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Article
Peer-Review Record

XYLT1 Deficiency of Human Mesenchymal Stem Cells: Impact on Osteogenic, Chondrogenic, and Adipogenic Differentiation

Int. J. Mol. Sci. 2025, 26(15), 7363; https://doi.org/10.3390/ijms26157363
by Thanh-Diep Ly 1,†, Vanessa Schmidt 1,†, Matthias Kühle 1, Kai Oliver Böker 2, Bastian Fischer 1, Cornelius Knabbe 1 and Isabel Faust-Hinse 1,*
Reviewer 1: Anonymous
Reviewer 2:
Int. J. Mol. Sci. 2025, 26(15), 7363; https://doi.org/10.3390/ijms26157363
Submission received: 20 June 2025 / Revised: 9 July 2025 / Accepted: 28 July 2025 / Published: 30 July 2025
(This article belongs to the Special Issue Molecular Insight into Bone Diseases)

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The manuscript by Thanh-Diep Ly et al claims that XT-I’s pivotal role in regulating differentiation pathways within the bone marrow niche, influencing cellular functions critical for skeletal health. However, the manuscript couldn’t be accepted. The comments and questions are followed.

  1. My main concern is related to the number of data, the manuscript showed that biological and technical replicates per experiment (n = 2) in all figures. The Mat & Met and figure legends section should be more precise and detailed (n). T To make sure the accurate conclusion, The number of experiments is at least 3 in every group.
  2. Cellular proliferation in Figure2A was detected every 1 hour, why so short? In common, at least 8-12 h. What’s difference of WT1 and WT2?
  3. RUNX2 and COL1A1 aren’t chondrogenic differentiation markers in Figure 3, which is osteogenic differentiation markers.
  4. Author showed so much data, however, I can’t find the main conclusion and significance.

Author Response

Please see attachment

Author Response File: Author Response.docx

Reviewer 2 Report

Comments and Suggestions for Authors

Dear authors,

congratulations for your work.

The manuscript is well written, fluent and has a good scientific impact.

It also has a good technological influence and is constructed according to a rational scientific workflow.

I suggest only minors modifications:

  • Lane 140: typo error.
  • Reduce and summarize M&M and Discussion sections.
  • Change the graph in Figure 1C, respect to the figure1A and 1B
  • Lane 587: not only vital bone cells. There are several cell types derived from hMSC
  • Explain better how did you use the primary cells. Are donors cells used as a POOLED batch?
  • Are this POOL the same for each experiments?
  • There is just one issue with the paragraph title " Diminished XYLT1 expression of hMSCs does not critically impair their differentiation into 729 osteoblasts " and the overall title "XYLT1 deficiency of human mesenchymal stem cells impairs adult bone and cartilage homeostasis”
  • 5. XYLT1-deficient adipogenic differentiated hMSCs possess a diminished leptin expression”. Please insert this aspect in the overall title.

Author Response

Please see attachment

Author Response File: Author Response.docx

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