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在小鼠模型中通过细胞疗法促进和加速肌肉再生。

Promoting and accelerating muscle regeneration through cell therapy in a mouse model.

作者信息

Salman Marwa I, Khalil Eman G, Almzaien Aous K, Hadi Ali A, Ahmed Aysar A, Shaker Hiba K, Al-Shammari Ahmed M

机构信息

Biotechnology Department, College of Science, Baghdad University, Baghdad, Iraq.

Biomedical Engineering Department, Engineering College, Al-Nahrain University, Baghdad, Iraq.

出版信息

J Taibah Univ Med Sci. 2024 Sep 21;19(5):1011-1023. doi: 10.1016/j.jtumed.2024.09.004. eCollection 2024 Oct.

DOI:10.1016/j.jtumed.2024.09.004
PMID:39484055
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11526084/
Abstract

OBJECTIVES

Skeletal muscle injuries and disorders are universal clinical challenges with direct and indirect mechanisms and notable residual effects, such as prolonged, intense pain and physical disability. Stem cells, an innovative tool for cell therapy for musculoskeletal disorders, specifically promote skeletal muscle regeneration. This study was aimed at investigating the use of mesenchymal stem cells (MSCs) and their differentiated myocytes as a cell-based therapy to promote regeneration in damaged or diseased skeletal muscle.

METHODS

Bone marrow mesenchymal stem cells (BM-MSCs) were isolated from the bone marrow of adult mice and grown in tissue culture flasks. The BM-MSCs were positive for CD90 and CD105, and negative for CD45 and CD34. These cells were induced with specific differentiation medium to differentiate into a skeletal muscle cell lineage over 7 days. Skeletal muscle differentiation was characterized according to morphology through hematoxylin and eosin staining, and scanning electron microscopy. Immunostaining for Myf-6, myosin heavy chain (MHC), and desmin-specific factors for skeletal muscle development-was performed to confirm skeletal muscle differentiation. An study in a muscle injury model was used to evaluate cell therapy based on naïve stem cells and differentiated myocytes.

RESULTS

Cultured mouse BM-MSCS were positive for CD90 and CD105, and negative for CD45 and CD34. These cells developed into skeletal muscle with strong skeletal muscle differentiation potential, as confirmed by immunohistochemistry for the markers Myf6, MHC, and desmin. The differentiated myocytes showed better repair enhancement than undifferentiated stem cells after transplantations into a mouse model of skeletal muscle atrophy.

CONCLUSIONS

Myocytes derived from BM-MSCs may be incorporated into muscular atrophy treatment as a biological strategy for managing skeletal muscle diseases and injuries, thus advancing cell-based clinical treatments.

摘要

目的

骨骼肌损伤和疾病是普遍存在的临床挑战,具有直接和间接机制以及显著的残留影响,如长期剧烈疼痛和身体残疾。干细胞作为治疗肌肉骨骼疾病的一种创新细胞疗法工具,特别能促进骨骼肌再生。本研究旨在探讨间充质干细胞(MSCs)及其分化的肌细胞作为一种基于细胞的疗法,以促进受损或患病骨骼肌的再生。

方法

从成年小鼠骨髓中分离出骨髓间充质干细胞(BM-MSCs),并在组织培养瓶中培养。BM-MSCs对CD90和CD105呈阳性,对CD45和CD34呈阴性。这些细胞用特定的分化培养基诱导,在7天内分化为骨骼肌细胞谱系。通过苏木精和伊红染色以及扫描电子显微镜,根据形态学对骨骼肌分化进行表征。对Myf-6、肌球蛋白重链(MHC)和结蛋白(骨骼肌发育的特异性因子)进行免疫染色,以确认骨骼肌分化。在肌肉损伤模型中进行研究,以评估基于未分化干细胞和分化肌细胞的细胞疗法。

结果

培养的小鼠BM-MSCS对CD90和CD105呈阳性,对CD45和CD34呈阴性。通过对Myf6、MHC和结蛋白标志物的免疫组织化学证实,这些细胞发展为具有强大骨骼肌分化潜力的骨骼肌。将分化的肌细胞移植到骨骼肌萎缩小鼠模型中后,其显示出比未分化干细胞更好的修复增强效果。

结论

源自BM-MSCs的肌细胞可作为治疗骨骼肌疾病和损伤的生物学策略纳入肌肉萎缩治疗,从而推进基于细胞的临床治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67da/11526084/13450c4f1e56/gr8.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67da/11526084/d1082f9e1c9b/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67da/11526084/29fb49f76af4/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67da/11526084/e3ab1889276d/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67da/11526084/13450c4f1e56/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67da/11526084/18c68a79db90/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67da/11526084/4b08fd9080b9/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67da/11526084/da76e943d98a/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67da/11526084/8f64f5715b40/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67da/11526084/d1082f9e1c9b/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67da/11526084/29fb49f76af4/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67da/11526084/e3ab1889276d/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67da/11526084/13450c4f1e56/gr8.jpg

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