Highlights
• Establishment of a rapid and high-quality culture platform for hMenSCs & endometrial organoids
• Gene network regulated by FGF2 in hMenSCs & endometrial organoids
• The divergent effects of FGF2 on hMenSCs & endometrial organoids
Discover the SciOpen Platform and Achieve Your Research Goals with Ease.
Search articles, authors, keywords, DOl and etc.
• Establishment of a rapid and high-quality culture platform for hMenSCs & endometrial organoids
• Gene network regulated by FGF2 in hMenSCs & endometrial organoids
• The divergent effects of FGF2 on hMenSCs & endometrial organoids
Human menstrual blood-derived stem cells (hMenSCs) show promise in regenerative medicine and endometrial disease treatments. Organoids, three-dimensional (3D) tissue replicas, provide accurate disease models. Fibroblast growth factor 2 (FGF2), with established roles in stem cell functions, remains underexplored in its impact on hMenSCs and endometrial organoids. Our study aims to explore these unexplored effects of FGF2. In our study, we have developed a method for rapid and high-quality cultivation of MenSCs and organoids. Using this novel platform, we demonstrate that FGF2 alters hMenSC morphology, enhancing growth and proliferative, migratory, and anti-aging capabilities. RNA sequencing suggests this is linked to downregulated cell adhesion genes. FGF2 promotes proliferation via ribosomal biogenesis and ATP metabolism, possibly delaying senescence. In organoids, FGF2 reverses compaction and volume reduction, promoting growth and fibroblast release. q-PCR analysis shows FGF2 regulates genes related to stemness, proliferation, metabolism, and PI3K-AKT signaling, with distinct patterns in hMenSCs and organoids. This research advances regenerative medicine and reproductive biology by optimizing the cultivation of hMenSCs and organoids with FGF2 for potential therapeutic applications.
Zhou,T., Yuan, Z. N., Weng, J. Y., Pei, D. Q., Du, X., He, C., Lai, P. L. Challenges and advances in clinical applications of mesenchymal stromal cells. Journal of Hematology & Oncology, 2021, 14: 24. https://doi.org/10.1186/s13045-021-01037-x
Zheng, Sheng-Xia, Wang, J., Wang, Xue-Li, Ali, A., Wu, Li-Min, Liu, Yu-Sheng. Feasibility analysis of treating severe intrauterine adhesions by transplanting menstrual blood-derived stem cells. International Journal of Molecular Medicine, 2018, 41(4): 2201–2212. https://doi.org/10.3892/ijmm.2018.3415
Khoury, M., Alcayaga-Miranda, F., Illanes, S. E., Figueroa, F. E. The promising potential of menstrual stem cells for antenatal diagnosis and cell therapy. Frontiers in Immunology, 2014, 5: 205. https://doi.org/10.3389/fimmu.2014.00205
Wu, M. J., Wu, S. N., Tan, S. D., Xu, Q. X., Zhang, D. H., Sun, J. X., Yang, H. Y., Wang, C. C., Duan, T., Xu, Y. et al. VitroGel-loaded human MenSCs promote endometrial regeneration and fertility restoration. Frontiers in Bioengineering and Biotechnology, 2024, 11: 1310149. https://doi.org/10.3389/fbioe.2023.1310149
Jiang, Z., Hu, X. Y., Yu, H., Xu, Y. C., Wang, L. H., Chen, H., Chen, H. Q., Wu, R. R., Zhang, Z. C., Xiang, C. S. et al. Human endometrial stem cells confer enhanced myocardial salvage and regeneration by paracrine mechanisms. Journal of Cellular and Molecular Medicine, 2013, 17(10): 1247–1260. https://doi.org/10.1111/jcmm.12100
Wu, X. X., Luo, Y. Q., Chen, J. Y., Pan, R. L., Xiang, B. Y., Du, X. C., Xiang, L. X., Shao, J. Z., Xiang, C. Transplantation of human menstrual blood progenitor cells improves hyperglycemia by promoting endogenous progenitor differentiation in type 1 diabetic mice. Stem Cells and Development, 2014, 23(11): 1245–1257. https://doi.org/10.1089/scd.2013.0390
Chen, L. J., Zhang, C. F., Chen, L., Wang, X. J., Xiang, B. Y., Wu, X. X., Guo, Y., Mou, X. Z., Yuan, L., Chen, B. et al. Human menstrual blood-derived stem cells ameliorate liver fibrosis in mice by targeting hepatic stellate cells via paracrine mediators. Stem Cells Translational Medicine, 2017, 6(1): 272–284. https://doi.org/10.5966/sctm.2015-0265
