Title: Hepatic recruitment of myeloid-derived suppressor cells upon liver injury promotes both
liver regeneration and fibrosis
Version: 1 Date: 09 Jun 2023
Reviewer's report:
Qiongwen and colleagues have studied the recruitment of MDSCs to the liver during ongoing
injury. They also assessed the effect of this recruitment on liver regeneration and fibrosis. The
rationale behind the study is well explained and it is an interesting topic. However, there are
several points that need to be addressed to fully concluded on the experiment performed by the
authors.
Major comments:
1. Figure 1A: The H&E seems saturated and the image blurry. Could the authors provide clearer
pictures?
2. Figure 1B: is the percentage of MDSCs on total liver cells or on total immune cells? This
should be specified. Moreover, at which time point is the control analysed?
3. Controls are missing in this study. A control should be provided for each time point for all
the panels in figure 1 and 2, and figure 3B. It is not possible to conclude on the effect of the
different models on MDSCs recruitment if a time matched post injection control is not provided
for each time point.
4. Figure 4C: The authors state that the cells growing out of the liver pieces are hepatocytes. To
be able to conclude this, the authors should provide a staining or a flow cytometry analysis of
these cells with a hepatocyte marker, such as HFN4a for example.
5. Figure 4F: Which maker was used to stain for hepatocytes? It is not indicated in the text
neither in the M&M. To state that hepatocytes were the cells with increased G2/M phase, the
authors need to gate on hepatocyte marker-positive cells. If not, the proliferation could be due
to other cell types.
6. Figure 4G: how can the authors state that the cells growing out of the liver pieces are
hepatocytes if most of them are CK18 negative? Moreover, if the authors see more a-SMA,
which can correlate with liver fibrosis to some extent, it means that some of the proliferative
cells are not hepatocytes but HSC. The authors should revise their statement.
7. Figure 5C: it is puzzling that all the antibodies had similar effects. It means that the full cocktail
of these cytokines is needed to induce the hepatocytes proliferation and that no compensatory
mechanisms exist when one of the cytokines is lost. The authors should discuss this.
Minor comments:
1. Throughout the text, spaces are missing between two words, punctuations are in the wrong
places, and capital letter appear in the middle of a sentence. This should be check thoroughly.
2. The end of the first paragraph of the introduction ends with “extracellular matrix (ECM), ,
and [3-6].” The “, , and” should be removed.
3. The authors need to indicate in the M&M section on the co-culture experiment how they
assessed the growth of liver tissue, although details will be provided in a different section.
4. Overall, the English will need some proofing to increase the readability of the manuscript.
5. In the conclusion, the authors state that TGFb is a pro-inflammatory cytokine. I believe this
is a mistake.
Title: Hepatic recruitment of myeloid-derived suppressor cells upon liver injury promotes both
liver regeneration and fibrosis
Version: 1 Date: 09 Jun 2023
Reviewer's report:
Qiongwen and colleagues have studied the recruitment of MDSCs to the liver during ongoing
injury. They also assessed the effect of this recruitment on liver regeneration and fibrosis. The
rationale behind the study is well explained and it is an interesting topic. However, there are
several points that need to be addressed to fully concluded on the experiment performed by the
authors.
Major comments:
1. Figure 1A: The H&E seems saturated and the image blurry. Could the authors provide clearer
pictures?
2. Figure 1B: is the percentage of MDSCs on total liver cells or on total immune cells? This
should be specified. Moreover, at which time point is the control analysed?
3. Controls are missing in this study. A control should be provided for each time point for all
the panels in figure 1 and 2, and figure 3B. It is not possible to conclude on the effect of the
different models on MDSCs recruitment if a time matched post injection control is not provided
for each time point.
4. Figure 4C: The authors state that the cells growing out of the liver pieces are hepatocytes. To
be able to conclude this, the authors should provide a staining or a flow cytometry analysis of
these cells with a hepatocyte marker, such as HFN4a for example.
