1. Please check and comment entries here.
Table of Contents

    Topic review

    Mesenchymal stromal cells (MSCs)

    View times: 149
    Submitted by: Ludmila Buravkova

    Definition

    Mesenchymal stem cells (MSCs) are a heterogeneous population of  stromal precursors with high proliferative activity and multilineage differentiation, which keeps them in demand for clinical use. The MSC secretome affects the microenvironment promoting cytoprotection and tissue repair. Adipose tissue is one of the most perspective sources of MSCs since they can be obtained in sufficient amounts from patients using a minimally invasive procedure. With aging, the regenerative capabilities of the tissues that are largely due to the activity of adult stem cells are decreased. Due to their tissue niche role of maintaining homeostasis and auto-/paracrine regulation, MSCs are especially interesting from the point of view of cell senescence.  Senescence‐associated secretory phenotype (SASP) is the most important cause of disturbance of cell communication, which leads to various consequences in the surrounding tissues during aging. 

    1. Introduction

    Mesenchymal stromal cells (MSCs) are a heterogeneous population of poorly differentiated stromal precursors with high proliferative activity and multilineage differentiation, which keeps them in demand for clinical use [1][2]. These days, the positive effects of MSCs are mainly attributed to their ability to produce a number of biologically active factors, including cytokines, exosomes, and extracellular matrix components [3][4][5][6]. The MSC secretome affects the microenvironment at damage area, promoting cytoprotection and tissue repair. These effects are of particular interest for the treatment of ischemia, where the stimulation of vascularization is crucial for the preservation of alive tissue and, therefore, for the prevention of fibrosis [7].

    However, the properties of the cell population can vary significantly depending on the donor, tissue sources, and even individual cell clones. This fact complicates the comparison of the results and necessitates the study of each tissue-specific population separately [8]. Adipose tissue is one of the most perspective sources of MSCs since they can be obtained in sufficient amounts from patients using a minimally invasive procedure. Adipose-derived MSCs (ASCs) are considered a promising tool for various types of cell therapy and tissue engineering[9]. According to several authors, ASCs have some advantages over the bone marrow MSCs, including a greater number of precursors from the similar amount of the sample and an increased capability of proliferation, differentiation, and angiogenesis in vivo [10][11][12]. Application of ASCs resulted to increase in the number of vessels and blood flow restoration in damaged tissues after the limb ischemia [13][14][15] and myocardial infarction [16][17]. Neovascularization after administration of ASCs or conditioned medium (CM) was considered the main mechanisms of hepatic regeneration [18].

    2. Conclusion

    Due to their tissue niche role of maintaining homeostasis and auto-/paracrine regulation, MSCs are especially interesting from the point of view of cell senescence. With the activation of senescence, MSCs change their morphofunctional state. Irreversible arrest of the cell cycle occurs, the morphology, organelles activity, and gene expression are altered, γH2AX heterochromatin foci appear, and a number of other cell senescence markers are found. Senescent cells are able to maintain their viability and functional activity for a rather long period, continuing to interact with the microenvironment and providing local and systemic effects [19][20][21][22][23].