Savchenko, E., Teku, G. N., Boza-Serrano, A., Russ, K., Berns, M., Deierbong, T., Lamas, N. J., Wichterle, H., Rothstein, J., Henderson, C. E., et al. FGF family members differentially regulate maturation and proliferation of stem cell-derived astrocytes. Scientific Reports, 2019, 9(1): 9610. https://doi.org/10.1038/s41598-019-46110-1
Schmidt, A., Ladage, D., Schinköthe, T., Klausmann, U., Ulrichs, C., Klinz, F. J., Brixius, K., Arnhold, S., Desai, B. R., Mehlhorn, U. et al. Basic fibroblast growth factor controls migration in human mesenchymal stem cells. Stem Cells, 2006, 24(7): 1750–1758. https://doi.org/10.1634/stemcells.2005-0191
Liu, K. Y., Yu, S. J., Ye, L., Gao, B. The regenerative potential of bFGF in dental pulp repair and regeneration. Frontiers in Pharmacology, 2021, 12: 680209. https://doi.org/10.3389/fphar.2021.680209
Georg Magalhães, C., Ploeger Mansueli, C., Manieri, T. M., Quintilio, W., Garbuio, A., de Jesus Marinho, J., de Moraes, J. Z., Tsuruta, L. R., Moro, A. M. Impaired proliferation and migration of HUVEC and melanoma cells by human anti-FGF2 mAbs derived from a murine hybridoma by guided selection. Bioengineered, 2023, 14(1): 2252667. https://doi.org/10.1080/21655979.2023.2252667
Howard, C., Murray, P. E., Namerow, K. N. Dental pulp stem cell migration. Journal of Endodontics, 2010, 36(12): 1963–1966. https://doi.org/10.1016/j.joen.2010.08.046
Turner, C., Watson, S., Akil, H. The fibroblast growth factor family: Neuromodulation of affective behavior. Neuron, 2012, 76(1): 160–174. https://doi.org/10.1016/j.neuron.2012.08.037
Diecke, S., Quiroga-Negreira, A., Redmer, T., Besser, D. FGF2 signaling in mouse embryonic fibroblasts is crucial for self-renewal of embryonic stem cells. Cells Tissues Organs, 2008, 188(1–2): 52–61. https://doi.org/10.1159/000121282
Chen, L. J., Qu, J. J., Xiang, C. The multi-functional roles of menstrual blood-derived stem cells in regenerative medicine. Stem Cell Research & Therapy, 2019, 10(1): 1. https://doi.org/10.1186/s13287-018-1105-9
Wu, J. Y., Huang, G. T. J., He, W. X., Wang, P., Tong, Z. C., Jia, Q., Dong, L. P., Niu, Z. Y., Ni, L. X. Basic fibroblast growth factor enhances stemness of human stem cells from the apical papilla. Journal of Endodontics, 2012, 38(5): 614–622. https://doi.org/10.1016/j.joen.2012.01.014
Han, X.-X., Jin, S. K., Yu, L. M., Wang, M., Hu, X. H., Hu, D. Y., Ren, J., Zhang, M., Huang, W., Deng, J. J. et al. Interferon-beta inhibits human glioma stem cell growth by modulating immune response and cell cycle related signaling pathways. Cell Regeneration, 2022, 11(1): 23. https://doi.org/10.1186/s13619-022-00123-w
Moskwa, N., Mahmood, A., Nelson, D. A., Altrieth, A. L., Forni, P. E., Larsen, M. Single-cell RNA sequencing reveals PDGFRα+ stromal cell subpopulations that promote proacinar cell differentiation in embryonic salivary gland organoids. Development, 2022, 149(6): dev200167. https://doi.org/10.1242/dev.200167
Huang, Y. C., Chen, W. C., Yu, C. L., Chang, T. K., I-Chin Wei, A., Chang, T. M., Liu, J. F., Wang, S. W. FGF2 drives osteosarcoma metastasis through activating FGFR1-4 receptor pathway-mediated ICAM-1 expression. Biochemical Pharmacology, 2023, 218: 115853. https://doi.org/10.1016/j.bcp.2023.115853
Chen, K. Y., Rao, Z. H., Dong, S. Y., Chen, Y. J., Wang, X. L., Luo, Y. D., Gong, F. H., Li, X. K. Roles of the fibroblast growth factor signal transduction system in tissue injury repair. Burns & Trauma, 2022, 10: tkac005. https://doi.org/10.1093/burnst/tkac005
Leung, K. T., Chan, K. Y. Y., Ng, P. C., Lau, T. K., Chiu, W. M., Tsang, K. S., Li, C. K., Kong, C. K. L., Li, K. R. The tetraspanin CD9 regulates migration, adhesion, and homing of human cord blood CD34+ hematopoietic stem and progenitor cells. Blood, 2011, 117(6): 1840–1850. https://doi.org/10.1182/blood-2010-04-281329
Hemler, M. E. Tetraspanin proteins promote multiple cancer stages. Nature Reviews Cancer, 2014, 14(1): 49–60. https://doi.org/10.1038/nrc3640
