Effect of Adipose-Derived Mesenchymal Stem Cells (ADMSCs) Application in Achilles-Tendon Injury in an Animal Model

Round 1

Reviewer 1 Report

The researchers in this study investigated the effect of adipose derived mesenchymal stem cells in Achilles-tendon injury animal model and showed positive effect through examining few markers.

The study is well conducted and the manuscript is well written. However, the authors are advised to address the below points before it is recommended for publication.

General points:

1.     Line 16: “established” instead of “stablished”

2.     Line 121: “24.08%, respectively” instead of “24.08 respectively”

3.     Line 129: “11.85%, respectively” instead of “11.85% respectively”

4.     What was the expression of GDF-5 and other markers tested in the below study?

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2928041/pdf/ten.tea.2009.0710.pdf

Author Response

Please see the attachment.

Author Response File: Author Response.docx

Reviewer 2 Report

The manuscript cimb-2010677 report some data from a small but potentially interesting study.

I have several comments:

1.       A scheme showing the layout (including timeline, study groups, interventions, readouts) of the experiments should be added.

2.       The small numbers of animals are justified by the obvious ethical reasons. Still those should be critically discussed as a study limitation.

3.       What are the other limitations of the study?

4.       Figure 2 and corresponding parts of the text. Why only 3 out of 4 ADMSC animals demonstrated SRY positivity?

5.       In continuation, were only SRY-positive 3 animals included in subsequent analyses or all 4 of them? How would the calculations differ depending of inclusion of the fourth, negative animal? The other version should be presented in the supplement.

6.       E.g. “36.62% and 24.08%”. Please, make “36.6% and 24.1%” out of it. And in the similar places.

7.       Figures 3 and 4. Please, why what you show. Means with SD, SEM? Elaborate the legends. Elaborate the names of the groups already in the figure. Especially “TENDON” and “LESION” are unclear.

8.       Table 1. The same. What is given? Median with IQR? Explain abbreviations.

9.       In the Discussion section, please speculate about the potential involvement of MSC-derived EVs in the effects observed by you (PMID: 34067156). Other mechanisms?

10.   Statistics. Was Mann-Whitney U test the only test used? If yes, simplify “Mann-Whitney U test was used for non-parametric data applied to two independent samples.” to “Mann-Whitney U test was used to compare two independent samples.”. Otherwise, it is unclear.

11.   Statistics. In continuation to points 7 and 8. How are the data given in the main text? Mean/median? Add error (SD, SEM, IQR) where needed.

12.   Figure 1 has poor quality.

Author Response

Please see the attachment.

Author Response File: Author Response.docx

Reviewer 3 Report

This is a very thorough experimental technique with a meticulous presentation and analysis of results. Please only change the sequence of presentation, as materials and methods are at the end of the manuscript

Author Response

This is a very thorough experimental technique with a meticulous presentation and analysis of results. Please only change the sequence of presentation, as materials and methods are at the end of the manuscript

——The sequence was corrected as suggested.

Round 2

Reviewer 2 Report

The Authors have addressed my comments very well, except that the new Figure 1 mentioned in the reply has not been added to the manuscript file. Please, amend.

Author Response

Figure 1 was added.