The authors bring a new methodology of liver cell culture to capture the aspects of the tissue physiology and its interaction in between different types of cells present in the liver. The aim of the study is very clear and the article reaches the proposed goal by the authors, showing how to perform a co-culture system and the issues about this specific technique. The study is very relevant and informative taking in consideration that most of the current in vitro liver models focus only on hepatocytes, while it is well know that the liver presents other types of cells that plays a major role in the tissue. All the references used by the authors are relevant and recent. The authors used the references correct manner using key studies to discuss and support what they found. The introduction brings the importance of creating a multi-cell liver culture model in studies related to the liver cells communication. The research question is clearly outlined on the last paragraph the introduction, and the question is justified properly in a fashion way providing a formidable tool to create multi-cell liver culture models with functions and responses superior than hepatocyte-only models. The method selection was very clear and logical. Despite very basic, the characterization is sufficient to give the reader a positive viewpoint of this interesting method. The methods used are reliable and valid, taking in consideration the approach that was given by the authors. The authors were very cautious in describing this specific technique adequately so that it was possible to be reproduced properly. All the data was presented in an appropriate way. Figures and images are very clear and self-explanatory. Authors took care of using proper unit, numbers and labels. All the figures present proper titles. All the categories of the results are done appropriately. The text is not repetitive and it is very clear to find what the authors mentioned on each segment of the results. The statistics used was suitable for this type of study. The significance was properly mentioned on each figure, and in the section of methods of the article. All the results were meaningful based on the aim of the study. The claims are convincing and the manuscript is almost complete.

Major: The authors suggest that the decreased expression of SE-1 in LSECs may be due to the presence of Kupffer cells and the early exposure to the inflammatory environment. 1.Even though it is clear that the decreased expression is caused by the presence of KC, a better clarification in the discussion is necessary and the authors should address this issue.

Suggestions: As an optional improvement it would be very interesting to see how this cell system works in different metabolic functions of the liver , and not only in regards to the inflammation. It would be very interesting to see different metabolic capacities of the liver in this system, including for example glucose and lipid parameters. As an example, would this system be suitable for different studies such as Fatty Liver disease studies, taking in consideration that disorders related with hepatic fat accumulation are in certain degree co-related with inflammation. Optionally, it would be interest to observe the levels of transaminases in the media to see if there is any changes in hepatocytes damages.

The claims was appropriately discussed in the context of previous literature and results. The importance of a system that captures the tissue physiology was very well pointed, and the results were discussed from multiples angles. The study is very promising and open new opportunities to new and more complex studies in the area.