Dear Authors,

Mesenchymal stem cell transplantation is very valid and novel approach in treating endometrial pathologies. There is no clear understanding of etiologies of endometrial pathologies e.g. endometriois in humans. Your manuscript highlights the positive effect of multiple tranaplantations of human UC-MSCs with possible mechanistic insights e.g. angiogenesis, releasing anti-inflamatory factors and anti-fibrosis factors. However, manuscript lacks little bit of consistancy and clear methodology followed for transplantations. Please go through bellow mentioned comments in detail:–

Comments on abstract, title, references

Abstract

Is the aim clear? – Yes, very clear aim.

Is it clear what the study found and how they did it? –Yes

Title

Is the title informative and relevant? – Yes!

References

Are the references:

Relevant? – Yes Recent? – Yes Referenced correctly? –Yes Are appropriate key studies included? – Yes

Comments on introduction/background

Is it clear what is already known about this topic? –Yes! ● Is the research question clearly outlined? –Yes! ● Is the research question justified given what is already known about the topic? –Yes!

Comments on methodology

Is the process of subject selection clear? –Yes. ● Are the variables defined and measured appropriately? –Yes ● Are the study methods valid and reliable?

Methodology is clearly defined and results well analyzed. However, at one place authors mention MSCs were transplanted into each uterus but at every other place transplantations were shown to be carried out through tail vein. This discrepancy should have been clarified.

● Is there enough detail in order to replicate the study? –Yes

Comments on data and results

Is the data presented in an appropriate way? –Yes, but figures are not clear and have room to improve. Statistics: Lack of sample size indication is a major handicap. Therefore, I am not sure if ANOVA was the best test without information about normal distribution of data.

● Tables and figures relevant and clearly presented? –Figure 1 lacks clarity and does not stand on its own. It does not have sample size. Font is not clear and readable. Rest of the figures differ bit in nomenclature and lack consistency. (UC-MSC group is referred sometimes as MSC group, authors could have stick to one).

Figures: Overall, they have room to be improved. Not only their size and consistency, but also the immunostainings have very low resolution that may allow to any conclusion. What about the IHC for cytokeratin? Co-localization of KI67 with human antigen is important and should be moved as a main figure.Are MSC colonizing endometrium? Are they proliferative? Is there any rejection of human cells in non-immunodefficient rats? Too many questions that are not adressed at any point of the manuscript.

● Appropriate units, rounding, and number of decimals? –Yes ● Titles, columns, and rows labelled correctly and clearly? –Yes ● Categories grouped appropriately? –Yes ● Does the text in the results add to the data or is it repetitive? –Yes, it does add and not repetitive ● Are you clear about what is a statistically significant result? –Yes ● Are you clear about what is a practically meaningful result? –Yes

Comments on discussion and conclusions

Are the results discussed from multiple angles and placed into context without being overinterpreted? –Yes, article touches the overall usefulness while sticking within the boundaries of their results.

● Do the conclusions answer the aims of the study? –Yes

● Are the conclusions supported by references or results? –Yes

● Are the limitations of the study fatal or are they opportunities to inform future research? –Article does not talk about limitations of the study

However, looking at overall discussion part whhich is poor and some results, especially those regarding the antiinflamatory effect of MSCs are overinterpreted if one only refers to the data provided by the manuscript. May probably ibuprofen (antiinflamatory) have the same effect that MSC transplantation? This is an interesting experiment that is not even commented in the discussion.

Overall statement or summary of the article and its findings in your own words

Article is well written and addresses the issue of female infertility. However, figures lack bit of clarity and are not stand alone. Discussion doens not start with the main outcome or result but it talks about why they chose UC-MSCs. Authors discuss about their results but somewhere in the middle. So, discussion could be restructured accordingly.

Overall strengths of the article and what impact it might have in your field

Article supports the conclusions with different angles and using several methodologies. It would certenly promote the preclinical research on MSCs for treatment of infertility.

Specific comments on weaknesses of the article and what could be done to improve it

Major points in the article which needs clarification, refinement, reanalysis, rewrites and/or additional information and suggestions for what could be done to improve the article.

1. Methodology regarding transplantations needs more clarification.
2. Figures needs to be improved to stand on themselves (e.g. sample size needs to be mentioned).
3. Rewrite and restructure of discussion would be needed.
4. Limitations of the study needs to be incorporated which is missing from current published version.
5. Authos should discuss how these preclinical results could be translated in humans and what could be the limitations.

Minor points like figures/tables not being mentioned in the text, a missing reference, typos, and other inconsistencies.

1. Article lacks consistancy in abbreviations used: same group is termed as UC-MSCs or MSCs some times.
2. In Table 1, all gene names start with "rat", which I find repetitive.

Comments to Editor,

Dear Editor,

Article suggests novel method of multile UC-MSCs transplantations with very promising results. However, it could be further improved regarding quality of figures and clarity of methodology. I find manuscript acceptable for publication with minor modifications.

Thank you!