Aging-related changes of miR-23b-3p expression in extracellular vesicles from mesenchymal stromal cells affect TGFBR3 signaling
Abstract Extracellular vesicles (EVs), which carry biological mediators such as microRNAs (miRNAs) and cytokines, play a crucial role in regulating recipient tissues and are considered a key mechanism of action in cell therapy. However, it has been found that cellular aging in donor cells significan...
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Nature Portfolio
2025-07-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-025-06982-y |
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| author | Maki Itokazu Toshiyuki Takehara Kensuke Toriumi Natsumi Iwawaki Tatsufumi Mori Yuta Ondoera Yuji Higashimoto Koji Goto Hidekazu Yamada Takeshi Teramura |
| author_facet | Maki Itokazu Toshiyuki Takehara Kensuke Toriumi Natsumi Iwawaki Tatsufumi Mori Yuta Ondoera Yuji Higashimoto Koji Goto Hidekazu Yamada Takeshi Teramura |
| author_sort | Maki Itokazu |
| collection | DOAJ |
| description | Abstract Extracellular vesicles (EVs), which carry biological mediators such as microRNAs (miRNAs) and cytokines, play a crucial role in regulating recipient tissues and are considered a key mechanism of action in cell therapy. However, it has been found that cellular aging in donor cells significantly affects the expression profiles of these mediators involved in intercellular communication. In this study, we identified miR-23b-3p as a regulator of stemness-associated genes through its targeting of TGFBR3, with its expression differing between mesenchymal stem cells (MSCs) from young and aged donors. In aged MSCs, hypermethylation of the human MIR23B promoter region led to its downregulation. Treatment with the demethylating agent valproic acid restored miR-23b-3p expression and facilitated its incorporation into EVs. Our findings indicate that aging in MSCs alters the miRNA composition of EVs, potentially disrupting intercellular communication and significantly impacting the therapeutic efficacy of cell transplantation. To address this issue, the induction of demethylation may represent a promising strategy to improve treatment outcomes of MSCs. |
| format | Article |
| id | doaj-art-c43da32ce35e4f25b90be2c3fb034b73 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-c43da32ce35e4f25b90be2c3fb034b732025-08-20T04:01:34ZengNature PortfolioScientific Reports2045-23222025-07-0115111210.1038/s41598-025-06982-yAging-related changes of miR-23b-3p expression in extracellular vesicles from mesenchymal stromal cells affect TGFBR3 signalingMaki Itokazu0Toshiyuki Takehara1Kensuke Toriumi2Natsumi Iwawaki3Tatsufumi Mori4Yuta Ondoera5Yuji Higashimoto6Koji Goto7Hidekazu Yamada8Takeshi Teramura9Department of Rehabilitation Medicine, Kindai University Faculty of MedicineDivision of Cell Biology for Regenerative Medicine, Institute of Advanced Clinical Medicine, Kindai University Faculty of MedicineDepartment of Orthopaedic Surgery, Kindai University Faculty of MedicineDivision of Cell Biology for Regenerative Medicine, Institute of Advanced Clinical Medicine, Kindai University Faculty of MedicineKindai University Life Science Research Institute, Kindai UniversityDivision of Cell Biology for Regenerative Medicine, Institute of Advanced Clinical Medicine, Kindai University Faculty of MedicineDepartment of Rehabilitation Medicine, Kindai University Faculty of MedicineDepartment of Orthopaedic Surgery, Kindai University Faculty of MedicineKindai Univeristy Anti-Aging CenterDivision of Cell Biology for Regenerative Medicine, Institute of Advanced Clinical Medicine, Kindai University Faculty of MedicineAbstract Extracellular vesicles (EVs), which carry biological mediators such as microRNAs (miRNAs) and cytokines, play a crucial role in regulating recipient tissues and are considered a key mechanism of action in cell therapy. However, it has been found that cellular aging in donor cells significantly affects the expression profiles of these mediators involved in intercellular communication. In this study, we identified miR-23b-3p as a regulator of stemness-associated genes through its targeting of TGFBR3, with its expression differing between mesenchymal stem cells (MSCs) from young and aged donors. In aged MSCs, hypermethylation of the human MIR23B promoter region led to its downregulation. Treatment with the demethylating agent valproic acid restored miR-23b-3p expression and facilitated its incorporation into EVs. Our findings indicate that aging in MSCs alters the miRNA composition of EVs, potentially disrupting intercellular communication and significantly impacting the therapeutic efficacy of cell transplantation. To address this issue, the induction of demethylation may represent a promising strategy to improve treatment outcomes of MSCs.https://doi.org/10.1038/s41598-025-06982-y |
| spellingShingle | Maki Itokazu Toshiyuki Takehara Kensuke Toriumi Natsumi Iwawaki Tatsufumi Mori Yuta Ondoera Yuji Higashimoto Koji Goto Hidekazu Yamada Takeshi Teramura Aging-related changes of miR-23b-3p expression in extracellular vesicles from mesenchymal stromal cells affect TGFBR3 signaling Scientific Reports |
| title | Aging-related changes of miR-23b-3p expression in extracellular vesicles from mesenchymal stromal cells affect TGFBR3 signaling |
| title_full | Aging-related changes of miR-23b-3p expression in extracellular vesicles from mesenchymal stromal cells affect TGFBR3 signaling |
| title_fullStr | Aging-related changes of miR-23b-3p expression in extracellular vesicles from mesenchymal stromal cells affect TGFBR3 signaling |
| title_full_unstemmed | Aging-related changes of miR-23b-3p expression in extracellular vesicles from mesenchymal stromal cells affect TGFBR3 signaling |
| title_short | Aging-related changes of miR-23b-3p expression in extracellular vesicles from mesenchymal stromal cells affect TGFBR3 signaling |
| title_sort | aging related changes of mir 23b 3p expression in extracellular vesicles from mesenchymal stromal cells affect tgfbr3 signaling |
| url | https://doi.org/10.1038/s41598-025-06982-y |
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