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March 06, 2025, 03:11

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The authors should provide adequate legends for each figure. Some parts of the paper are just a listing of facts and are poorly organized or discussed. The table in the paper is well organized and suited. A table to compare the pros and cons of different kinds of stem cells for muscle atrophy therapy will be helpful.

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04382883

March 04, 2025, 16:00

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Stem Cell Therapy: A New Hope for Patients with Skeletal Muscle Atrophy? Skeletal muscle atrophy refers to the reduction or loss of muscle fibers due to nutritional deficiencies or diseases, leading to a decline in muscle mass. Current studies indicate that skeletal muscle atrophy is closely associated with an imbalance between protein synthesis and degradation, driven by multiple factors such as inflammation, oxidative stress, autophagy, and apoptosis [1-3]. Due to the complexity of its molecular mechanisms, effective therapeutic strategies are lacking, and traditional approaches like rehabilitation training and pharmacological interventions show limited efficacy. Therefore, exploring more effective treatments is imperative. Stem cell therapy, with its unique regenerative potential and immunomodulatory properties, offers a promising avenue for treating this condition. In the current issue of the World Journal of Stem Cells, Ying-Jie Wang and colleagues published a review titled "Stem Cell Therapy: A Promising Therapeutic Approach for Skeletal Muscle Atrophy." The article summarizes the molecular mechanisms of muscle atrophy and highlights the applications of mesenchymal stem cells (MSCs), induced pluripotent stem cells (iPSCs), and their derivatives (e.g., exosomes) in treating skeletal muscle atrophy. These stem cells exert therapeutic effects by modulating inflammation, promoting angiogenesis, suppressing oxidative stress, and facilitating muscle regeneration. The authors also address challenges in clinical translation, including immune rejection, tumorigenic risks, inefficient stem cell homing, and the absence of standardized protocols. Despite these hurdles, the review expresses optimism about the future of stem cell therapy, particularly emphasizing the superior potential of stem cell-derived acellular therapies (e.g., exosomes) over traditional cell transplantation. We maintain a cautiously optimistic view regarding the prospects of stem cell therapy for skeletal muscle atrophy. While stem cell-based approaches, especially MSC- and exosome-based strategies, demonstrate promising safety and efficacy [4, 5], several issues must be resolved. These include addressing heterogeneity in stem cell sources, ensuring long-term safety, and establishing standardized protocols for clinical translation. Although iPSCs circumvent ethical concerns, their differentiation and purification techniques require optimization, and potential genetic mutations remain a concern. Exosomes, as acellular therapeutics, may reduce immune reactions; however, challenges in large-scale production and quality control persist. Therapeutic Potential of Stem Cells Stem cell therapy exhibits multidimensional potential in treating muscle atrophy. First, its mechanisms are highly synergistic: MSCs and iPSCs improve the muscle microenvironment by regulating inflammatory cytokines (e.g., suppressing IL-6 and TNF-α), promoting angiogenesis, inhibiting oxidative stress, and enhancing autophagy. Exosomes further amplify therapeutic effects by delivering functional miRNAs (e.g., miR-132-3p/FoxO3 axis) to delay protein degradation and stimulate regeneration [4, 6]. Second, exosomes as acellular carriers broaden clinical applicability: MSC-derived exosomes (e.g., hUC-MSC-Exos, ADSC-Exos) avoid immune rejection and tumorigenic risks associated with live cell transplantation. Their high biocompatibility and cargo of bioactive molecules (e.g., circHIPK3, AMPK/ULK1 regulators) enable targeted intervention in diabetes- or neuropathy-related atrophy, positioning them as pivotal tools for clinical translation [6, 7]. Third, iPSCs hold exceptional promise for personalized medicine. Their ability to differentiate into myogenic progenitor cells (MPCs) or motor neurons facilitates the reconstruction of neuromuscular junctions, offering precise repair for genetic atrophy (e.g., facioscapulohumeral muscular dystrophy, FSHD). While autologous iPSCs mitigate immune rejection, clinical application demands improved differentiation efficiency and safety [8, 9]. Current Challenges and Solutions Clinical translation of stem cell therapy faces multiple challenges requiring innovative solutions. First, heterogeneity and standardization: MSC efficacy varies with donor age, tissue source (e.g., bone marrow, adipose, umbilical cord), and culture conditions [10]. Establishing unified quality control standards—via surface marker screening, secretome profiling, and single-cell sequencing—is critical to identify functional subpopulations and enable precision manufacturing [11]. Second, genetic instability and differentiation inefficiency hinder iPSC applications: reprogramming-induced mutations and inconsistent differentiation protocols (transgene-dependent or -independent) limit reliability [12]. Integrating non-integrative methods (e.g., mRNA reprogramming) and 3D organoid culture systems may optimize differentiation pathways [8]. Third, exosome scalability and targeting: natural exosomes suffer from low bioactive content and short half-lives. Engineering strategies (e.g., ligand