Kallenbach Klaus, Leyh Rainer G, Lefik Elena, Walles Thorsten, Wilhelmi Matthias, Cebotari Serghei, Schmiedl Andreas, Haverich Axel, Mertsching Heike
Department of Thoracic and Cardiovascular Surgery, Hennover Medical School, Carl-Neuberg-Strasse 1, 30623 Hannover, Germany.
Biomaterials. 2004 Aug;25(17):3613-20. doi: 10.1016/j.biomaterials.2003.10.040.
For cardiovascular tissue engineering, acellularized scaffolds of porcine matrices have been successfully used. However, the possibility of porcine endogenous retrovirus (PERV) transmission remains debatable. In this study, we investigated whether acellularized porcine vascular scaffolds cause cross-species transmission of PERV in a xenogenic model.
Porcine pulmonary arteries were acellularized and implanted into sheep in orthotopic position (n=6). Cardiopulmonary bypass support was used for all operations. Blood samples were collected regularly up to 6 months after the operation, and cellular components were tested for PERV infection by PCR and RT-PCR. Grafts were explanted 6 and 12 months after implantation. Tissue samples were characterized by histology and electron microscopy and tested for PERV sequences.
All animals survived the procedure and follow up until explantation of the grafts. PERV DNA was detectable in acellularized scaffolds of porcine matrices. Acellular porcine pulmonary arteries scaffolds were repopulated in vivo by autologous cells of the host, leading to a vessel consisting of all cellular components of the vessel wall. No PERV sequences were detectable neither in all tested peripheral blood samples nor in tissue samples of in vivo recellularized grafts up to 6 months after implantation. Electron microscopy revealed no signs of graft infection by retrovirus.
Guided tissue regeneration of acellularized vascular porcine matrix scaffolds leads to structured vessels up to one year without risk of PERV transmisson.
在心血管组织工程中,猪基质的脱细胞支架已成功应用。然而,猪内源性逆转录病毒(PERV)传播的可能性仍存在争议。在本研究中,我们在异种模型中研究了脱细胞猪血管支架是否会导致PERV的跨物种传播。
将猪肺动脉脱细胞并原位植入绵羊体内(n = 6)。所有手术均使用体外循环支持。术后定期采集血样,直至术后6个月,通过PCR和RT-PCR检测细胞成分是否感染PERV。在植入后6个月和12个月取出移植物。对组织样本进行组织学和电子显微镜检查,并检测PERV序列。
所有动物均存活至移植物取出,且随访期内状况良好。在猪基质的脱细胞支架中可检测到PERV DNA。脱细胞猪肺动脉支架在体内被宿主自体细胞重新填充,形成了一个由血管壁所有细胞成分组成的血管。在植入后长达6个月的所有测试外周血样本和体内再细胞化移植物的组织样本中均未检测到PERV序列。电子显微镜检查未发现移植物感染逆转录病毒的迹象。
脱细胞猪血管基质支架的引导组织再生可在长达一年的时间内形成结构完整的血管,且无PERV传播风险。