Ruoß Marc, Häussling Victor, Schügner Frank, Olde Damink Leon H H, Lee Serene M L, Ge Liming, Ehnert Sabrina, Nussler Andreas K
Department of Traumatology, Siegfried Weller Institute, Eberhard Karls University, 72076 Tübingen, Germany.
Matricel GmbH, 52134 Herzogenrath, Germany.
Bioengineering (Basel). 2018 Oct 16;5(4):86. doi: 10.3390/bioengineering5040086.
Due to pronounced species differences, hepatotoxicity of new drugs often cannot be detected in animal studies. Alternatively, human hepatocytes could be used, but there are some limitations. The cells are not always available on demand or in sufficient amounts, so far there has been only limited success to allow the transport of freshly isolated hepatocytes without massive loss of function or their cultivation for a long time. Since it is well accepted that the cultivation of hepatocytes in 3D is related to an improved function, we here tested the Optimaix-3D Scaffold from Matricel for the transport and cultivation of hepatocytes. After characterization of the scaffold, we shipped cells on the scaffold and/or cultivated them over 10 days. With the evaluation of hepatocyte functions such as urea production, albumin synthesis, and CYP activity, we showed that the metabolic activity of the cells on the scaffold remained nearly constant over the culture time whereas a significant decrease in metabolic activity occurred in 2D cultures. In addition, we demonstrated that significantly fewer cells were lost during transport. In summary, the collagen-based scaffold allows the transport and cultivation of hepatocytes without loss of function over 10 days.
由于明显的物种差异，新药的肝毒性在动物研究中往往无法检测到。另外，可以使用人肝细胞，但存在一些局限性。这些细胞并非总能按需获取或获得足够数量，到目前为止，在不大量丧失功能的情况下运输新鲜分离的肝细胞或长时间培养它们仅取得了有限的成功。由于人们普遍认为在三维空间中培养肝细胞与功能改善有关，我们在此测试了Matricel公司的Optimaix-3D支架用于肝细胞的运输和培养。对支架进行表征后，我们将细胞接种在支架上和/或培养超过10天。通过评估肝细胞功能，如尿素生成、白蛋白合成和细胞色素P450（CYP）活性，我们发现支架上细胞的代谢活性在培养期间几乎保持恒定，而在二维培养中代谢活性显著下降。此外，我们证明运输过程中损失的细胞明显更少。总之，这种基于胶原蛋白的支架能够在10天内实现肝细胞的运输和培养且不丧失功能。