5. Figure 4F: Which maker was used to stain for hepatocytes? It is not indicated in the text
neither in the M&M. To state that hepatocytes were the cells with increased G2/M phase, the
authors need to gate on hepatocyte marker-positive cells. If not, the proliferation could be due
to other cell types.
6. Figure 4G: how can the authors state that the cells growing out of the liver pieces are
hepatocytes if most of them are CK18 negative? Moreover, if the authors see more a-SMA,
which can correlate with liver fibrosis to some extent, it means that some of the proliferative
cells are not hepatocytes but HSC. The authors should revise their statement.
7. Figure 5C: it is puzzling that all the antibodies had similar effects. It means that the full cocktail
of these cytokines is needed to induce the hepatocytes proliferation and that no compensatory
mechanisms exist when one of the cytokines is lost. The authors should discuss this.
Minor comments:
1. Throughout the text, spaces are missing between two words, punctuations are in the wrong
places, and capital letter appear in the middle of a sentence. This should be check thoroughly.
2. The end of the first paragraph of the introduction ends with “extracellular matrix (ECM), ,
and [3-6].” The “, , and” should be removed.
3. The authors need to indicate in the M&M section on the co-culture experiment how they
assessed the growth of liver tissue, although details will be provided in a different section.
4. Overall, the English will need some proofing to increase the readability of the manuscript.
5. In the conclusion, the authors state that TGFb is a pro-inflammatory cytokine. I believe this
is a mistake.
Please review this paper.
user
Title: Hepatic recruitment of myeloid-derived suppressor cells upon liver injury promotes both
liver regeneration and fibrosis
Version: 1 Date: 09 Jun 2023
Reviewer's report:
Qiongwen and colleagues have studied the recruitment of MDSCs to the liver during ongoing
injury. They also assessed the effect of this recruitment on liver regeneration and fibrosis. The
rationale behind the study is well explained and it is an interesting topic. However, there are
several points that need to be addressed to fully concluded on the experiment performed by the
authors.
Major comments:
1. Figure 1A: The H&E seems saturated and the image blurry. Could the authors provide clearer
pictures?
2. Figure 1B: is the percentage of MDSCs on total liver cells or on total immune cells? This
should be specified. Moreover, at which time point is the control analysed?
3. Controls are missing in this study. A control should be provided for each time point for all
the panels in figure 1 and 2, and figure 3B. It is not possible to conclude on the effect of the
different models on MDSCs recruitment if a time matched post injection control is not provided
for each time point.
4. Figure 4C: The authors state that the cells growing out of the liver pieces are hepatocytes. To
be able to conclude this, the authors should provide a staining or a flow cytometry analysis of
these cells with a hepatocyte marker, such as HFN4a for example.
5. Figure 4F: Which maker was used to stain for hepatocytes? It is not indicated in the text
neither in the M&M. To state that hepatocytes were the cells with increased G2/M phase, the
authors need to gate on hepatocyte marker-positive cells. If not, the proliferation could be due
to other cell types.
6. Figure 4G: how can the authors state that the cells growing out of the liver pieces are
hepatocytes if most of them are CK18 negative? Moreover, if the authors see more a-SMA,
which can correlate with liver fibrosis to some extent, it means that some of the proliferative
cells are not hepatocytes but HSC. The authors should revise their statement.
7. Figure 5C: it is puzzling that all the antibodies had similar effects. It means that the full cocktail
of these cytokines is needed to induce the hepatocytes proliferation and that no compensatory
mechanisms exist when one of the cytokines is lost. The authors should discuss this.
Minor comments:
1. Throughout the text, spaces are missing between two words, punctuations are in the wrong
places, and capital letter appear in the middle of a sentence. This should be check thoroughly.
2. The end of the first paragraph of the introduction ends with “extracellular matrix (ECM), ,
and [3-6].” The “, , and” should be removed.
3. The authors need to indicate in the M&M section on the co-culture experiment how they
assessed the growth of liver tissue, although details will be provided in a different section.
4. Overall, the English will need some proofing to increase the readability of the manuscript.
5. In the conclusion, the authors state that TGFb is a pro-inflammatory cytokine. I believe this
is a mistake.
assistant