-->PONE-D-25-45087-->-->Effects of intermittent hypoxia on adipose-derived mesenchymal stem cells in protecting alveolar type II cells from injury-->-->PLOS ONE

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PLOS ONE

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Reviewer #1: Yes

Reviewer #2: Partly

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Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

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-->5. Review Comments to the Author

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Reviewer #1: This study addresses an important question. The methods and results are clearly described. I have the following suggestions for the current manuscript.

The hypoxia protocols are not fully specified. For full reproducibility, please state ramp time to each O₂ setpoint. A brief note on how O₂ was monitored would be better.

Your data show similar anti-apoptotic and anti-oxidative effects for IH and 24SH. IH also shows lower VEGF and stronger GSH recovery. However, causal tests are not included. Emphasize correlation rather than superiority and add an appropriate discussion of this point in the Discussion section.

In Results 3.4, flow cytometry indicates reduced apoptosis across all CM groups, while western blots show no significant improvement with NO or 12SH. Please confirm matched assay timepoints.

In multi-panel figures (e.g., Figure 2), the order is not fully consistent. Please revise either the figure or the text so that the first in-text callouts follow alphabetical order, and update the Figure legend to match the final sequence to optimize readability.

Thank you for considering my feedback!

Reviewer #2: This paper explored the effects of intermittent hypoxic preconditioning on ADSCs. It was found that intermittent hypoxia preconditioning leads to changes in cytokine secretion compared to sustained hypoxia preconditioning. Their therapeutic effects of anti-apoptosis and anti-oxidation remained the same. The topic is interesting. The following comments should be addressed before the paper can be considered for publication

1� In the abstract, the authors mentioned that “intermittent hypoxia preconditioning leads to differences in the secretion of certain cytokines”. The authors should specify which cytokines were involved and indicate whether their levels increased or decreased.

2� In the introduction, the authors should introduce intermittent hypoxia preconditioning and discuss whether this condition has been studied using mesenchymal stem cells.

3� The authors should do some tests to make sure that the isolated ADSCs meet the minimum MSC criteria recommended by ISCT. First, they must adhere to plastic in standard culture conditions. Second, they must express a specific set of surface markers, namely CD105, CD73, and CD90, while lacking markers like CD45, CD34, CD14, CD11b, CD79a, CD19, and HLA-DR. Third, they must be able to differentiate into osteoblasts, adipocytes, and chondrocytes in vitro.

4� The authors should also study the effects of intermittent hypoxia preconditioning on proliferation and stemness of ADSC.

5� The authors should propose some next steps or future studies.

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Reviewer #1: No

Reviewer #2: No

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Effects of intermittent hypoxia on adipose-derived mesenchymal stem cells in protecting alveolar type II cells from injury

PONE-D-25-45087R1

Dear Dr. Li,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

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Kind regards,

Cheng-Maw Ho

Academic Editor

PLOS One

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