Mesenchymal stromal cells (MSCs): Comparison
Please note this is a comparison between Version 2 by Bruce Ren and Version 1 by Ludmila Buravkova.

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. 

  • adipose-derived mesenchymal stem cells
  • replicative senescence
  • senescenceassociated secretory phenotype (SASP)

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 [

,

]. 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 [

,

,

,

]. 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 [

].

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 [

]. 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 [

]. 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 [

,

,

]. Application of ASCs resulted to increase in the number of vessels and blood flow restoration in damaged tissues after the limb ischemia [

,

,

] and myocardial infarction [

,

]. Neovascularization after administration of ASCs or conditioned medium (CM) was considered the main mechanisms of hepatic regeneration [

].

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 [

,

,

,

,

].

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, doi:10.1126/science.284.5411.143.

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, doi:10.1080/14653240500319234.

3. Baraniak, P.R.; McDevitt, T.C. Stem cell paracrine actions and tissue regeneration. Regen. Med. 2010, 5, 121–143, doi:10.2217/rme.09.74.

4. Murphy, M.B.; Moncivais, K.; Caplan, A.I. Mesenchymal stem cells: Environmentally responsive therapeutics for regenerative medicine. Exp. Mol. Med. 2013, 45, 54–54, doi:10.1038/emm.2013.94.

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, doi:10.3389/fgene.2017.00220.

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, doi:10.3390/cells8020166.

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, doi:10.1038/s41536‐019‐0070‐y.

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, doi:10.22203/eCM.v034a14.

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, doi:10.1634/stemcells.2006‐0589.

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, doi:10.1159/000110447.

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, doi:10.1155/2013/416391.
12. Dufrane, D. Impact of age on human adipose stem cells for bone tissue engineering. Cell Transplant. 2017,26, 1496–1504, doi:10.1155/2013/416391.

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, doi:10.1159/000094140.

14. Gimble, J.M.; Katz, A.J.; Bunnell, B.A. Adipose‐derived stem cells for regenerative medicine. Circ. Res. 2007,100, 1249–1260, doi:10.1161/01.

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, doi:10.1161/ATVBAHA.108.166496.

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, doi:10.1038/nm1391.

17. Madonna, R.; De Caterina, R. Adipose tissue: A new source for cardiovascular repair. J. Cardiovasc. Med. 2010, 11, 71–80, doi:10.2459/JCM.0b013e328330e9be.

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, doi:10.4252/wjsc.v10.i11.146.

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, doi:10.3390/ijms17071164.

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, doi:10.3892/ijmm.2017.2912.

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, doi:10.3892/mmr.2016.5169.

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, doi:10.15283/ijsc.2016.9.1.124.

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, doi:10.1002/cbf.3267.