modification or drug loading) can enhance tissue-specific delivery [13, 14], while microfluidic-nanocarrier systems may resolve production bottlenecks. Finally, accelerating clinical translation: preclinical studies predominantly rely on animal models; multicenter trials are needed to validate long-term safety (e.g., tumorigenicity, immune tolerance) [15, 16]. Combining stem cell therapy with anti-inflammatory agents (e.g., IL-1β inhibitors), rehabilitation, or gene editing (e.g., CRISPR-Cas9) may synergistically enhance efficacy [17, 18]. Future Directions Future research should prioritize interdisciplinary integration and precision strategies. First, mechanistic insights: single-cell and spatial transcriptomics can unravel dynamic interactions between stem cells and the muscle microenvironment (e.g., satellite cells, macrophages), identifying key regulatory nodes (e.g., Wnt/β-catenin, PI3K/Akt pathways) [3, 19]. Second, biomaterial innovations: smart hydrogels or electroconductive scaffolds combined with localized stem cell/exosome delivery systems could enhance homing efficiency and functional persistence [20, 21]. Third, personalized approaches: tailored therapies based on disease-specific etiologies (e.g., ALS, diabetic atrophy) and molecular subtypes (e.g., inflammatory signatures) are essential. For instance, AMPK-activated umbilical cord MSCs may rectify metabolic dysregulation in diabetic atrophy [22, 23]. Lastly, ethical and regulatory frameworks: international guidelines must standardize stem cell therapies and clarify regulatory classifications (e.g., exosomes as "drugs") to accelerate clinical translation. Stem cell therapy for skeletal muscle atrophy is transitioning from bench to bedside, yet critical hurdles—standardization, safety, and efficacy validation—remain. Integrating multidisciplinary technologies (e.g., synthetic biology, bioinformatics) and advancing translational research will bridge the gap between "laboratory breakthroughs" and "patient benefits." References: 1. Zhang, H., et al., Oxidative stress: Roles in skeletal muscle atrophy. Biochem Pharmacol, 2023. 214: p. 115664. 2. Ji, Y., et al., Inflammation: Roles in Skeletal Muscle Atrophy. Antioxidants (Basel), 2022. 11(9). 3. Liang, W., et al., Epigenetic control of skeletal muscle atrophy. Cell Mol Biol Lett, 2024. 29(1): p. 99. 4. Huang, Z., et al., Skeletal Muscle Atrophy Was Alleviated by Salidroside Through Suppressing Oxidative Stress and Inflammation During Denervation. Front Pharmacol, 2019. 10: p. 997. 5. Song, J., et al., Mesenchymal stromal cells ameliorate diabetes-induced muscle atrophy through exosomes by enhancing AMPK/ULK1-mediated autophagy. J Cachexia Sarcopenia Muscle, 2023. 14(2): p. 915-929. 6. Archacka, K., et al., Hypoxia preconditioned bone marrow-derived mesenchymal stromal/stem cells enhance myoblast fusion and skeletal muscle regeneration. Stem Cell Res Ther, 2021. 12(1): p. 448. 7. Leong, J., et al., Surface Tethering of Inflammation-Modulatory Nanostimulators to Stem Cells for Ischemic Muscle Repair. ACS Nano, 2020. 14(5): p. 5298-5313. 8. Kim, H., et al., Genomic Safe Harbor Expression of PAX7 for the Generation of Engraftable Myogenic Progenitors. Stem Cell Reports, 2021. 16(1): p. 10-19. 9. Azzag, K., et al., Transplantation of PSC-derived myogenic progenitors counteracts disease phenotypes in FSHD mice. NPJ Regen Med, 2022. 7(1): p. 43. 10. Li, J., et al., The heterogeneity of mesenchymal stem cells: an important issue to be addressed in cell therapy. Stem Cell Res Ther, 2023. 14(1): p. 381. 11. Oguma, Y., et al., Single-cell RNA sequencing reveals different signatures of mesenchymal stromal cell pluripotent-like and multipotent populations. iScience, 2022. 25(11): p. 105395. 12. Shamsian, A., et al., Cancer cells as a new source of induced pluripotent stem cells. Stem Cell Res Ther, 2022. 13(1): p. 459. 13. Rezaie, J., et al., Mesenchymal stem cells derived extracellular vesicles: A promising nanomedicine for drug delivery system. Biochem Pharmacol, 2022. 203: p. 115167. 14. Yang, Q., et al., Exosomes-loaded electroconductive nerve dressing for nerve regeneration and pain relief against diabetic peripheral nerve injury. Bioact Mater, 2023. 26: p. 194-215. 15. Drela, K., et al., Experimental Strategies of Mesenchymal Stem Cell Propagation: Adverse Events and Potential Risk of Functional Changes. Stem Cells Int, 2019. 2019: p. 7012692. 16. Deuse, T., et al., Hypoimmunogenic derivatives of induced pluripotent stem cells evade immune rejection in fully immunocompetent allogeneic recipients. Nat Biotechnol, 2019. 37(3): p. 252-258. 17. Iyer, S.R., et al., Exosomes Isolated From Platelet-Rich Plasma and Mesenchymal Stem Cells Promote Recovery of Function After Muscle Injury. Am J Sports Med, 2020. 48(9): p. 2277-2286. 18. Chang, M., et al., Duchenne muscular dystrophy: pathogenesis and promising therapies. J Neurol, 2023. 270(8): p. 3733-3749. 19. Sartori, R., V. Romanello, and M. Sandri, Mechanisms of muscle atrophy and hypertrophy: implications in health and disease. Nat Commun, 2021. 12(1): p. 330. 20. Luo, W., et al., Biomaterials-Based Technologies in Skeletal Muscle Tissue Engineering. Adv Healthc Mater, 2024. 13(18): p. e2304196. 21. Shan, Y., et al., Pharmacokinetic characteristics of mesenchymal stem cells in translational challenges. Signal Transduct Target Ther, 2024. 9(1): p. 242. 22. Shen, Y., et al., Diabetic Muscular Atrophy: Molecular Mechanisms and Promising Therapies. Front Endocrinol (Lausanne), 2022. 13: p. 917113. 23. Yeo, C.J.J., E.F. Tizzano, and B.T. Darras, Challenges and opportunities in spinal muscular atrophy therapeutics. Lancet Neurol, 2024. 23(2): p. 205-218.

