An overview of Mesenchymal stromal cells: biology, functional role and therapeutic potential
DOI:
https://doi.org/10.13129/1828-6550/APMB.114.1.2026.SD4Parole chiave:
Mesenchymal stromal cells (MSCs), tissue regeneration, immunomodulation, ; secretome self-renewal and differentiationAbstract
Mesenchymal stromal cells (MSCs) are multipotent non-hematopoietic cells able to auto-renewal and differentiate into mesodermal cell lineages. The cells have been attracted for their potential therapeutic roles in different diseases possessing broad spectrum of activities (immunomodulatory, trophic, anti-inflammatory and migratory). Thus, MSCs represent optimal biological “tool" for tissue regeneration approaches both in human and animals. MSCs firstly isolated from bone marrow (BM) (Friedenstein, 1970) can be obtained from different sources and organs in adults like, adipose tissue (AT), Wharton’s jelly, dental pulp, peripheral blood, etc. Upon isolation, MSCs can be characterized by their ability to grow and expand on plastic plates and can differentiate into multiple lineages like osteocytes, chondrocytes, myocytes, adipocytes, and express certain cell surface markers like cluster of differentiation (CD) CD90, CD105, CD73 and are negative for markers like CD45, CD34, CD14, CD11b, CD19. In addition, they express low level of major histocompatibility complex (MHC) class I, CD40, CD80, CD86 and do not express MHC class II molecules, which make these cells immune privileged and an ideal candidate for allogenic transplantation in diseased patients.
Recent studies demonstrating the reduced MSCs engraftment revealed that their beneficial regenerative effects primarily derive from paracrine activity (secretome release) rather than differentiation capacity.
Today, MSCs are at the forefront of regenerative medicine, offering potential treatments for a wide range of diseases (in primis musculo-skeletal, neurodegenerative and auto-immune) for which MSCs act by reducing inflammation and pain, and promoting the development of hyaline cartilage.
Future research is directed towards new and important objectives (optimization of MSC sources and dosage, use of MSC exosomes and/or in combination with other substances/cells) that can allow us to enhance knowledge and increase the number of clinical studies.
Riferimenti bibliografici
1. Friedenstein, A.J., Chailakhjan, R.K., Lalykina, K.S. (1970). The development of fibroblast colonies in monolayer cultures of guinea‑pig bone marrow and spleen cells. Cell Tissue Kinet, 3, 393‑403. doi: 10.1111/j.1365-2184.1970.tb00347.x.
2. Dominici, M., Le Blanc, K., Mueller, I., Slaper‑Cortenbach, I., Marini, F., Krause, D., Deans, R., Keating, A., Prockop, D., Horwitz, E. (2006). Minimal criteria for defining multipotent mesenchymal stromal cells. The international society for cellular therapy position statement. Cytotherapy, 8, 315‑317. doi: 10.1080/14653240600855905.
3. Păunescu, V., Deak, E., Herman, D., Siska, I.R., Tănasie, G., Bunu, C., Anghel, S., Tatu, C.A., Oprea, T.I., Henschler, R., Rüster, B., Bistrian, R., Seifriedet, E. (2007). In vitro differentiation of human mesenchymal stem cells to epithelial lineage. J Cell Mol Med, 11, 502‑508. doi: 10.1111/j.1582-4934.2007.00041.x.
4. Yang. Y.H.K. (2018) Aging of mesenchymal stem cells: Implication in regenerative medicine. Regen Ther, 9, 120‑122. doi: 10.1016/j.reth.2018.09.002. eCollection 2018 Dec.
5. Chen, J.Y., Mou, X.Z., Du, X.C., Xiang, C. (2015). Comparative analysis of biological characteristics of adult mesenchymal stem cells with different tissue origins. Asian Pac J Trop Med, 8, 739–746. doi: 10.1016/j.apjtm.2015.07.022. Epub 2015 Jul 29.
6. Kwon, A., Kim, Y., Kim, M., Kim, J., Choi, H., Jekarl, W.D., Lee, S., Kim, J.M., Shin, J.C., Park, I.N. (2016). Tissue-specific differentiation potency of mesenchymal stromal cells from perinatal tissues. Sci Rep, 6, 23544. doi: 10.1038/srep23544.
7. Dominici, M., Le Blanc, K., Mueller, I., Slaper-Cortenbach, I., Marini, F., Krause, D., Deans, R., Keating, A., Prockop, D., Horwitz, E. (2006). Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy, 8, 315e7. doi: 10.1080/14653240600855905.
8. Boxall, S.A., Jones, E. (2012). Markers for characterization of bone marrow multipotential stromal cells. Stem Cell Int, 2012, 975871. doi: 10.1155/2012/975871.975871.
9. Fu, X., Liu, G., Halim, A., Ju, Y., Luo, Q., Song, G. (2019). Mesenchymal stem cell migration and tissue repair. Cells, 8, 784. doi: 10.3390/cells8080784.
