Uncovering impaired mitochondrial and lysosomal function in adipose-derived stem cells from obese individuals with altered biological activity
Abstract Background Adipose-derived stem cells (ADSCs) have been extensively used in preclinical and clinical trials for treating various diseases. However, the differences between ADSCs from lean individuals (L-ADSCs) and those from obese individuals (O-ADSCs) have not been thoroughly investigated,...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2024-01-01
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| Series: | Stem Cell Research & Therapy |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13287-023-03625-9 |
| _version_ | 1797355944463564800 |
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| author | Bo Wang Ge Zhang Yuwen Hu Ali Mohsin Zhimin Chen Weijie Hao Zhanxia Li Wei-Qiang Gao Meijin Guo Huiming Xu |
| author_facet | Bo Wang Ge Zhang Yuwen Hu Ali Mohsin Zhimin Chen Weijie Hao Zhanxia Li Wei-Qiang Gao Meijin Guo Huiming Xu |
| author_sort | Bo Wang |
| collection | DOAJ |
| description | Abstract Background Adipose-derived stem cells (ADSCs) have been extensively used in preclinical and clinical trials for treating various diseases. However, the differences between ADSCs from lean individuals (L-ADSCs) and those from obese individuals (O-ADSCs) have not been thoroughly investigated, particularly regarding their mitochondrial and lysosomal functions. Therefore, this study aims to evaluate the differences between L-ADSCs and O-ADSCs in terms of cell biological activity, mitochondria, and lysosomes. Methods We first isolated and cultured L-ADSCs and O-ADSCs. We then compared the differences between the two groups in terms of biological activity, including cell proliferation, differentiation potential, and their effect on the polarization of macrophages. Additionally, we observed the mitochondrial and lysosomal morphology of ADSCs using an electronic microscope, MitoTracker Red, and lysotracker Red dyes. We assessed mitochondrial function by examining mitochondrial membrane potential and membrane fluidity, antioxidative ability, and cell energy metabolism. Lysosomal function was evaluated by measuring autophagy and phagocytosis. Finally, we performed transcriptome analysis of the ADSCs using RNA sequencing. Results The biological activities of O-ADSCs were decreased, including cell immunophenotypic profiles, cell proliferation, and differentiation potential. Furthermore, compared to L-ADSCs, O-ADSCs promoted M1-type macrophage polarization and inhibited M2-type macrophage polarization. Additionally, the mitochondrial morphology of O-ADSCs was altered, with the size of the cells becoming smaller and mitochondrial fragments increasing. O-ADSCs also exhibited decreased mitochondrial membrane potential and membrane fluidity, antioxidative ability, and energy metabolism. With respect to lysosomes, O-ADSCs contained ungraded materials in their lysosomes, enhanced lysosomal permeability, and reduced autophagy and phagocytosis ability. RNA sequence analysis indicated that the signalling pathways related to cell senescence, cancer, and inflammation were upregulated, whereas the signalling pathways associated with stemness, cell differentiation, metabolism, and response to stress and stimuli were downregulated. Conclusions This study indicates that ADSCs from individuals (BMI > 30 kg/m2) exhibit impaired mitochondrial and lysosomal function with decreased biological activity. |
| first_indexed | 2024-03-08T14:19:29Z |
| format | Article |
| id | doaj.art-b8ed664eb15342dcaaf5becf44583ccb |
| institution | Directory Open Access Journal |
| issn | 1757-6512 |
| language | English |
| last_indexed | 2024-03-08T14:19:29Z |
| publishDate | 2024-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Stem Cell Research & Therapy |
| spelling | doaj.art-b8ed664eb15342dcaaf5becf44583ccb2024-01-14T12:13:45ZengBMCStem Cell Research & Therapy1757-65122024-01-0115111710.1186/s13287-023-03625-9Uncovering impaired mitochondrial and lysosomal function in adipose-derived stem cells from obese individuals with altered biological activityBo Wang0Ge Zhang1Yuwen Hu2Ali Mohsin3Zhimin Chen4Weijie Hao5Zhanxia Li6Wei-Qiang Gao7Meijin Guo8Huiming Xu9State Key Laboratory of Bioreactor Engineering, East China University of Science and TechnologyState Key Laboratory of Bioreactor Engineering, East China University of Science and TechnologyState Key Laboratory of Bioreactor Engineering, East China University of Science and TechnologyState Key Laboratory of Bioreactor Engineering, East China University of Science and TechnologyState Key Laboratory of Oncogenes and Related Genes, and Renji-MedX Clinical Stem Cell Research Center RenJi Hospital, Shanghai Jiao Tong University