿐만 아니라 강력한 면역 억제 및 고체 장기 이식에서 면역 조절 성 치료와 광대 한 경험은 지금이 독특한 환자 인구 3,21에서 장기 이식 생존 할 수 있습니다. 그러나, 동종 이식 유?...

The late nineties heralded the pioneering days of reconstructive transplantation with the first successful hand transplant performed in France in 1998. Since then, the use of VCAs for reconstruction of devastating tissue defects has been successfully employed in a wide spectrum of patients. To date, the world counts 76 recipients of 112 upper extremities as well as 31 faces 1-3. In addition, several other types of VCAs such as abdominal wall 4, larynx 5, trachea 6, vascularized joints 7, and even penis 8 have been performed. Furthermore, the live birth of a baby was recently reported after uterus transplantation 9. This growing world experience is indicative for how reconstructive transplantation has become a valid therapeutic option for patients suffering of significant functional tissue defects not amendable to conventional reconstructive and restorative surgery and treatment. 
While the idea of replacing "like with like" sparked clinical enthusiasm, initial skepticism still prevails with regards to side effects of conventional high-dose immunosuppression required to maintain allografts and their function 10,11. However, as shown by seminal work of Lee et al., these composite grafts are less likely to reject than its individual components, and furthermore, some of the tissue components such as the vascularized bone compartment have fueled optimism as they might exert unique immunological effects onto the balance of immune acceptance and rejection 12. 
Our group pioneered several microsurgical animal models for solid organ transplantation, as well as vascularized composite allotransplantation 13-19. Here we describe a novel surgical procedure using a non-suture cuff technique to perform super micro-vascular anastomosis in an orthotopic mouse hind limb transplantation model. This transplant model provides a useful tool for investigating immune acceptance and rejection mechanisms, as well as the role of individual tissue components, such as the vascularized bone marrow compartment, towards tolerance induction in the immunologically versatile setting of the mouse species. Additionally, the orthotopic placement of the limb opens the possibilities for nerve regeneration and functional outcome studies, which are critically important to the setting of VCA.

<table>
	<tbody>
		<tr>
			<td>Suture, 6-0 Nylon</td>
			<td>MWI</td>
			<td>31849</td>
			<td></td>
		</tr>
		<tr>
			<td>Suture, 6-0 Polysorb</td>
			<td>MWI</td>
			<td>72667</td>
			<td></td>
		</tr>
		<tr>
			<td>Suture, 10-0 Nylon</td>
			<td>Aero Surgical</td>
			<td>TK-107038</td>
			<td></td>
		</tr>
		<tr>
			<td>Polyimide Tubing, Size 25</td>
			<td>Vention Medical</td>
			<td>141-0023</td>
			<td></td>
		</tr>
		<tr>
			<td>Polyimide Tubing, Size 27</td>
			<td>Vention Medical</td>
			<td>141-0015</td>
			<td></td>
		</tr>
		<tr>
			<td>Microvascular Clamps (Single)</td>
			<td>Synovis</td>
			<td>00396</td>
			<td></td>
		</tr>
		<tr>
			<td>Microvascular Clamps (Double)</td>
			<td>Synovis</td>
			<td>00414</td>
			<td></td>
		</tr>
		<tr>
			<td>Micro-Scissors</td>
			<td>Synovis</td>
			<td>SAS-18</td>
			<td></td>
		</tr>
		<tr>
			<td>Micro-Forceps</td>
			<td>Synovis</td>
			<td>FRS-15 RM-8</td>
			<td></td>
		</tr>
		<tr>
			<td>Micro-Dilators</td>
			<td>Synovis</td>
			<td>FRS-15 RM-8d.1</td>
			<td></td>
		</tr>
		<tr>
			<td>Micro-Needledriver</td>
			<td>Synovis</td>
			<td>C-14</td>
			<td></td>
		</tr>
		<tr>
			<td>Micro-Clamp Applicator</td>
			<td>Synovis</td>
			<td>CAF-4</td>
			<td></td>
		</tr>
		<tr>
			<td>Micro-Flushing Needle</td>
			<td>Hamilton</td>
			<td>N/A</td>
			<td>10MM, 30&#176;, 33G</td>
		</tr>
		<tr>
			<td>Lactated Ringers Solution</td>
			<td>Fisher Scientific</td>
			<td>NC9968051</td>
			<td></td>
		</tr>
		<tr>
			<td>Buprenorphine</td>
			<td>N/A</td>
			<td>N/A</td>
			<td>DEA Number required; Obtained from hosptial pharmacy.</td>
		</tr>
		<tr>
			<td>Enrofloxacin; Baytril</td>
			<td>Bayer Health Care</td>
			<td>186599</td>
			<td></td>
		</tr>
		<tr>
			<td>Heparin</td>
			<td>N/A</td>
			<td>N/A</td>
			<td>Obtained from hosptial pharmacy</td>
		</tr>
	</tbody>
</table>

