Pan Jun, Yan Sheng, Gao Jun-Jie, Wang Ying-Ying, Lu Zhong-Jie, Cui Chen-Wei, Zhang Yao-Hui, Wang Yan, Meng Xue-Qin, Zhou Lin, Xie Hai-Yang, Zheng Jessica, Zheng Ming H, Zheng Shu-Sen
Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China.
Centre for Orthopaedic Research, School of Surgery, University of Western Australia, Western Australia 6009, Australia.
Int J Biochem Cell Biol. 2016 Nov;80:124-131. doi: 10.1016/j.biocel.2016.10.003. Epub 2016 Oct 5.
Organ decellularization is emerging as a promising regenerative medicine approach as it is able to provide an acellular, three-dimensional biological scaffold material that can be seeded with living cells for organ reengineering. However this application is currently limited to donor-derived decellularized organs for reengineering in vitro and no study has been conducted for re-engineering the decellularized organ in vivo. We developed a novel technique of a single liver lobe decellularization in vivo in live animals. Using a surgical method to generate a by-pass circulation through the portal vein and infra-hepatic vena cava with a perfusion chamber system, we decellularized the single liver lobe and recellularized it with allogenic primary hepatocytes. Our results showed that the decellularization process in vivo can preserve the vascular structural network and functional characteristics of the native liver lobe. It allows for efficient recellularization of the decellularized liver lobe matrix with allogenic primary hepatocytes. Upon the re-establishment of blood circulation, the recellularized liver lobe is able to gain the function and the allogenic hepatocytes are able to secret albumin. Our findings provide a proof of principle for the in vivo reengineering of liver.
器官去细胞化作为一种很有前景的再生医学方法正在兴起,因为它能够提供一种无细胞的三维生物支架材料,可接种活细胞用于器官再造。然而,目前这种应用仅限于供体来源的去细胞化器官用于体外再造,尚未有在体内对去细胞化器官进行再造的研究。我们开发了一种在活体动物体内对单个肝叶进行去细胞化的新技术。通过手术方法利用灌注腔系统在门静脉和肝下腔静脉之间建立旁路循环,我们对单个肝叶进行了去细胞化处理,并用同种异体原代肝细胞重新细胞化。我们的结果表明,体内去细胞化过程可以保留天然肝叶的血管结构网络和功能特性。它允许用同种异体原代肝细胞有效地对去细胞化肝叶基质进行重新细胞化。在重新建立血液循环后,重新细胞化的肝叶能够恢复功能,同种异体肝细胞能够分泌白蛋白。我们的研究结果为肝脏的体内再造提供了原理证明。