The Role of Mesenchymal Stromal Cells and Their Products in the Treatment of Injured Spinal Cords
Round 1
Reviewer 1 Report
Dear Authors,
I feel very happy that i had the opprtunity to peer-review the submitted manuscript entitled "Spinal cord injury treatment with mesenchymal stem cells – direct or indirect action?"
The manuscript comprises a very valuable review in the field of MSCs and spinal cord therapy. Below you will find my comments for the current manuscript.
1) I would expect a more sophisticated title for this manuscript.
2) In the introduction section, the authors need to add more details regarding the mechanism of spinal cord injury, which cells are affected, and what is the current golden standard therapeutic strategy.
3) The authors should change the term of Mesenchymal Stem Cells to Mesenchymal Stromal Cells to the whole manuscript. Based on the latest literature the Mesenchymal Stromal Cells have different characteristics from Mesenchymal Stem Cells, and the authors should define which cells are presenting and also the differences among the different populations.
4) The authors should revise the term of ISCT to International Society of Cell and Gene Therapy based on the latest literature (https://www.isctglobal.org/home).
5) The authors should focus in the sections 4. Paracrine effect of MSCs, 4.1. Secretome and 4.2. Extracellular vesicles (EVs) more details focused on their possible effect on spinal cord injury.
6) Also, in the same sections, the authors should discuss clinical trials performed in spinal cord injury. Also should include in each section tables showing the clinical trials.
The language quality of the current manuscript is fine. Only minor changes are required.
Author Response
Dear Reviewer,
Thank you for your insights and valuable comments. The manuscript has been proofread and the changes are visible using the “Track Changes” function.
At the same time, I am attaching my answers to your individual comments:
- I changed the title.
- In the introduction section, I expanded the information on a more detailed description of spinal cord injury (SCI) and listed the current methods of SCI treatment from the available literature.
- Thank you for the stimulating observation. I changed Mesenchymal stem cells to Mesenchyma stromal cells, as these terms are not interchangeable. However, while studying the literature and collecting information from it, I came across a similar problem, where most authors confuse these terms and it is not certain what specific type of cells they are talking about.
- I apologize for the mistake and corrected it to the correct name.
- + 6. I partially rewrote it. I preferred to write about clinical studies in the form of sentences rather than tables, because there are not so many of them, especially for SCI and secretome and EVs. And yes, thank you, that aspect was missing in this manuscript.
Thank you once again for the motivational words and comments,
Best regards,
Slovinská
Reviewer 2 Report
Review Report on "Spinal cord injury treatment with mesenchymal stem cells - direct or indirect action?" The title effectively introduces the topic of the article and raises the question of whether mesenchymal stem cell (MSC) therapy for spinal cord injury (SCI) involves a direct or indirect action. It is concise and informative.
Introduction
1. Expand on the cascade of pathophysiological events in the secondary phase of SCI, such as inflammation, excitotoxicity, and glial scar formation, to enhance the reader's understanding.
2. Specify the current limitations in existing treatment methods for SCI to highlight the need for more effective therapies.
Mesenchymal Stem Cells (MSCs):
1. Include additional references to support the statements about low immunogenicity and limited tumor development risks associated with MSCs.
2. Provide a comparative analysis of MSCs derived from various sources, such as bone marrow, adipose tissue, and umbilical cord, their regenerative and immuno-modulatory capabilities, highlighting their suitability for SCI treatment.
MSCs Therapy:
1. Discuss the challenges and potential risks associated with immunological reactions in allogeneic MSC therapy, such as graft-versus-host disease, to provide a more comprehensive analysis.
2. Include specific examples or studies demonstrating the differentiation potential of MSCs into neural cells or glial cells to strengthen the argument.
3. Provide more detailed information on the optimal doses, administration routes, and timing of MSC therapy based on existing studies to guide future research and clinical practice.
4. Include more information on the molecular mechanisms by which MSCs reduce pain and promote functional recovery, such as the modulation of inflammatory factors and the upregulation of neurotrophic factors.