orthotopic hind limb transplantation in the mouse

In vivo animal model systems, and in particular mouse models, have evolved into powerful and versatile scientific tools indispensable to basic and translational research in the field of transplantation medicine. A vast array of reagents is available exclusively in this setting, including mono- and polyclonal antibodies for both diagnostic and interventional applications. In addition, a vast number of genotyped, inbred, transgenic, and knock out strains allow detailed investigation of the individual contributions of humoral and cellular components to the complex interplay of an immune response and make the mouse the gold standard for immunological research. 
Vascularized Composite Allotransplantation (VCA) delineates a novel field of transplantation using allografts to replace "like with like" in patients suffering traumatic or congenital tissue loss. This surgical methodological protocol shows the use of a non-suture cuff technique for super-microvascular anastomosis in an orthotopic mouse hind limb transplantation model. The model specifically allows for comparison between established paradigms in solid organ transplantation with a novel form of transplants consisting of various different tissue components. Uniquely, this model allows for the transplantation of a viable vascularized bone marrow compartment and niche that have the potential to exert a beneficial effect on the balance of immune acceptance and rejection. This technique provides a tool to investigate alloantigen recognition and allograft rejection and acceptance, as well as enables the pursuit of functional nerve regeneration studies to further advance this novel field of transplantation.

비 봉합 커프 기술을 사용하여, 마우스 모델에서 혈관 복합 동종 이식을 수행하는도 1에 도시 된 바와 같이 우수한 장기 이식 동물의 생존을 달성 할 수있다. 또한,이 혈관 복합 점진적 동종 이식 거부 반응의 재현 가능한 결과를 수득하는 신뢰할 수있는 방법을 나타낸다 동종 이식도 2에 도시 이미지에 의해 설명 된대로. 거절 더이 쥐 모델에서 동...

Watch this Scientific Journal Video about Orthotopic Hind Limb Transplantation in the Mouse at JoVE.com

Orthotopic Hind Limb Transplantation in the Mouse

슈퍼 미세 혈관 문합을위한 비 봉합 커프 기술을 적용 마우스에서 소성을 뒷다리 이식이 새로운 모델은, 혈관 복합 동종 이식 (VCA)에 관한 생체 역학적 면역 학적 연구를위한 강력한 도구를 제공합니다.

마우스에서 소성을 뒷다리 이식

In vivo animal model systems, and in particular mouse models, have evolved into powerful and versatile scientific tools indispensable to basic and ...

orthotopic-hind-limb-transplantation-in-the-mouse

Research

JoVE Journal

Medicine

11.6K 조회수.  Johns Hopkins University School of Medicine.  슈퍼 미세 혈관 문합을위한 비 봉합 커프 기술을 적용 마우스에서 소성을 뒷다리 이식이 새로운 모델은, 혈관 복합 동종 이식 (VCA)에 관한 생체 역학적 면역 학적 연구를위한 강력한 도구를 제공합니다. 

비디오: Orthotopic Hind Limb Transplantation in the Mouse

Orthotopic Aortic Transplantation: A Rat Model to Study the Development of Chronic Vasculopathy

Research models of chronic rejection are essential to investigate pathobiological and pathophysiological processes during the development of transplant vasculopathy (TVP).
The commonly used animal model for cardiovascular chronic rejection studies is the heterotopic heart transplant model performed in laboratory rodents. This model is used widely in experiments since Ono and Lindsey (3) published their technique. To analyze the findings in the blood vessels, the heart has to be sectioned and all vessels have to be measured.
Another method to investigate chronic rejection in cardiovascular questionings is the aortic transplant model (1, 2). In the orthotopic aortic transplant model, the aorta can easily be histologically evaluated (2). The PVG-to-ACI model is especially useful for CAV studies, since acute vascular rejection is not a major confounding factor and Cyclosporin A (CsA) treatment does not prevent the development of CAV, similar to what we find in the clinical setting (4). A7-day period of CsA is required in this model to prevent acute rejection and to achieve long-term survival with the development of TVP.
This model can also be used to investigate acute cellular rejection and media necrosis in xenogeneic models (5).

