PFKFB3-mediated glycometabolism reprogramming modulates endothelial differentiation and angiogenic capacity of placenta-derived mesenchymal stem cells
Abstract Background Mesenchymal stem cells (MSCs) have a great potential ability for endothelial differentiation, contributing to an effective means of therapeutic angiogenesis. Placenta-derived mesenchymal stem cells (PMSCs) have gradually attracted attention, while the endothelial differentiation...
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| Format: | Article |
| Language: | English |
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BMC
2022-08-01
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| Series: | Stem Cell Research & Therapy |
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| Online Access: | https://doi.org/10.1186/s13287-022-03089-3 |
| _version_ | 1817968046301511680 |
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| author | Yang Zhang Yanqi Zhong Weifang Liu Fanghui Zheng Yin Zhao Li Zou Xiaoxia Liu |
| author_facet | Yang Zhang Yanqi Zhong Weifang Liu Fanghui Zheng Yin Zhao Li Zou Xiaoxia Liu |
| author_sort | Yang Zhang |
| collection | DOAJ |
| description | Abstract Background Mesenchymal stem cells (MSCs) have a great potential ability for endothelial differentiation, contributing to an effective means of therapeutic angiogenesis. Placenta-derived mesenchymal stem cells (PMSCs) have gradually attracted attention, while the endothelial differentiation has not been fully evaluated in PMSCs. Metabolism homeostasis plays an important role in stem cell differentiation, but less is known about the glycometabolic reprogramming during the PMSCs endothelial differentiation. Hence, it is critical to investigate the potential role of glycometabolism reprogramming in mediating PMSCs endothelial differentiation. Methods Dil-Ac-LDL uptake assay, flow cytometry, and immunofluorescence were all to verify the endothelial differentiation in PMSCs. Seahorse XF Extracellular Flux Analyzers, Mito-tracker red staining, Mitochondrial membrane potential (MMP), lactate secretion assay, and transcriptome approach were to assess the variation of mitochondrial respiration and glycolysis during the PMSCs endothelial differentiation. Glycolysis enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) was considered a potential modulator for endothelial differentiation in PMSCs by small interfering RNA. Furthermore, transwell, in vitro Matrigel tube formation, and in vivo Matrigel plug assays were performed to evaluate the effect of PFKFB3-induced glycolysis on angiogenic capacities in this process. Results PMSCs possessed the superior potential of endothelial differentiation, in which the glycometabolic preference for glycolysis was confirmed. Moreover, PFKFB3-induced glycometabolism reprogramming could modulate the endothelial differentiation and angiogenic abilities of PMSCs. Conclusions Our results revealed that PFKFB3-mediated glycolysis is important for endothelial differentiation and angiogenesis in PMSCs. Our understanding of cellular glycometabolism and its regulatory effects on endothelial differentiation may propose and improve PMSCs as a putative strategy for clinical therapeutic angiogenesis. |
| first_indexed | 2024-04-13T20:03:53Z |
| format | Article |
| id | doaj.art-456f50b493964db5be081baa24eefbc5 |
| institution | Directory Open Access Journal |
| issn | 1757-6512 |
| language | English |
| last_indexed | 2024-04-13T20:03:53Z |
| publishDate | 2022-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Stem Cell Research & Therapy |
| spelling | doaj.art-456f50b493964db5be081baa24eefbc52022-12-22T02:32:06ZengBMCStem Cell Research & Therapy1757-65122022-08-0113112010.1186/s13287-022-03089-3PFKFB3-mediated glycometabolism reprogramming modulates endothelial differentiation and angiogenic capacity of placenta-derived mesenchymal stem cellsYang Zhang0Yanqi Zhong1Weifang Liu2Fanghui Zheng3Yin Zhao4Li Zou5Xiaoxia Liu6Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyAbstract Background Mesenchymal stem cells (MSCs) have a great potential ability for endothelial differentiation, contributing to an effective means of therapeutic angiogenesis. Placenta-derived mesenchymal stem cells (PMSCs) have gradually attracted attention, while the endothelial differentiation has not been fully evaluated in PMSCs. Metabolism homeostasis plays an important role in stem cell differentiation, but less is known about the glycometabolic reprogramming during the PMSCs endothelial differentiation. Hence, it is critical to investigate the potential role of glycometabolism reprogramming in mediating PMSCs endothelial differentiation. Methods Dil-Ac-LDL uptake assay, flow cytometry, and immunofluorescence were all to verify the endothelial differentiation in PMSCs. Seahorse XF Extracellular Flux Analyzers, Mito-tracker red staining, Mitochondrial membrane potential (MMP), lactate secretion assay, and transcriptome approach were to assess the variation of mitochondrial respiration and glycolysis during the PMSCs endothelial differentiation. Glycolysis enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) was considered a potential modulator for endothelial differentiation in PMSCs by small interfering RNA. Furthermore, transwell, in vitro Matrigel tube formation, and in vivo Matrigel plug assays were performed to evaluate the effect of PFKFB3-induced glycolysis on angiogenic capacities in this process. Results PMSCs possessed the superior potential of endothelial differentiation, in which the glycometabolic preference for glycolysis was confirmed. Moreover, PFKFB3-induced glycometabolism reprogramming could modulate the endothelial differentiation and angiogenic abilities of PMSCs. Conclusions Our results revealed that PFKFB3-mediated glycolysis is important for endothelial differentiation and angiogenesis in PMSCs. Our understanding of cellular glycometabolism and its regulatory effects on endothelial differentiation may propose and improve PMSCs as a putative strategy for clinical therapeutic angiogenesis.https://doi.org/10.1186/s13287-022-03089-3Mesenchymal stem cellsPlacentaEndothelial differentiationGlycometabolism reprogrammingGlycolysisPFKFB3 |
| spellingShingle | Yang Zhang Yanqi Zhong Weifang Liu Fanghui Zheng Yin Zhao Li Zou Xiaoxia Liu PFKFB3-mediated glycometabolism reprogramming modulates endothelial differentiation and angiogenic capacity of placenta-derived mesenchymal stem cells Stem Cell Research & Therapy Mesenchymal stem cells Placenta Endothelial differentiation Glycometabolism reprogramming Glycolysis PFKFB3 |
| title | PFKFB3-mediated glycometabolism reprogramming modulates endothelial differentiation and angiogenic capacity of placenta-derived mesenchymal stem cells |
| title_full | PFKFB3-mediated glycometabolism reprogramming modulates endothelial differentiation and angiogenic capacity of placenta-derived mesenchymal stem cells |
| title_fullStr | PFKFB3-mediated glycometabolism reprogramming modulates endothelial differentiation and angiogenic capacity of placenta-derived mesenchymal stem cells |
| title_full_unstemmed | PFKFB3-mediated glycometabolism reprogramming modulates endothelial differentiation and angiogenic capacity of placenta-derived mesenchymal stem cells |
| title_short | PFKFB3-mediated glycometabolism reprogramming modulates endothelial differentiation and angiogenic capacity of placenta-derived mesenchymal stem cells |
| title_sort | pfkfb3 mediated glycometabolism reprogramming modulates endothelial differentiation and angiogenic capacity of placenta derived mesenchymal stem cells |
| topic | Mesenchymal stem cells Placenta Endothelial differentiation Glycometabolism reprogramming Glycolysis PFKFB3 |
| url | https://doi.org/10.1186/s13287-022-03089-3 |
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