School of MedicineState Key Laboratory of Oncogenes and Related Genes, and Renji-MedX Clinical Stem Cell Research Center RenJi Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Respiratory Medicine, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of MedicineState Key Laboratory of Oncogenes and Related Genes, and Renji-MedX Clinical Stem Cell Research Center RenJi Hospital, Shanghai Jiao Tong University School of MedicineState Key Laboratory of Bioreactor Engineering, East China University of Science and TechnologyState Key Laboratory of Oncogenes and Related Genes, and Renji-MedX Clinical Stem Cell Research Center RenJi Hospital, Shanghai Jiao Tong University School of MedicineAbstract Background Adipose-derived stem cells (ADSCs) have been extensively used in preclinical and clinical trials for treating various diseases. However, the differences between ADSCs from lean individuals (L-ADSCs) and those from obese individuals (O-ADSCs) have not been thoroughly investigated, particularly regarding their mitochondrial and lysosomal functions. Therefore, this study aims to evaluate the differences between L-ADSCs and O-ADSCs in terms of cell biological activity, mitochondria, and lysosomes. Methods We first isolated and cultured L-ADSCs and O-ADSCs. We then compared the differences between the two groups in terms of biological activity, including cell proliferation, differentiation potential, and their effect on the polarization of macrophages. Additionally, we observed the mitochondrial and lysosomal morphology of ADSCs using an electronic microscope, MitoTracker Red, and lysotracker Red dyes. We assessed mitochondrial function by examining mitochondrial membrane potential and membrane fluidity, antioxidative ability, and cell energy metabolism. Lysosomal function was evaluated by measuring autophagy and phagocytosis. Finally, we performed transcriptome analysis of the ADSCs using RNA sequencing. Results The biological activities of O-ADSCs were decreased, including cell immunophenotypic profiles, cell proliferation, and differentiation potential. Furthermore, compared to L-ADSCs, O-ADSCs promoted M1-type macrophage polarization and inhibited M2-type macrophage polarization. Additionally, the mitochondrial morphology of O-ADSCs was altered, with the size of the cells becoming smaller and mitochondrial fragments increasing. O-ADSCs also exhibited decreased mitochondrial membrane potential and membrane fluidity, antioxidative ability, and energy metabolism. With respect to lysosomes, O-ADSCs contained ungraded materials in their lysosomes, enhanced lysosomal permeability, and reduced autophagy and phagocytosis ability. RNA sequence analysis indicated that the signalling pathways related to cell senescence, cancer, and inflammation were upregulated, whereas the signalling pathways associated with stemness, cell differentiation, metabolism, and response to stress and stimuli were downregulated. Conclusions This study indicates that ADSCs from individuals (BMI > 30 kg/m2) exhibit impaired mitochondrial and lysosomal function with decreased biological activity.https://doi.org/10.1186/s13287-023-03625-9Adipose-derived stem cellsObesityMitochondrial dysfunctionLysosomal dysfunction |
| spellingShingle | Bo Wang Ge Zhang Yuwen Hu Ali Mohsin Zhimin Chen Weijie Hao Zhanxia Li Wei-Qiang Gao Meijin Guo Huiming Xu Uncovering impaired mitochondrial and lysosomal function in adipose-derived stem cells from obese individuals with altered biological activity Stem Cell Research & Therapy Adipose-derived stem cells Obesity Mitochondrial dysfunction Lysosomal dysfunction |
| title | Uncovering impaired mitochondrial and lysosomal function in adipose-derived stem cells from obese individuals with altered biological activity |
| title_full | Uncovering impaired mitochondrial and lysosomal function in adipose-derived stem cells from obese individuals with altered biological activity |
| title_fullStr | Uncovering impaired mitochondrial and lysosomal function in adipose-derived stem cells from obese individuals with altered biological activity |
| title_full_unstemmed | Uncovering impaired mitochondrial and lysosomal function in adipose-derived stem cells from obese individuals with altered biological activity |
| title_short | Uncovering impaired mitochondrial and lysosomal function in adipose-derived stem cells from obese individuals with altered biological activity |
| title_sort | uncovering impaired mitochondrial and lysosomal function in adipose derived stem cells from obese individuals with altered biological activity |
| topic | Adipose-derived stem cells Obesity Mitochondrial dysfunction Lysosomal dysfunction |
| url | https://doi.org/10.1186/s13287-023-03625-9 |
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