Mesenchymal stem cells alleviate dexamethasone-induced muscle atrophy in mice and the involvement of ERK1/2 signalling pathway
Abstract Background High dosage of dexamethasone (Dex) is an effective treatment for multiple diseases; however, it is often associated with severe side effects including muscle atrophy, resulting in higher risk of falls and poorer life quality of patients. Cell therapy with mesenchymal stem cells (...
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| Format: | Article |
| Language: | English |
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BMC
2023-08-01
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| Series: | Stem Cell Research & Therapy |
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| Online Access: | https://doi.org/10.1186/s13287-023-03418-0 |
| _version_ | 1827635306457726976 |
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| author | Belle Yu-Hsuan Wang Allen Wei-Ting Hsiao Hoi Ting Shiu Nicodemus Wong Amanda Yu-Fan Wang Chien-Wei Lee Oscar Kuang-Sheng Lee Wayne Yuk-Wai Lee |
| author_facet | Belle Yu-Hsuan Wang Allen Wei-Ting Hsiao Hoi Ting Shiu Nicodemus Wong Amanda Yu-Fan Wang Chien-Wei Lee Oscar Kuang-Sheng Lee Wayne Yuk-Wai Lee |
| author_sort | Belle Yu-Hsuan Wang |
| collection | DOAJ |
| description | Abstract Background High dosage of dexamethasone (Dex) is an effective treatment for multiple diseases; however, it is often associated with severe side effects including muscle atrophy, resulting in higher risk of falls and poorer life quality of patients. Cell therapy with mesenchymal stem cells (MSCs) holds promise for regenerative medicine. In this study, we aimed to investigate the therapeutic efficacy of systemic administration of adipose-derived mesenchymal stem cells (ADSCs) in mitigating the loss of muscle mass and strength in mouse model of DEX-induced muscle atrophy. Methods 3-month-old female C57BL/6 mice were treated with Dex (20 mg/kg body weight, i.p.) for 10 days to induce muscle atrophy, then subjected to intravenous injection of a single dose of ADSCs ( $$1\times {10}^{6}$$ 1 × 10 6 cells/kg body weight) or vehicle control. The mice were killed 7 days after ADSCs treatment. Body compositions were measured by animal DXA, gastrocnemius muscle was isolated for ex vivo muscle functional test, histological assessment and Western blot, while tibialis anterior muscles were isolated for RNA-sequencing and qPCR. For in vitro study, C2C12 myoblast cells were cultured under myogenic differentiation medium for 5 days following 100 $$\mu$$ μ M Dex treatment with or without ADSC-conditioned medium for another 4 days. Samples were collected for qPCR analysis and Western blot analysis. Myotube morphology was measured by myosin heavy chain immunofluorescence staining. Results ADSC treatment significantly increased body lean mass (10–20%), muscle wet weight (15–30%) and cross-sectional area (CSA) (~ 33%) in DEX-induced muscle atrophy mice model and down-regulated muscle atrophy-associated genes expression (45–65%). Hindlimb grip strength (~ 37%) and forelimb ex vivo muscle contraction property were significantly improved (~ 57%) in the treatment group. Significant increase in type I fibres (~ 77%) was found after ADSC injection. RNA-sequencing results suggested that ERK1/2 signalling pathway might be playing important role underlying the beneficial effect of ADSC treatment, which was confirmed by ERK1/2 inhibitor both in vitro and in vivo. Conclusions ADSCs restore the pathogenesis of Dex-induced muscle atrophy with an increased number of type I fibres, stronger muscle strength, faster recovery rate and more anti-fatigue ability via ERK1/2 signalling pathway. The inhibition of muscle atrophy-associated genes by ADSCs offered this treatment as an intervention option for muscle-associated diseases. Taken together, our findings suggested that adipose-derived mesenchymal stem cell therapy could be a new treatment option for patient with Dex-induced muscle atrophy. |
| first_indexed | 2024-03-09T15:25:57Z |
| format | Article |
| id | doaj.art-0a2116ecbdfb4c19ba4b5b75edf479c0 |
| institution | Directory Open Access Journal |
| issn | 1757-6512 |
| language | English |
| last_indexed | 2024-03-09T15:25:57Z |
| publishDate | 2023-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Stem Cell Research & Therapy |