This video demonstrates the orthotopic aortic transplant model as a simple model to study the development of transplant vasculopathy (TVP) in rats.

Orthotopic 대동맥 이식 : 만성 Vasculopathy의 개발 연구에 생쥐 모델

Research models of chronic rejection are essential to investigate pathobiological and pathophysiological processes during the development of transplant ...

연구

의학

Longitudinal Evaluation of Mouse Hind Limb Bone Loss After Spinal Cord Injury using Novel, in vivo, Methodology

Spinal cord injury (SCI) is often accompanied by osteoporosis in the sublesional regions of the pelvis and lower extremities, leading to a higher frequency of fractures 1. As these fractures often occur in regions that have lost normal sensory function, the patient is at a greater risk of fracture-dependent pathologies, including death. SCI-dependent loss in both bone mineral density (BMD, grams/cm2) and bone mineral content (BMC, grams) has been attributed to mechanical disuse 2, aberrant neuronal signaling 3 and hormonal changes 4. The use of rodent models of SCI-induced osteoporosis can provide invaluable information regarding the mechanisms underlying the development of osteoporosis following SCI as well as a test environment for the generation of new therapies 5-7 (and reviewed in 8). Mouse models of SCI are of great interest as they permit a reductionist approach to mechanism-based assessment through the use of null and transgenic mice. While such models have provided important data, there is still a need for minimally-invasive, reliable, reproducible, and quantifiable methods in determining the extent of bone loss following SCI, particularly over time and within the same cohort of experimental animals, to improve diagnosis, treatment methods, and/or prevention of SCI-induced osteoporosis.
An ideal method for measuring bone density in rodents would allow multiple, sequential (over time) exposures to low-levels of X-ray radiation. This study describes the use of a new whole-animal scanner, the IVIS Lumina XR (Caliper Instruments) that can be used to provide low-energy (1-3 milligray (mGy)) high-resolution, high-magnification X-ray images of mouse hind limb bones over time following SCI. Significant bone density loss was seen in the tibiae of mice by 10 days post-spinal transection when compared to uninjured, age-matched control (na&iuml;ve) mice (13% decrease, p&lt;0.0005). Loss of bone density in the distal femur was also detectable by day 10 post-SCI, while a loss of density in the proximal femur was not detectable until 40 days post injury (7% decrease, p&lt;0.05). SCI-dependent loss of mouse femur density was confirmed post-mortem through the use of Dual-energy X-ray Absorptiometry (DXA), the current "gold standard" for bone density measurements. We detect a 12% loss of BMC in the femurs of mice at 40 days post-SCI using the IVIS Lumina XR. This compares favorably with a previously reported BMC loss of 13.5% by Picard and colleagues who used DXA analysis on mouse femurs post-mortem 30 days post-SCI 9. Our results suggest that the IVIS Lumina XR provides a novel, high-resolution/high-magnification method for performing long-term, longitudinal measurements of hind limb bone density in the mouse following SCI.

Longitudinal Evaluation of Mouse Hind Limb Bone Loss After Spinal Cord Injury using Novel, in vivo, Methodology

A longitudinal examination of bone loss in the femurs and tibiae of adult mice was performed following spinal cord injury using sequential low-dose X-ray scans. Tibia bone loss was detected throughout the study, while bone loss in the femur was not detected until 40 days post injury.

소설을 사용하여 척수 상해 후에 마우스 뒷다리 뼈 손실의 세로 평가, 생체내에 방법론

Spinal cord injury (SCI) is often accompanied by osteoporosis in the sublesional regions of the pelvis and lower extremities, leading to a higher ...

