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| Content Provider | Springer Nature : BioMed Central |
|---|---|
| Author | Li, Yanju Liu, Yang Yang, Xu Yang, Bo Cheng, Jinyang Chen, Juan Yuan, Xiaoshuang Xu, Xiao Liu, Guangyang He, Zhixu Wang, Feiqing |
| Abstract | Background The therapeutic benefits of mesenchymal stromal cells (MSCs) are largely dependent on paracrine factors, but the supernatants of the different MSCs may have different effects on multiple myeloma (MM) cells. Therefore, this study compared supernatants of bone marrow-derived mesenchymal stromal cells (BM-MSCs) with umbilical cord wharton’s jelly’s mesenchymal stem cells (UC-WJ MSCs) in different states (non-senescent and replicative senescence) on the MM cells. Methods We extracted human BM-MSCs and UC-WJ MSCs in vitro and used H2O2 to induce replicative senescence. Concentrated supernatants from MSCs and senescent MSCs (SMSCs) were added to MM cells. Cell proliferation, the cell cycle, apoptosis, cell migration, tumor stemness factor expression, and cytokine expression levels were analyzed. Transcription regulation of signaling pathways was discussed. Results We successfully isolated and identified BM-MSCs, UC-WJ MSCs, and SMSCs. When concentrated supernatants from BM-MSCs, UC-WJ MSCs, senescent BM-MSCs (SBM-MSCs), senescent UCWJ MSCs (SUC-WJ MSCs) were used to treat MM cells, BMMSCs and SBM-MSCs supernatants promoted the proliferation of MM cells, with a more pronounced effect by SBM-MSCs. UC-WJ MSCs and SUC-WJ MSCs supernatants inhibited the viability and proliferation of MM cells. BM-MSCs and SBM-MSCs supernatants increased the proportion of MM cells in the S-phase, with the effect of SBM-MSCs being more evident. UC-WJ MSCs and SUC-WJ MSCs supernatants arrested MM cells in the G0/G1 phase. BM-MSCs and SBM-MSCs supernatants enhanced the migration and tumor stemness of MM cells, with SBMMSCs having a more dramatic effect. UC-WJ MSCs and SUC-WJ MSCs supernatants inhibited the migration and tumor stemness of MM cells, with UC-WJ MSCs having a more inhibitory effect. IL-6 and VEGFA expression correlated negatively with the survival of patients with MM according to online database analysis, in addition, we found that the expression of IL-6 and VEGFA was higher in MM patients through GEO database analysis. BM-MSCs and SBM-MSCs supernatants treatment increased the expression of IL-6 and VEGFA on MM cells, while UC-WJ MSCs and SUC-WJ MSCs supernatants inhibited their expression. Signal pathway validation showed that the biological function of MSCs in MM is closely related to the PI3K/AKT/NF-κB pathway. Conclusion The supernatants of BM-MSCs promote the proliferation of MM cells, On the contrary, the supernatants of UC-WJ MSCs inhibit MM cell proliferation. We observed that MSCs from different sources and different states have contrasting biological functions in MM cells. Furthermore, this research was provided to the optimal cancer gene therapy vector for MM was UC-WJ MSCs, even UC-WJ MSCs was in the state of senescence. |
| Related Links | https://stemcellres.biomedcentral.com/counter/pdf/10.1186/s13287-025-04222-8.pdf |
| Ending Page | 15 |
| Page Count | 15 |
| Starting Page | 1 |
| File Format | HTM / HTML |
| ISSN | 17576512 |
| DOI | 10.1186/s13287-025-04222-8 |
| Journal | Stem Cell Research & Therapy |
| Issue Number | 1 |
| Volume Number | 16 |
| Language | English |
| Publisher | BioMed Central |
| Publisher Date | 2025-02-25 |
| Access Restriction | Open |
| Subject Keyword | Stem Cells Cell Biology Regenerative Medicine Tissue Engineering Biomedical Engineering and Bioengineering Mesenchymal stem cells Senescence Multiple myeloma Biological functions PI3K/AKT/NF-κB Regenerative Medicine/Tissue Engineering |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Medicine Biochemistry, Genetics and Molecular Biology Molecular Medicine |
| Journal Impact Factor | 7.1/2023 |
| 5-Year Journal Impact Factor | 7.9/2023 |
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