Thanh bên bài viết
Số lượt xem chi tiết bài báo: 22
Effects of TGF-β and dim on the secretion of growth factors into the culture medium by umbilical cord - derived mesenchymal stem cells
Nội dung chính của bài viết
Tóm tắt
Purpose: Mesenchymal stem cells (MSCs) and their secretome have been demonstrated to play an important role in regenerative medicine. In particular, the secretome, which consists of soluble factors and extracellular vesicles, including microvesicles and exosomes, is emerging as a promising cell-free alternative to MSCs because it is considered safer than cells while retaining comparable efficacy. However, the composition of this secretome is highly sensitive and influenced by multiple factors, including the type and source of the secreting cells, their physiological state, and the stimulating factors during cell culture. This study evaluates the expression of several growth factors secreted into the conditioned medium by umbilical cord-derived MSCs (UCMSCs) under stimulation with TGF-β and 3,3′-diindolylmethane (DIM).
Subjects and methods: UCMSCs were cultured at passage 5 (P5) and primed with TGF-β, DIM, and a combination of TGF-β and DIM. Conditioned media were collected and analyzed for the levels of key growth factors, including fibroblast growth factor-2 (FGF-2), hepatocyte growth factor (HGF), platelet-derived growth factor-BB (PDGF-BB), and vascular endothelial growth factor-A (VEGF-A), using Luminex assays.
Results: Results showed that FGF-2 and HGF expression remained consistent across all groups, with no significant differences, except that the HGF level in the TGF-β and DIM-primed group is greater than that in the from TGF-β-primed group. In contrast, TGF-β significantly increased the secretion of PDGF-BB and VEGF-A by USMCS compared with the control group (p < 0.05), highlighting its strong modulatory effect. DIM did not significantly alter growth factor levels. Additionally, the combination of TGF-β and DIM did not produce synergistic effects and even attenuated PDGF-BB secretion compared with TGF-β.
Conclusion: These findings demonstrate that TGF-β is a potent regulator of UCMSC secretome, enhancing the release of growth factors associated with tissue regeneration and angiogenesis, whereas DIM alone exerts minimal influence. Additionally, the absence of synergistic effects between TGF-β and DIM suggests a complex interplay between cellular signaling pathways. This study underscores the potential of TGF-β preconditioning as a strategy to optimize UCMSC secretome for regenerative medicine applications.
Chi tiết bài viết
Từ khóa
Umbilical cord-derived mesenchymal stem cells (UCMSCs), secretome, conditioned medium, stimulation, TGF-β, 3,3′-diindolylmethane (DIM), growth factors
Tài liệu tham khảo
2. Trigo, C.M., et al., Mesenchymal stem cell secretome for regenerative medicine: Where do we stand? Journal of Advanced Research, 2025. 70: p. 103-124.
3. Vu, D.M., et al., Effects of Extracellular Vesicles Secreted by TGFβ-Stimulated Umbilical Cord Mesenchymal Stem Cells on Skin Fibroblasts by Promoting Fibroblast Migration and ECM Protein Production. Biomedicines, 2022. 10(8).
4. Partan, R.U., et al., Umbilical Cord Mesenchymal Stem Cell Secretome Improves Clinical Outcomes and Changes Biomarkers in Knee Osteoarthritis. Journal of Clinical Medicine, 2023. 12(22): p. 7138.
5. Li, X., et al., Umbilical cord-derived mesenchymal stem cell secretome promotes skin regeneration and rejuvenation: From mechanism to therapeutics. Cell Prolif, 2024. 57(4): p. e13586.
6. Harrell, C.R., et al., Molecular Mechanisms Responsible for Therapeutic Potential of Mesenchymal Stem Cell-Derived Secretome. Cells, 2019. 8(5): p. 467.
7. Kavaldzhieva, K., et al., Mesenchymal Stem Cell Secretome: Potential Applications in Human Infertility Caused by Hormonal Imbalance, External Damage, or Immune Factors. Biomedicines, 2025. 13(3): p. 586.
8. Widaja, E., Pawitan, J. A., & Ramli, Y., Therapeutic potential of hUC-MSC secretome preconditioned with IFN-γ and/or TNF-α: An in vitro study on Alzheimer’s neuronal cell models. Narra J, 2025. 5(2): p. e288.
9. Bari, E., et al., Mesenchymal stem/stromal cell secretome for lung regeneration: The long way through “pharmaceuticalization” for the best formulation. Journal of Controlled Release, 2019. 309: p. 11-24.
10. Monsel, A., et al., Mesenchymal stem cell derived secretome and extracellular vesicles for acute lung injury and other inflammatory lung diseases. Expert Opin Biol Ther, 2016. 16(7): p. 859-71.
11. Arfianti, A., et al., Hipoxia modulates the secretion of growth factors of human umbilical cord-derived mesenchymal stem cells. Biomedicine (Taipei), 2023. 13(3): p. 49-56.
12. Miceli, V., et al., Different priming strategies improve distinct therapeutic capabilities of mesenchymal stromal/stem cells: Potential implications for their clinical use. World J Stem Cells, 2023. 15(5): p. 400-420.
13. Sun, J., et al., Transforming growth factor-β1 stimulates mesenchymal stem cell proliferation by altering cell cycle through FAK-Akt-mTOR pathway. Connect Tissue Res, 2019. 60(4): p. 406-417.
14. Shi, H., et al., 3,3'-Diindolylmethane stimulates exosomal Wnt11 autocrine signaling in human umbilical cord mesenchymal stem cells to enhance wound healing. Theranostics, 2017. 7(6): p. 1674-1688.
15. Le, H.M., et al., Differential development of umbilical cord-derived mesenchymal stem cells during long-term maintenance in fetal bovine serum-supplemented medium and xeno- and serum-free culture medium. Cellular Reprogramming, 2021. 23(6): p. 359-369.
16. Eiselleova, L., et al., A complex role for FGF-2 in self-renewal, survival, and adhesion of human embryonic stem cells. Stem Cells, 2009. 27(8): p. 1847-57.
17. Matsumoto, K. and T. Nakamura, HGF in regenerative medicine: Roles in regeneration system and potential therapeutic application. 2001. 15: p. 95-104.
18. Wang, Z., et al., Antifibrotic Effects of Hepatocyte Growth Factor on Endothelial-to-Mesenchymal Transition via Transforming Growth Factor-Beta1 (TGF-β1)/Smad and Akt/mTOR/P70S6K Signaling Pathways. Ann Transplant, 2018. 23: p. 1-10.
19. Reyes-Hernández, O.D., et al., 3,3′-Diindolylmethane and indole-3-carbinol: potential therapeutic molecules for cancer chemoprevention and treatment via regulating cellular signaling pathways. Cancer Cell International, 2023. 23(1): p. 180.
20. Duronio, R.J. and Y. Xiong, Signaling pathways that control cell proliferation. Cold Spring Harb Perspect Biol, 2013. 5(3): p. a008904.