    This entry is adapted from 10.3390/ijms21051802

    References

    1. Pittenger, M.F.; Mackay, A.M.; Beck, S.C.; Jaiswal, R.K.; Douglas, R.; Mosca, J.D.; Marshak, D.R. Multilineage potential of adult human mesenchymal stem cells. Science 1999, 284, 143–147. [Google Scholar] [CrossRef] [PubMed]
    2. Horwitz, E.M.; Le Blanc, K.; Dominici, M.; Mueller, I.; Slaper-Cortenbach, I.; Marini, F.C.; Keating, A. Clarification of the nomenclature for MSC: The International Society for Cellular Therapy position statement. Cytotherapy 2005, 7, 393–395. [Google Scholar] [CrossRef] [PubMed]
    3. Baraniak, P.R.; McDevitt, T.C. Stem cell paracrine actions and tissue regeneration. Regen. Med. 2010, 5, 121–143. [Google Scholar] [CrossRef] [PubMed]
    4. Murphy, M.B.; Moncivais, K.; Caplan, A.I. Mesenchymal stem cells: Environmentally responsive therapeutics for regenerative medicine. Exp. Mol. Med. 2013, 45, 54. [Google Scholar] [CrossRef]
    5. Lunyak, V.V.; Amaro-Ortiz, A.; Gaur, M. Mesenchymal stem cells secretory responses: Senescence messaging secretome and immunomodulation perspective. Front. Genet. 2017, 8, 220. [Google Scholar] [CrossRef]
    6. Bellin, G.; Gardin, C.; Ferroni, L.; Chachques, J.C.; Rogante, M.; Mitrečić, D.; Ferrari, R.; Zavan, B. Exosome in cardiovascular diseases: A complex world full of hope. Cells 2019, 8, 166. [Google Scholar] [CrossRef]
    7. Kehl, D.; Generali, M.; Mallone, A.; Heller, M.; Uldry, A.C.; Cheng, P.; Gantenbein, B.; Hoerstrup, S.P.; Weber, B. Proteomic analysis of human mesenchymal stromal cell secretomes: A systematic comparison of the angiogenic potential. NPJ Regen. Med. 2019, 4, 1–3. [Google Scholar] [CrossRef]
    8. McLeod, C.M.; Mauck, R.L. On the origin and impact of mesenchymal stem cell heterogeneity: New insights and emerging tools for single cell analysis. Eur. Cell Mater. 2017, 34, 217–231. [Google Scholar] [CrossRef]
    9. Schäffler, A.; Büchler, C. Concise review: Adipose tissue-derived stromal cells—Basic and clinical implications for novel cell-based therapies. Stem Cells 2007, 25, 818–827. [Google Scholar] [CrossRef]
    10. Kim, Y.J.; Kim, H.K.; Cho, H.H.; Bae, Y.C.; Suh, K.T.; Jung, J.S. Direct comparison of human mesenchymal stem cells derived from adipose tissues and bone marrow in mediating neovascularization in response to vascular ischemia. Cell. Physiol. Biochem. 2007, 20, 867–876. [Google Scholar] [CrossRef]
    11. Barba, M.; Cicione, C.; Bernardini, C.; Michetti, F.; Lattanzi, W. Adipose-derived mesenchymal cells for bone regereneration: State of the art. BioMed Res. Int. 2013, 2013. [Google Scholar] [CrossRef] [PubMed]
    12. Dufrane, D. Impact of age on human adipose stem cells for bone tissue engineering. Cell Transplant. 2017, 26, 1496–1504. [Google Scholar] [CrossRef] [PubMed]
    13. Moon, M.H.; Kim, S.Y.; Kim, Y.J.; Kim, S.J.; Lee, J.B.; Bae, Y.C.; Sung, S.M.; Jung, J.S. Human adipose tissue-derived mesenchymal stem cells improve postnatal neovascularization in a mouse model of hindlimb ischemia. Cell Physiol. Biochem. 2006, 17, 279–290. [Google Scholar] [CrossRef] [PubMed]
    14. Gimble, J.M.; Katz, A.J.; Bunnell, B.A. Adipose-derived stem cells for regenerative medicine. Circ. Res. 2007, 100, 1249–1260. [Google Scholar] [CrossRef]
    15. Kondo, K.; Shintani, S.; Shibata, R.; Murakami, H.; Murakami, R.; Imaizumi, M.; Kitagawa, Y.; Murohara, T. Implantation of adipose-derived regenerative cells enhances ischemia-induced angiogenesis. Arterioscler. Thromb. Vasc. Biol. 2009, 29, 61–66. [Google Scholar] [CrossRef]
    16. Miyahara, Y.; Nagaya, N.; Kataoka, M.; Yanagawa, B.; Tanaka, K.; Hao, H.; Ishino, K.; Ishida, H.; Shimizu, T.; Kangawa, K.; et al. Monolayered mesenchymal stem cells repair scarred myocardium after myocardial infarction. Nat. Med. 2006, 12, 459–465. [Google Scholar] [CrossRef]
    17. Madonna, R.; De Caterina, R. Adipose tissue: A new source for cardiovascular repair. J. Cardiovasc. Med. 2010, 11, 71–80. [Google Scholar] [CrossRef]
    18. Nahar, S.; Nakashima, Y.; Miyagi-Shiohira, C.; Kinjo, T.; Toyoda, Z.; Kobayashi, N.; Saitoh, I.; Watanabe, M.; Noguchi, H.; Fujita, J. Cytokines in adipose-derived mesenchymal stem cells promote the healing of liver disease. World J. Stem Cells 2018, 10, 146. [Google Scholar] [CrossRef]
    19. Turinetto, V.; Vitale, E.; Giachino, C. Senescence in human mesenchymal stem cells: Functional changes and implications in stem cell-based therapy. Int. J. Mol. Sci. 2016, 17, 1164. [Google Scholar] [CrossRef]
    20. Li, Y.; Wu, Q.; Wang, Y.; Li, L.; Bu, H.; Bao, J. Senescence of mesenchymal stem cells. Int. J. Mol. Med. 2017, 39, 775–782. [Google Scholar] [CrossRef]
    21. Gu, Y.; Li, T.; Ding, Y.; Sun, L.; Tu, T.; Zhu, W.; Hu, J.; Sun, X. Changes in mesenchymal stem cells following long-term culture in vitro. Mol. Med. Rep. 2016, 13, 5207–5215. [Google Scholar] [CrossRef] [PubMed]
    22. Legzdina, D.; Romanausk, A.; Nikulshin, S.; Kozlovska, T.; Berzins, U. Characterization of senescence of culture-expanded human adipose-derived mesenchymal stem cells. Int. J. Stem Cells 2016, 9, 124. [Google Scholar] [CrossRef] [PubMed]
    23. Ratushnyy, A.; Lobanova, M.; Buravkova, L.B. Expansion of adipose tissue-derived stromal cells at “physiologic” hypoxia attenuates replicative senescence. Cell Biochem. Funct. 2017, 35, 232–243. [Google Scholar] [CrossRef] [PubMed]
    More