Levy, S., Shoham, T. The tetraspanin web modulates immune-signalling complexes. Nature Reviews Immunology, 2005, 5(2): 136–148. https://doi.org/10.1038/nri1548
Pan, G. J., Thomson, J. A. Nanog and transcriptional networks in embryonic stem cell pluripotency. Cell Research, 2007, 17(1): 42–49. https://doi.org/10.1038/sj.cr.7310125
Cheng, Y., Lin, K. H., Young, T. H., Cheng, N. C. The influence of fibroblast growth factor 2 on the senescence of human adipose-derived mesenchymal stem cells during long-term culture. Stem Cells Translational Medicine, 2020, 9(4): 518–530. https://doi.org/10.1002/sctm.19-0234
Coutu, D. L., Galipeau, J. Roles of FGF signaling in stem cell self-renewal, senescence and aging. Aging, 2011, 3(10): 920–933. https://doi.org/10.18632/aging.100369
Levenstein, M. E., Ludwig, T. E., Xu, R. H., Llanas, R. A., VanDenHeuvel-Kramer, K., Manning, D., Thomson, J. A. Basic fibroblast growth factor support of human embryonic stem cell self-renewal. Stem Cells, 2006, 24(3): 568–574. https://doi.org/10.1634/stemcells.2005-0247
Glazier, D. S. How metabolic rate relates to cell size. Biology, 2022, 11(8): 1106. https://doi.org/10.3390/biology11081106
Gong, J. X., Nirala, N. K., Chen, J. Z., Wang, F., Gu, P. Y., Wen, Q., Ip, Y. T., Xiang, Y. TrpA1 is a shear stress mechanosensing channel regulating intestinal stem cell proliferation in Drosophila. Science Advances, 2023, 9(21): eadc9660. https://doi.org/10.1126/sciadv.adc9660
Low, S., Barnes, J. L., Zammit, P. S., Beauchamp, J. R. Delta-like 4 activates Notch 3 to regulate self-renewal in skeletal muscle stem cells. Stem Cells, 2018, 36(3): 458–466. https://doi.org/10.1002/stem.2757
Lv, K. S., Gong, C. J., Antony, C., Han, X., Ren, J. G., Donaghy, R., Cheng, Y., Pellegrino, S., Warren, A. J., Paralkar, V. R. et al. HectD1 controls hematopoietic stem cell regeneration by coordinating ribosome assembly and protein synthesis. Cell Stem Cell, 2021, 28(7): 1275–1290.e9. https://doi.org/10.1016/j.stem.2021.02.008
Xue, M. L., Dong, L., Zhang, H. H., Li, Y. C., Qiu, K. Q., Zhao, Z. C., Gao, M., Han, L., Chan, A. K. N., Li, W. et al. METTL16 promotes liver cancer stem cell self-renewal via controlling ribosome biogenesis and mRNA translation. Journal of Hematology & Oncology, 2024, 17(1): 7. https://doi.org/10.1186/s13045-024-01526-9
Nourshargh, S., Alon, R. Leukocyte migration into inflamed tissues. Immunity, 2014, 41(5): 694–707. https://doi.org/10.1016/j.immuni.2014.10.008
Mishra, Y. G., Manavathi, B. Focal adhesion dynamics in cellular function and disease. Cellular Signalling, 2021, 85: 110046. https://doi.org/10.1016/j.cellsig.2021.110046
Mossahebi-Mohammadi, M., Quan, M. Y., Zhang, J. S., Li, X. K. FGF signaling pathway: A key regulator of stem cell pluripotency. Frontiers in Cell and Developmental Biology, 2020, 8: 79. https://doi.org/10.3389/fcell.2020.00079
Seo, B. J., Choi, J., La, H., Habib, O., Choi, Y., Hong, K., Do, J. T. Role of mitochondrial fission-related genes in mitochondrial morphology and energy metabolism in mouse embryonic stem cells. Redox Biology, 2020, 36: 101599. https://doi.org/10.1016/j.redox.2020.101599
Fumarola, C., Cretella, D., La Monica, S., Bonelli, M. A., Alfieri, R., Caffarra, C., Quaini, F., Madeddu, D., Falco, A., Cavazzoni, A. et al. Enhancement of the anti-tumor activity of FGFR1 inhibition in squamous cell lung cancer by targeting downstream signaling involved in glucose metabolism. Oncotarget, 2017, 8(54): 91841–91859. https://doi.org/10.18632/oncotarget.19279
Tobias, I. C., Isaac, R. R., Dierolf, J. G., Khazaee, R., Cumming, R. C., Betts, D. H. Metabolic plasticity during transition to naïve-like pluripotency in canine embryo-derived stem cells. Stem Cell Research, 2018, 30: 22–33. https://doi.org/10.1016/j.scr.2018.05.005
The articles published in this open access journal are distributed under the termsof the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits use, distribution andreproduction in any medium, provided the original work is properly cited.