10. Zannetti, A., Benga, G., Brunetti, A., Napolitano, F., Avallone, L., Pelagalli, A. (2020). Role of aquaporins in the physiological functions of mesenchymal stem cells. Cells, 9, 2678. doi: 10.3390/cells9122678.
11. Zachar, L., Bačenková, D., Rosocha, J. (2016). Activation, homing, and role of the mesenchymal stem cells in the inflammatory environment. J Inflamm Res, 9, 231-240. doi: 10.2147/JIR.S121994. eCollection 2016.
12. Regulski, M.J. (2017). Mesenchymal stem cells: “guardians of inflammation.” Wounds, 29, 20-27.
Krampera, M. (2011). Mesenchymal stromal cell 'licensing': a multistep process. Leukemia, 25, 1408-1414. doi: 10.1038/leu.2011.108. Epub 2011 May 27.
13. Spees, J.L., Lee, R.H., Gregory. C.A. (2016) Mechanisms of mesenchymal stem/stromal cell function. Stem Cell Res Therap, 7, 125. doi: 10.1186/s13287-016-0363-7.
14. Saba, E., Sandhu, M.A., Pelagalli, A. (2024). Canine mesenchymal stromal cell exosomes: state-of-the-art characterization, functional analysis and applications in various diseases. Vet Sci, 11, 187. doi: 10.3390/vetsci11050187.
15. Pelagalli, A., Nardelli, A., Lucarelli, E., Zannetti, A., Brunetti, A. (2018). Autocrine signals increase ovine mesenchymal stem cells migration through Aquaporin-1 and CXCR4 overexpression. J Cell Physiol, 233, 6241-6249. doi: 10.1002/jcp.26493. Epub 2018 Mar 1.
16. Sun, H., Zhai, H., Han, K., Ma, H., Tan, Y., Li, S., Liu, Z., Cheng, L., Lu, Q., Zhou, L., Liu, P. (2024). Clinical outcomes of autologous adipose-derived mesenchymal stem cell combined with high tibial osteotomy for knee osteoarthritis are correlated with stem cell stemness and senescence. J Transl Med, 22, 1039. doi: 10.1186/s12967-024-05814-3.
17. Vonk, L.A., van Dooremalen, S.F.J., Liv, N., Klumperman, J., Coffer, P.J., Saris, D.B.F., Lorenowicz, M.J. (2018). Mesenchymal stromal/stem cell-derived extracellular vesicles promote human cartilage regeneration in vitro. Theranostics, 8, 906-920 (2018). doi: 10.7150/thno.20746. eCollection 2018.
18. Brondeel, C., Pauwelyn, G., de Bakker, E., Saunders, J., Samoy, Y., Spaas, J.H. (2021). Review: Mesenchymal Stem Cell Therapy in Canine Osteoarthritis Research: “Experientia Docet” (Experience Will Teach Us). Front Vet Sci, 8, 668881. doi: 10.3389/fvets.2021.668881. eCollection 2021.
19. Shi, W., Xin, Q., Yuan, R., Yuan, Y., Cong, W., Chen, K. (2021). Neovascularization: The main mechanism of MSCs in ischemic heart disease therapy. Front Cardiovasc Med, 8, 633300. doi: 10.3389/fcvm.2021.633300.
20. Bagno, L., Hatzistergos, K.E., Balkan, W., Hare, J.M. (2018). Mesenchymal stem cell-based therapy for cardiovascular disease: progress and challenges. Mol Ther 25, 26, 1610-1623. doi: 10.1016/j.ymthe.2018.05.009.
21. Fernandez-Aviles, F., Sanz-Ruiz, R., Climent, A.M., Badimon, L., Bolli, R., Charron, D., Fuster, V., Janssens, S., Kastrup, J., Kim, H.S., Lüscher, T.F., Martin, J.F., Menasché, P., Simari, R.D., Stone, G.W.,e Terzic, A., Willerson, J.T., Wu, J.C. (2017). Global position paper on cardiovascular regenerative medicine. Eur Heart J, 38, 2532-2546. doi: 10.1093/eurheartj/ehx248.
22. Sadatpoor, S.O., Salehi, Z., Rahban, D., Salimi, A. (2021). Manipulated mesenchymal stem cells applications in neurodegenerative diseases. Int J Stem Cells, 13, 24-45. doi: 10.15283/ijsc19031.
23. Paul, G., Anisimov, S.V. (2013). The secretome of mesenchymal stem cells: potential implications for neuroregeneration. Biochimie, 95, 2246-2256. doi: 10.1016/j.biochi.2013. 07.013
24. Abdelrazik, H., Pelagalli, A. (2023). Novel MSC Perspectives: From cell regulation to tissue regeneration. Int J Mol Sci, 24, 13392. doi: 10.3390/ijms241713392.
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