MSCs with Biomaterials and Scaffold:
1. Provide more specific examples of biomaterials and scaffolds used in conjunction with MSCs, including their properties and their impact on MSC function and tissue regeneration.
2. Include references to studies that demonstrate the synergistic effects of MSCs and biomaterial scaffolds in promoting tissue repair and functional recovery in SCI models.
Paracrine Effect of MSCs:
1. Elaborate on the mechanisms underlying the poor engraftment of MSCs in the presence of chondroitin sulfated proteoglycans (CSPG) and its implications for MSC therapy.
2. Provide more information on the molecular mechanisms by which MSCs modulate the immune response, including the effects on cytokine profiles and macrophage polarization.
Secretome:
1. Discuss specific examples of bioactive molecules within the secretome and their effects on tissue repair, neuroprotection, angiogenesis, and immunomodulation.
2. Elaborate on the specific soluble factors or molecules within the secretome that contribute to immunosuppression, such as interleukins or immunomodulatory proteins.
Extracellular Vesicles (EVs):
1. Provide more specific details on the biogenesis, cargo content, and mechanisms of action of EVs to enhance the reader's understanding.
2. Include references to studies demonstrating the therapeutic effects of MSC-derived EVs in preclinical or clinical models of SCI and other neurological disorders.
Conclusion:
1. Strengthen the conclusion by emphasizing the potential impact of MSC-based therapies and the importance of ongoing research in addressing the current limitations and challenges.
2. Elaborate on the specific areas of research needed, such as standardization of MSC therapy protocols, identification of key biomolecules within the secretome, and development of targeted delivery methods for EVs.
3. Provide specific examples or potential future directions for the use of MSC-based therapies in diagnostics or therapeutics, beyond SCI, such as neurodegenerative diseases or tissue regeneration.
4. Emphasize the potential of MSC-based therapies and their products in transforming the field of SCI treatment and improving patient outcomes.
By addressing these points of improvement, the overall final conclusion of the review will be strengthened, providing a more comprehensive and scientific support.
Author Response
Dear Reviewer,
Thank you very much for the encouraging words and very valuable opinion.
The manuscript has been proofread and the changes are visible using the “Track Changes” function. At the same time, I am attaching my answers to your individual comments:
Introduction: I expanded the information.
Mesenchymal stem cells (MSCs): I included additional references and provided a comparative analysis according to your recommendation.
MSCs therapy: I add detailed facts about allogeneic MSCs, examples of MSCs differentiation potential into neural cells, and how MSCs are involved in pain reduction.
MSCs with biomaterials and scaffold: I provided more particular examples of biomaterials used in SCI experiments and therapy to promote tissue repair after SCI.
Paracrine effect of MSCs: Information about chondroitin sulfated proteoglycans and their inhibition effect on transplanted MSCs has been added.
Secretome: I have supplemented the information as necessary.
Extracellular vesicles: Basically, the information about EVs biogenesis in the article was intended only as an illustration, and that is why they were so supportive and illustrative for the reader, as it is a rather broad topic worthy of another new article. And yes, thank you, that aspect of clinical models of SCI and EVs was missing in this manuscript, so I added it according to your recommendation.
Conclusion: Individual comments were individually included in separate sections.
Thank you once again for your valuable comments, thanks to which this manuscript, I hope, could be useful for other scientists and their work.
Best regards,
Slovinska
Reviewer 3 Report
This review covers a fundamental topic in the investigation of mesenchymal stem cells (MSCs) related to the spinal cord injury. This review is well written and covers a large amount of papers in the field.
It also suggests some new frontiers in the investigation that might inspire future publications.
I so recommend this review for publication.
Kind regards,
The language is accurate and no major mistakes have been detected.
Best,
Author Response
Dear Reviewer,
Thank you very much for the encouraging words and very valuable opinion. I hope that the manuscript could be useful for other scientists and their work.
Best regards,
Slovinská
Round 2
Reviewer 1 Report
Dear authors,
You have performed a great job performing the revisions of the current manuscritp. I am very satisfied with the revised manuscript.
Good work!!
Reviewer 2 Report
The improvements are noticeable. I conclude for accept in the present form.
