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通过移植扩增后的原代肝细胞三维生物打印肝脏,使肝衰竭小鼠的肝功能恢复活力。

Revitalizing liver function in mice with liver failure through transplantation of 3D-bioprinted liver with expanded primary hepatocytes.

机构信息

State Key Laboratory of Advanced Medical Materials and Devices, Engineering Research Center of Pulmonary and Critical Care Medicine Technology and Device (Ministry of Education), Tianjin Key Laboratory of Biomedical Materials, Institute of Biomedical Engineering, Tianjin Institutes of Health Science, Chinese Academy of Medical Science and Peking Union Medical College, Tianjin 300192, China.

Center for Reproductive Medicine, Jiangxi Maternal and Child Health Hospital, Jiangxi Branch of National Clinical Research Center for Obstetrics and Gynecology, Nanchang Medical College, Nanchang, China.

出版信息

Sci Adv. 2024 Jun 7;10(23):eado1550. doi: 10.1126/sciadv.ado1550.

DOI:10.1126/sciadv.ado1550
PMID:38848358
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11160470/
Abstract

The utilization of three-dimensional (3D) bioprinting technology to create a transplantable bioartificial liver emerges as a promising remedy for the scarcity of liver donors. This study outlines our strategy for constructing a 3D-bioprinted liver, using in vitro-expanded primary hepatocytes recognized for their safety and enhanced functional robustness as hepatic cell sources for bioartificial liver construction. In addition, we have developed bioink biomaterials with mechanical and rheological properties, as well as printing capabilities, tailored for 3D bioprinting. Upon heterotopic transplantation into the mesentery of tyrosinemia or 90% hepatectomy mice, our 3D-bioprinted liver effectively restored lost liver functions, consequently extending the life span of mice afflicted with liver injuries. Notably, the inclusion of an artificial blood vessel in our 3D-bioprinted liver allowed for biomolecule exchange with host blood vessels, demonstrating, in principle, the rapid integration of the bioartificial liver into the host vascular system. This model underscores the therapeutic potential of transplantation for the treatment of liver failure diseases.

摘要

利用三维(3D)生物打印技术来创建可移植的生物人工肝脏,为解决肝脏供体短缺问题提供了一种有前途的方法。本研究概述了我们构建 3D 生物打印肝脏的策略,使用体外扩增的原代肝细胞作为生物人工肝脏构建的肝细胞来源,因其安全性和增强的功能稳健性而得到认可。此外,我们还开发了具有机械和流变性能以及 3D 生物打印能力的生物墨水生物材料。在将我们的 3D 生物打印肝脏异位移植到酪氨酸血症或 90%肝切除小鼠的肠系膜后,它有效地恢复了失去的肝脏功能,从而延长了患有肝损伤的小鼠的寿命。值得注意的是,我们的 3D 生物打印肝脏中包含人工血管,允许与宿主血管进行生物分子交换,从原则上证明了生物人工肝脏快速融入宿主血管系统。该模型突出了移植治疗肝衰竭疾病的治疗潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22a1/11160470/772fe5b6e45e/sciadv.ado1550-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22a1/11160470/cfb3d01b33d1/sciadv.ado1550-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22a1/11160470/5f2095286846/sciadv.ado1550-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22a1/11160470/7abf6d77796e/sciadv.ado1550-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22a1/11160470/b11e7e7e9e37/sciadv.ado1550-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22a1/11160470/aa0e3202e4aa/sciadv.ado1550-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22a1/11160470/772fe5b6e45e/sciadv.ado1550-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22a1/11160470/cfb3d01b33d1/sciadv.ado1550-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22a1/11160470/5f2095286846/sciadv.ado1550-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22a1/11160470/7abf6d77796e/sciadv.ado1550-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22a1/11160470/b11e7e7e9e37/sciadv.ado1550-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22a1/11160470/aa0e3202e4aa/sciadv.ado1550-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22a1/11160470/772fe5b6e45e/sciadv.ado1550-f6.jpg

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