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Biomolecules
Volume 12
Issue 5
10.3390/biom12050698
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Article
Peer-Review Record

Extracellular Vesicles from Steatotic Hepatocytes Provoke Pro-Fibrotic Responses in Cultured Stellate Cells

Biomolecules 2022, 12(5), 698; https://doi.org/10.3390/biom12050698
by Maria Teresa Koenen 1,2,†, Elisa Fabiana Brandt 1, Dawid Marcin Kaczor 2, Tim Caspers 1, Alexandra Catharina Anna Heinzmann 2, Petra Fischer 1, Daniel Heinrichs 1, Theresa Hildegard Wirtz 1, Christian Trautwein 1, Rory R Koenen 2,* and Marie-Luise Berres 1,*
Reviewer 1:
Yong Joo Park
Reviewer 2: Anonymous
Biomolecules 2022, 12(5), 698; https://doi.org/10.3390/biom12050698
Submission received: 5 April 2022 / Revised: 6 May 2022 / Accepted: 10 May 2022 / Published: 13 May 2022
(This article belongs to the Special Issue Recent Advances in Cellular and Molecular Mechanisms of Cardiovascular and Metabolic Diseases)

Round 1

Reviewer 1 Report

This study showed that extracellular vesicles from steatotic hepatocytes provoke pro-fibrotic responses in hepatic stellate cells (HSCs). This manuscript was interesting, well-written and used appropriate methods. I have minor questions before publication.

  1. Author used primary HSCs only for migration, not for evaluating pro-fibrotic responses. Is there any reason for it?
  2. I suggest analyzing the contents in extracellular vesicles to figure out the causative growth factors or cytokines which can increase the pro-fibrotic responses.

Author Response

Please see attached file with our response to reviewer 1.

Author Response File: Author Response.pdf

Reviewer 2 Report

This is an interesting paper tried to address pro-fibrotic response of EV from steatotic hepatocytes on  cultured stellate cells. Overall, it is an imprtant topic for the field if the proper mechanistic approach is provided:

1- The EV induced phenotype change was described well but there is no mechanism on pro-fibrotic effect. Why EV induce profibrotic effect? how? Is it related on the secretome of the cells after EV treatment? This is something that the author needs to address it. 

2- Detection of pro-fibrotic effect was in-complete. The respected author should determine the secreted collagen and fibronectin using WB. 

3- The mechanism of proliferation should be determined. 

Technical Correction:

1- The cell number in 96 well plate is too high and could potentially induce significant error in MTT assay.

2- All information regarding the antibodies should be provided. 

3- n=3 of whole data should be provided as supplementary figures. 

Author Response

Please see attached file with our response to reviewer 2.

Author Response File: Author Response.pdf

Round 2

Reviewer 2 Report

Although the respected authors were not able to answer some of my suggestions (1, 3 comments) with experimental approach, their answers and changes of the tone in the manuscript were very good. The current paper will open several opportunities for future investigations as explained by respected authors. 

Author Response

Thanks.

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