Orthotopic Small Bowel Transplantation in Rats

Small bowel transplantation has become an accepted clinical option for patients with short gut syndrome and failure of parenteral nutrition (irreversible intestinal failure). In specialized centers improved operative and managing strategies have led to excellent short- and intermediate term patient and graft survival while providing high quality of life 1,3. Unlike in the more common transplantation of other solid organs (i.e. heart, liver) many underlying mechanisms of graft function and immunologic alterations induced by intestinal transplantation are not entirely known6,7. Episodes of acute rejection, sepsis and chronic graft failure are the main obstacles still contributing to less favorable long term outcome and hindering a more widespread employment of the procedure despite a growing number of patients on home parenteral nutrition who would potentially benefit from such a transplant. The small intestine contains a large number of passenger leucocytes commonly referred to as part of the gut associated lymphoid system (GALT) this being part of the reason for the high immunogenity of the intestinal graft. The presence and close proximity of many commensals and pathogens in the gut explains the severity of sepsis episodes once graft mucosal integrity is compromised (for example by rejection). To advance the field of intestinal- and multiorgan transplantation more data generated from reliable and feasible animal models is needed. The model provided herein combines both reliability and feasibility once established in a standardized manner and can provide valuable insight in the underlying complex molecular, cellular and functional mechanisms that are triggered by intestinal transplantation. We have successfully used and refined the described procedure over more than 5 years in our laboratory 8-11. The JoVE video-based format is especially useful to demonstrate the complex procedure and avoid initial pitfalls for groups planning to establish an orthotopic rodent model investigating intestinal transplantation.

Small bowel transplantation has become an accepted treatment option for patients with irreversible intestinal failure. Our experimental model of orthotopic small bowel transplantation in rats serves as a reliable tool to address underlying immunologic and inflammatory processes that complicate intestinal transplantation.

쥐 Orthotopic 작은 창자 이식

Small  bowel transplantation has become an accepted clinical option for patients with  short gut syndrome and failure of parenteral nutrition ...

Orthotopic Liver Transplantation in Rats

Clinical progress in the field of liver transplantation has been largely supported by animal models1,2. Since the publication of the first orthotopic rat liver transplantation in 1979 by Kamada et al.3, this model has remained the gold standard despite various proposed alternative techniques4. Nevertheless, its broader use is limited by its steep learning curve5.
In this video paper, we show a simple and easy-to-establish revision of Kamada's two-cuff technique. The suprahepatic vena cava anastomosis is performed manually with a running suture, and the vena porta and infrahepatic vena cava anastomoses are performed utilizing a quick-linker cuff system6. Manufacturing the quick-linker kit is shown in a separate video paper.

We present an easy-to-establish revision of the classical two-cuff technique for orthotopic liver transplantation in rat.

쥐에게 Orthotopic 간 이식

Clinical progress in the field of liver transplantation has been largely supported by animal models1,2. Since the publication of the first orthotopic rat ...

Orthotopic Aortic Transplantation in Mice for the Study of Vascular Disease

Vascular procedures involving anastomoses in the mouse are generally thought to be difficult and highly dependent on the skill of the individual surgeon. This is largely true, but there are a number of important principles that can reduce the difficulty of these procedures and enhance reproducibility. Orthotopic aortic transplantation is an excellent procedure in which to learn these principles because it involves only two end-to-end anastomoses, but requires good suturing technique and handling of the vessels for consistent success. This procedure begins with the procurement of a length of abdominal aorta from a donor animal, followed by division of the native aorta in the recipient. The procured aorta is then placed between the divided ends of the recipient aorta and sutured into place using end-to-end anastomoses. To accomplish this objective successfully requires a high degree of concentration, good tools, a steady hand, and an appreciation of how easily the vasculature of a mouse can be damaged, resulting in thrombosis. Learning these important principles is what occupies most of the beginner's time when learning microsurgery in small rodents. Throughout this protocol, we refer to these important points. This model can be used to study vascular disease in a variety of different experimental systems1-8. In the context shown here, it is most often used for the study of post-transplant vascular disease, a common long-term complication of solid organ transplantation in which intimal hyperplasia occurs within the allograft. The primary advantage of the model is that it facilitates quantitative morphometric analyses and the transplanted vessel lies contiguous to the endogenous vessel, which can serve as an additional control9. The technique shown here is most often used for mice weighing 18-25 grams. We have accumulated most of our experience using the C57BL/6J, BALB/cJ, and C3H/HeJ strains.

We describe a technique in which a section of the abdominal aorta from a mouse is transplanted orthotopically to just below the renal arteries in an allogeneic or syngeneic recipient. This technique can be useful in studies in which transplantation of large arteries of uniform size is deemed advantageous.

