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人骨髓间充质干细胞来源的骨骼肌细胞球体用于治疗地塞米松诱导的肌肉减少症。

Human Mesenchymal Stem Cell-Derived Skeletal Muscle Cell Spheroids for Treating Dexamethasone-Induced Sarcopenia.

作者信息

Yum Yoonji, Yoon Juhee, Nam Yu Hwa, Kang Duk-Hee, Jung Sung-Chul, Park Saeyoung

机构信息

Department of Biochemistry, College of Medicine, Ewha Womans University, 25 Magokdong-ro-2-gil, Gangseo-gu, Seoul, Republic of Korea.

Division of Nephrology, College of Medicine, Ewha Womans University, 25 Magokdong-ro-2-gil, Gangseo-gu, Seoul, 07804, Republic of Korea.

出版信息

Tissue Eng Regen Med. 2025 Sep 3. doi: 10.1007/s13770-025-00753-6.

Abstract

BACKGROUND

Sarcopenia, a musculoskeletal disease associated with aging or certain factors, is characterized by a reduction in muscle mass, strength, and performance. Dexamethasone (DEX)-induced muscular atrophy in animals, which shows a significant decrease in muscle mass, strength, and function, serves as a model for sarcopenia. Mesenchymal stem cell-based therapies, particularly those using 3D cultured spheroids, have emerged as a prominent area in muscle regeneration. Previous research has demonstrated that tonsil-derived mesenchymal stem cells (TMSCs) can differentiate into skeletal muscle cells (SKMCs) that exhibit attributes of skeletal muscles.

METHODS

Spheroids formed from TMSC-derived skeletal muscle cells (TMSC-SKMC-spheroids) were produced using microwells and subsequently transplanted into a sarcopenia model. This model utilized a dexamethasone (DEX)-induced muscular atrophy rat to mimic sarcopenia. The effectiveness of TMSC-SKMC-spheroid transplantation was assessed through grip strength tests, running fatigue tests, measurements of gastrocnemius muscle thickness and weight, and histopathological evaluations.

RESULTS

Post-transplantation, the rat models exhibited improvement in hind limb motor functions and gastrocnemius muscle regeneration. Additionally, the neuromuscular junctions in the gastrocnemius muscle of the transplantation group were restored.

CONCLUSION

These findings demonstrate the therapeutic potential of TMSC-SKMC-spheroids in the DEX-induced atrophy rat model and suggest their promise as a valuable therapeutic resource for sarcopenia caused by various factors.

摘要

背景

肌肉减少症是一种与衰老或某些因素相关的肌肉骨骼疾病,其特征是肌肉质量、力量和功能下降。地塞米松(DEX)诱导的动物肌肉萎缩表现为肌肉质量、力量和功能显著下降,可作为肌肉减少症的模型。基于间充质干细胞的疗法,特别是使用三维培养球体的疗法,已成为肌肉再生领域的一个突出研究方向。先前的研究表明,扁桃体来源的间充质干细胞(TMSCs)可以分化为具有骨骼肌特性的骨骼肌细胞(SKMCs)。

方法

使用微孔培养法制备由TMSC衍生的骨骼肌细胞形成的球体(TMSC-SKMC球体),随后将其移植到肌肉减少症模型中。该模型利用地塞米松(DEX)诱导的肌肉萎缩大鼠来模拟肌肉减少症。通过握力测试、跑步疲劳测试、腓肠肌厚度和重量测量以及组织病理学评估来评估TMSC-SKMC球体移植的有效性。

结果

移植后,大鼠模型的后肢运动功能和腓肠肌再生得到改善。此外,移植组腓肠肌中的神经肌肉接头也得以恢复。

结论

这些发现证明了TMSC-SKMC球体在DEX诱导的萎缩大鼠模型中的治疗潜力,并表明它们有望成为治疗各种因素引起的肌肉减少症的宝贵治疗资源。

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