| spelling | doaj.art-0a2116ecbdfb4c19ba4b5b75edf479c02023-11-26T12:31:05ZengBMCStem Cell Research & Therapy1757-65122023-08-0114111310.1186/s13287-023-03418-0Mesenchymal stem cells alleviate dexamethasone-induced muscle atrophy in mice and the involvement of ERK1/2 signalling pathwayBelle Yu-Hsuan Wang0Allen Wei-Ting Hsiao1Hoi Ting Shiu2Nicodemus Wong3Amanda Yu-Fan Wang4Chien-Wei Lee5Oscar Kuang-Sheng Lee6Wayne Yuk-Wai Lee7Center for Neuromusculoskeletal Restorative Medicine, CUHK InnoHK CentresMusculoskeletal Research Laboratory, SH Ho Scoliosis Research Laboratory, Department of Orthopaedics and Traumatology, Faculty of Medicine, The Chinese University of Hong KongMusculoskeletal Research Laboratory, SH Ho Scoliosis Research Laboratory, Department of Orthopaedics and Traumatology, Faculty of Medicine, The Chinese University of Hong KongCenter for Neuromusculoskeletal Restorative Medicine, CUHK InnoHK CentresMusculoskeletal Research Laboratory, SH Ho Scoliosis Research Laboratory, Department of Orthopaedics and Traumatology, Faculty of Medicine, The Chinese University of Hong KongCenter for Translational Genomics and Regenerative Medicine Research, China Medical University Hospital, China Medical UniversityCenter for Translational Genomics and Regenerative Medicine Research, China Medical University Hospital, China Medical UniversityCenter for Neuromusculoskeletal Restorative Medicine, CUHK InnoHK CentresAbstract Background High dosage of dexamethasone (Dex) is an effective treatment for multiple diseases; however, it is often associated with severe side effects including muscle atrophy, resulting in higher risk of falls and poorer life quality of patients. Cell therapy with mesenchymal stem cells (MSCs) holds promise for regenerative medicine. In this study, we aimed to investigate the therapeutic efficacy of systemic administration of adipose-derived mesenchymal stem cells (ADSCs) in mitigating the loss of muscle mass and strength in mouse model of DEX-induced muscle atrophy. Methods 3-month-old female C57BL/6 mice were treated with Dex (20 mg/kg body weight, i.p.) for 10 days to induce muscle atrophy, then subjected to intravenous injection of a single dose of ADSCs ( $$1\times {10}^{6}$$ 1 × 10 6 cells/kg body weight) or vehicle control. The mice were killed 7 days after ADSCs treatment. Body compositions were measured by animal DXA, gastrocnemius muscle was isolated for ex vivo muscle functional test, histological assessment and Western blot, while tibialis anterior muscles were isolated for RNA-sequencing and qPCR. For in vitro study, C2C12 myoblast cells were cultured under myogenic differentiation medium for 5 days following 100 $$\mu$$ μ M Dex treatment with or without ADSC-conditioned medium for another 4 days. Samples were collected for qPCR analysis and Western blot analysis. Myotube morphology was measured by myosin heavy chain immunofluorescence staining. Results ADSC treatment significantly increased body lean mass (10–20%), muscle wet weight (15–30%) and cross-sectional area (CSA) (~ 33%) in DEX-induced muscle atrophy mice model and down-regulated muscle atrophy-associated genes expression (45–65%). Hindlimb grip strength (~ 37%) and forelimb ex vivo muscle contraction property were significantly improved (~ 57%) in the treatment group. Significant increase in type I fibres (~ 77%) was found after ADSC injection. RNA-sequencing results suggested that ERK1/2 signalling pathway might be playing important role underlying the beneficial effect of ADSC treatment, which was confirmed by ERK1/2 inhibitor both in vitro and in vivo. Conclusions ADSCs restore the pathogenesis of Dex-induced muscle atrophy with an increased number of type I fibres, stronger muscle strength, faster recovery rate and more anti-fatigue ability via ERK1/2 signalling pathway. The inhibition of muscle atrophy-associated genes by ADSCs offered this treatment as an intervention option for muscle-associated diseases. Taken together, our findings suggested that adipose-derived mesenchymal stem cell therapy could be a new treatment option for patient with Dex-induced muscle atrophy.https://doi.org/10.1186/s13287-023-03418-0Mesenchymal stem cellMuscle atrophyDexamethasoneCell therapy |
| spellingShingle | Belle Yu-Hsuan Wang Allen Wei-Ting Hsiao Hoi Ting Shiu Nicodemus Wong Amanda Yu-Fan Wang Chien-Wei Lee Oscar Kuang-Sheng Lee Wayne Yuk-Wai Lee Mesenchymal stem cells alleviate dexamethasone-induced muscle atrophy in mice and the involvement of ERK1/2 signalling pathway Stem Cell Research & Therapy Mesenchymal stem cell Muscle atrophy Dexamethasone Cell therapy |
| title | Mesenchymal stem cells alleviate dexamethasone-induced muscle atrophy in mice and the involvement of ERK1/2 signalling pathway |
| title_full | Mesenchymal stem cells alleviate dexamethasone-induced muscle atrophy in mice and the involvement of ERK1/2 signalling pathway |
| title_fullStr | Mesenchymal stem cells alleviate dexamethasone-induced muscle atrophy in mice and the involvement of ERK1/2 signalling pathway |
| title_full_unstemmed | Mesenchymal stem cells alleviate dexamethasone-induced muscle atrophy in mice and the involvement of ERK1/2 signalling pathway |
| title_short | Mesenchymal stem cells alleviate dexamethasone-induced muscle atrophy in mice and the involvement of ERK1/2 signalling pathway |
| title_sort | mesenchymal stem cells alleviate dexamethasone induced muscle atrophy in mice and the involvement of erk1 2 signalling pathway |
| topic | Mesenchymal stem cell Muscle atrophy Dexamethasone Cell therapy |
| url | https://doi.org/10.1186/s13287-023-03418-0 |
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