혈관 질병의 연구에 대한 마우스의 Orthotopic 대동맥 이식

Vascular procedures involving anastomoses in the mouse are generally thought to be difficult and highly dependent on the skill of the individual surgeon. ...

A Modified Heterotopic Swine Hind Limb Transplant Model for Translational Vascularized Composite Allotransplantation (VCA) Research

Vascularized Composite Allotransplantation (VCA) such as hand and face transplants represent a viable treatment option for complex musculoskeletal trauma and devastating tissue loss. Despite favorable and highly encouraging early and intermediate functional outcomes, rejection of the highly immunogenic skin component of a VCA and potential adverse effects of chronic multi-drug immunosuppression continue to hamper widespread clinical application of VCA. Therefore, research in this novel field needs to focus on translational studies related to unique immunologic features of VCA and to develop novel immunomodulatory strategies for immunomodulation and tolerance induction following VCA without the need for long term immunosuppression.
This article describes a reliable and reproducible translational large animal model of VCA that is comprised of an osteomyocutaneous flap in a MHC-defined swine heterotopic hind limb allotransplantation. Briefly, a well-vascularized skin paddle is identified in the anteromedial thigh region using near infrared laser angiography. The underlying muscles, knee joint, distal femur, and proximal tibia are harvested on a femoral vascular pedicle. This allograft can be considered both a VCA and a vascularized bone marrow transplant with its unique immune privileged features. The graft is transplanted to a subcutaneous abdominal pocket in the recipient animal with a skin component exteriorized to the dorsolateral region for immune monitoring.
Three surgical teams work simultaneously in a well-coordinated manner to reduce anesthesia and ischemia times, thereby improving efficiency of this model and reducing potential confounders in experimental protocols. This model serves as the groundwork for future therapeutic strategies aimed at reducing and potentially eliminating the need for chronic multi-drug immunosuppression in VCA.

A Modified Heterotopic Swine Hind Limb Transplant Model for Translational Vascularized Composite Allotransplantation VCA Research

Vascularized Composite Allotransplantations (VCA) have become a clinical reality. However, broad clinical application of VCA is limited by chronic multi-drug immunosuppression. The authors present a reliable and reproducible large animal model to translate novel immunomodulatory strategies that can minimize or potentially eliminate the need of immunosuppression in VCA.

번역 상 혈관을 조성한 복합 동종 이식 (VCA) 연구를위한 수정 된 이소성 돼지 뒷다리 이식 모델

Vascularized Composite Allotransplantation (VCA) such as hand and face transplants represent a viable treatment option for complex musculoskeletal trauma ...

Mouse Kidney Transplantation: Models of Allograft Rejection

Rejection of the transplanted kidney in humans is still a major cause of morbidity and mortality. The mouse model of renal transplantation closely replicates both the technical and pathological processes that occur in human renal transplantation. Although mouse models of allogeneic rejection in organs other than the kidney exist, and are more technically feasible, there is evidence that different organs elicit disparate rejection modes and dynamics, for instance the time course of rejection in cardiac and renal allograft differs significantly in certain strain combinations. This model is an attractive tool for many reasons despite its technical challenges. As inbred mouse strain haplotypes are well characterized it is possible to choose donor and recipient combinations to model acute allograft rejection by transplanting across MHC class I and II loci. Conversely by transplanting between strains with similar haplotypes a chronic process can be elicited were the allograft kidney develops interstitial fibrosis and tubular atrophy. We have modified the surgical technique to reduce operating time and improve ease of surgery, however a learning curve still needs to be overcome in order to faithfully replicate the model. This study will provide key points in the surgical procedure and aid the process of establishing this technique.

Here, we present a protocol to study the immunology of rejection. The surgical model presented reports a short operating time and a concise technique. Depending on the donor-recipient strain combination, the transplanted kidney may develop acute cellular rejection or chronic allograft damage, defined by interstitial fibrosis and tubular atrophy.

마우스 신장 이식 : 동종 이식 거부의 모델

Rejection of the transplanted kidney in humans is still a major cause of morbidity and mortality. The mouse model of renal transplantation closely ...

