Improved surgical technique for the establishment of a murine model of aortic transplantation

Sun, Hong; Valdivia, Luis A.; Субботин, Владимир; Aı̈touche, Abdelouahab; Fung, John J.; Starzl, Thomas E.; Rao, Abdul S.

doi:10.1002/(sici)1098-2752(1998)18:6<368::aid-micr5>3.0.co;2-f

Cited by 40 publications

(42 citation statements)

References 7 publications

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“…Mouse models of aortic transplantation provide a number of advantages because mice are very well defined immunogenetically 9,12,13 , and they can be easily manipulated to alter their expression of specific genes, if desired. As noted in the introduction, vascular surgery in the mouse is more difficult than most models because of the size of the vessels.…”

Section: Discussionsupporting

confidence: 84%

“…Throughout this protocol, we refer to these important points. This model can be used to study vascular disease in a variety of different experimental systems [1][2][3][4][5][6][7][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.…”

Section: Introductionmentioning

confidence: 99%

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Orthotopic Aortic Transplantation in Mice for the Study of Vascular Disease

Guo

Agarwal

George

2012

JoVE

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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 endto-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 systems [1][2][3][4][5][6][7][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 control 9 . 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. Video LinkThe video component of this article can be found at http://www.jove.com/video/4338/ Protocol 1. Presurgical Preparation 1. Surgical procedures, no matter how carefully done, result in significant stress. To minimize the effects of such stress and to maximize reserves, animals should be maintained in the vivarium for at least 72 hr before use 10,11 . 2. Surgical tools, gauze, and swabs must be sterile. It is not necessary to use sterile gloves providing only the tips of the instruments touch suture or the operative field. 3. For hemostasis, it is imperative that clamping pressures are the minimum necessary. Damage to the vessel due to excessive pressure or rough handling will cause thrombosis, resulting in hind-leg paralysis, bowel ischemia, and death within 24 hr. We have found that using clamps with a pressure of no more than 2 gm/cm 2 eliminates the problem. These clamps are noted in Table 1. Clamp pressures are indicated in the specifications for clamps made by high quality surgical instrument manufacturers. We have found that inexpensive clamps or disposable clamps universally exe...

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Section: Discussionsupporting

confidence: 84%

Section: Introductionmentioning

confidence: 99%

Orthotopic Aortic Transplantation in Mice for the Study of Vascular Disease

Guo

Agarwal

George

2012

JoVE

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“…Murine aortic transplantation was performed with the use of a modified technique described by Sun et al 9 Briefly, a segment of donor thoracic aorta was anastomosed (end to side) to the infrarenal portion of the recipient aorta with interrupted sutures. The native aorta was ligated between the anastomotic sites.…”

Section: Aortic Transplantationmentioning

confidence: 99%

Stromal Cell–Derived Factor-1 and CXCR4 Interaction Is Critical for Development of Transplant Arteriosclerosis

et al. 2004

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Background-Posttransplant chronic allograft deterioration associated with development of transplant arteriosclerosis (TA) remains an unresolved problem. Recent studies suggest that the smooth muscle cells (SMCs) constituting the neointima are derived from recipient hematopoietic stem cells (HSCs). However, the underlying mechanisms of the process are not yet fully elucidated. Methods and Results-We examined the genes expressed in allografts at different stages of TA development using a mice aortic transplantation model. Genes were analyzed by a differential mRNA display technique. We show that stromal cell-derived factor-1␣ (SDF-1␣) is a critical molecular target for the treatment of TA. During the course of TA, intragraft SDF-1␣ expression was upregulated with time, and the circulating HSCs expressing its counterreceptor CXCR4 increased in the recipients receiving allografts. CXCR4-positive HSCs, derived from transplant recipients, migrated into allografts via microvessels in the adventitia and then toward the luminal side. The HSCs differentiated into SMC-like cells, contributing to the in situ formation of the neointima. In support of a functional role for these molecules, in vivo neutralization of SDF-1␣ inhibited HSC mobilization and significantly attenuated neointimal formation. Conclusions-Interaction between SDF-1␣ and CXCR4 plays a key role in TA development. Blockade of SDF-1␣ may become a new therapeutic modality for TA.

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“…It is for this purpose that we have developed an aortic allotransplantation (AOTx) model of CR in mice in which, for the acceptance of the graft, no immunosuppression is required and in which resultant changes established within 30 days posttransplantation are pathognomonic of CR. 4 Reported herein is the role of blockade of costimulation and the evolution of CR.…”

mentioning

confidence: 99%