First, thank you very much for your professional comments on the article published in World Journal of Stem Cells. Second, we read your comments with great interest. You are welcome to format your valuable comments into a Letter to the Editor and submit it online to World Journal of Stem Cells at https://www.f6publishing.com. There are no restrictions on the number of words, figures (color, B/W) or authors for a Letter to the Editor. In addition, the article processing charge will be exempted for this Letter to the Editor. As with all articles published by the Baishideng Publishing Group, the Letter to the Editor will be published online after completing peer review. The guidelines for a Letter to the Editor can be found at: https://www.wjgnet.com/bpg/GerInfo/219. Finally, we look forward to receiving your high-quality Letter to the Editor, which will promote academic communication and lead the development of this discipline.

08462443

February 24, 2025, 14:12

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Suggested Title:From Weakness to Wellness: The Role of Stem Cells in Muscle Atrophy Recovery A. Clarity and Conciseness • Some sections, particularly those on molecular mechanisms, are dense and could benefit from simplification or restructuring. B. Novelty and Critical Analysis • The review summarizes existing knowledge well but lacks critical analysis of conflicting findings. • Consider discussing limitations of existing studies, such as sample size issues in preclinical models, potential biases, and reproducibility concerns. • More emphasis could be placed on recent breakthroughs or innovative approaches in stem cell therapy, particularly in clinical trials. C. Clinical Relevance and Future Directions • The discussion of clinical applications is somewhat broad. It would be beneficial to include: o Specific ongoing clinical trials (if available). o A comparison of animal models vs. human studies to highlight translational challenges. • The challenges section should offer potential solutions or strategies to overcome issues like immune rejection, tumorigenicity, and ethical concerns. D. Specific Suggestions for Improvement • Introduction: Emphasize the gap in current treatments that stem cell therapy aims to address. • Current Treatment Strategies: Compare rehabilitation and pharmacological treatments with stem cell therapy in terms of: Efficacy, Limitations, Side effects. • Exosome Therapy: This part is well-detailed, but it could benefit from a discussion on manufacturing challenges and standardization issues for clinical application. • Conclusion: Strengthen the future perspectives by suggesting research directions or potential improvements in stem cell delivery methods.

First, thank you very much for your professional comments on the article published in World Journal of Stem Cells. Second, we read your comments with great interest. You are welcome to format your valuable comments into a Letter to the Editor and submit it online to World Journal of Stem Cells at https://www.f6publishing.com. There are no restrictions on the number of words, figures (color, B/W) or authors for a Letter to the Editor. In addition, the article processing charge will be exempted for this Letter to the Editor. As with all articles published by the Baishideng Publishing Group, the Letter to the Editor will be published online after completing peer review. The guidelines for a Letter to the Editor can be found at: https://www.wjgnet.com/bpg/GerInfo/219. Finally, we look forward to receiving your high-quality Letter to the Editor, which will promote academic communication and lead the development of this discipline.