A "Patient-Like" Orthotopic Syngeneic Mouse Model of Hepatocellular Carcinoma Metastasis

The majority of cancer-related deaths are caused by the metastasis of the cancer rather than the primary tumor itself. Yet, the underlying mechanisms of cancer metastasis are still unclear. Animal models are essential for elucidating the mechanisms and for evaluating novel strategies for the treatment of metastatic cancers. Here, an in-depth description of a &#8220;patient-like&#8221; orthotopic syngeneic mouse model for exploring the mechanisms of metastasis of solid organ tumors is provided. The survival surgical implantation of BNL 1ME A.7R.1 mouse hepatocellular carcinoma cells directly into the liver (the organ of origin) of the inbred wild-type immune competent laboratory mouse strain, BALB/c is described. The success and reproducibility of this methodology recommends it for widespread use in elucidating the biological mechanisms of solid organ cancer metastasis.

The metastatic spread of cancer is the major cause of cancer-related deaths. We provide an in-depth description of our survival surgery methodology for establishing a &#8220;patient-like&#8221; orthotopic syngeneic mouse model system for studying the mechanisms of metastasis in solid organ tumors.

&quot;환자와 같은&quot;동소 이식 동계 마우스 모델 간세포 암의 전이

The majority of cancer-related deaths are caused by the metastasis of the cancer rather than the primary tumor itself. Yet, the underlying mechanisms of ...

Preclinical Model of Hind Limb Ischemia in Diabetic Rabbits

Peripheral vascular disease is a widespread clinical problem that affects millions of patients worldwide. A major consequence of peripheral vascular disease is the development of ischemia. In severe cases, patients can develop critical limb ischemia in which they experience constant pain and an increased risk of limb amputation. Current therapies for peripheral ischemia include bypass surgery or percutaneous interventions such as angioplasty with stenting or atherectomy to restore blood flow. However, these treatments often fail to the continued progression of vascular disease or restenosis or are contraindicated due to the overall poor health of the patient. A promising potential approach to treat peripheral ischemia involves the induction of therapeutic neovascularization to allow the patient to develop collateral vasculature. This newly formed network alleviates peripheral ischemia by restoring perfusion to the affected area. The most frequently employed preclinical model for peripheral ischemia utilizes the creation of hind limb ischemia in healthy rabbits through femoral artery ligation. In the past, however, there has been a strong disconnect between the success of preclinical studies and the failure of clinical trials regarding treatments for peripheral ischemia. Healthy animals typically have robust vascular regeneration in response to surgically induced ischemia, in contrast to the reduced vascularity and regeneration in patients with chronic peripheral ischemia. Here, we describe an optimized animal model for peripheral ischemia in rabbits that includes hyperlipidemia and diabetes. This model has reduced collateral formation and blood pressure recovery in comparison to a model with a higher cholesterol diet. Thus, the model may provide better correlation with human patients with compromised angiogenesis from the common co-morbidities that accompany peripheral vascular disease.

We describe a surgical procedure used to induce peripheral ischemia in rabbits with hyperlipidemia and diabetes. This surgery acts as a preclinical model for conditions experienced in peripheral artery disease in patients. Angiography is also described as a means to measure the extent of introduced ischemia and recovery of perfusion.

당뇨병 토끼에서의 뒷 사지의 전 임상 모델

Peripheral vascular disease is a widespread clinical problem that affects millions of patients worldwide. A major consequence of peripheral vascular ...

A Pre-Clinical Porcine Model of Orthotopic Heart Transplantation

Fifty-years following the first successful report, cardiac transplantation remains the gold-standard treatment for eligible patients with advanced heart failure. Multiple small-animal models of heart transplantation have been used to study the acute and long-term effects of novel therapies. However, few are tested and demonstrated success in clinical trials. It is of critical importance to evaluate new therapies in a clinically relevant large-animal model for efficient and reliable translation of basic studies&#39;&#160;findings. Here, we describe a pre-clinical large-animal (porcine) model of orthotopic heart transplantation that has been firmly established and previously used to investigate novel cardioprotective strategies. This procedure focuses on acute ischemia-reperfusion injury and is a reliable method to investigate novel interventions which have been tested and validated in smaller experimental models, such as the murine model. We demonstrate its usefulness in assessing cardiac performance during the early post-transplantation period and other potential possibilities enabled by the model.

Here, we describe a pre-clinical large-animal (porcine) model of orthotopic heart transplantation that has been firmly established and utilized to investigate novel cardioprotective strategies.

정형외 심장 이식의 전 임상 돼지 모델

Fifty-years following the first successful report, cardiac transplantation remains the gold-standard treatment for eligible patients with advanced heart ...