Mesenchymal stem cells

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Definition

Mesenchymal stem cells, also known as mesenchymal stromal cells (MSCs), are multipotent cells of mesodermal origin, residing in many tissues of the adult organism, capable of self-renewal and differentiation both into the cells of the tissue from which they originate and into other cells of mesenchymal and non-mesenchymal origin. Mesenchymal stem / stromal cells have attracted special attention from the scientific world since their first isolation from the bone marrow by Friedenstein in the 1960s and have been described as adherent cells (adherent to the surface of plastic culture dishes) with a fibroblast-like morphology [1] [2]. However, the term mesenchymal stem cells was proposed by Caplan and introduced to denote a type of cells that originated from adult bone marrow with a natural capacity for multipotential differentiation into diverse types of cells of mesenchymal origin [3]. MSC cells are a heterogeneous population characterized by specific properties, i.e. the ability to self-renewal, the ability to differentiation into progenitor cells of a specific cell line involved in the regeneration of the damaged tissue in which they reside, and multipotency, i.e. the ability to differentiate into different types cells not only of mesodermal origin. Various types of tissue resident MSCs have been described in the literature and many reports indicate their biological features make these cells specific for the regeneration of the tissue from which they originate, however, their heterogeneity allows them to differentiate into different cell types [4]. Cells bearing the characteristics of MSCs have been isolated from many organs and tissues of the human body, including bone marrow, adipose tissue, skin, skeletal muscle, tendons, bones, liver, kidney, lung, spleen, pancreas, thymus, dental pulp, synovium and umbilical cords [5] [6] [7]. There are no specific markers to identify MSCs, however, irrespective of their tissue origin, MSCs isolated from various tissues are characterized as non-hematopoietic cells that can be identified by the presence of many common markers, including the CD29, CD44, CD73, CD90, CD105 and MHC class I antigens. MSCs do not express hematopoietic and endothelial markers on their surface, e.g. CD14, CD31, CD34, CD45, and lack of expression of MHC class II antigens and co-stimulatory molecules CD40, CD80 and CD86, permitted their non-immunogenic properties. These biological features make MSCs isolated from adult tissues a promising source of cells for developing new therapeutic strategies in regenerative medicine [8] [9] [10].

Sources of mesenchymal stem cells

  • Bone marrow: abundant in MSCs capable of differentiation into many cell types, including osteoblasts, chondrocytes, hepatocytes etc. Bone marrow-derived MSCs are an attractive material for therapeutic purposes, although their differentiation potential depends on many factors, including the age of the donor, however, a certain limitation of obtaining MSC from the bone marrow is the procedure of their collection, which is an invasive method [11] [12]
  • Adipose tissue: rich in MSCs that are highly proliferative, easily obtainable through liposuction, and capable of differentiating into cells of adipogenic, osteogenic, chondrogenic and myogenic lineages.
  • Skeletal muscle: distinct from the exclusively myogenic satellite cells, muscle-derived MSCs are capable of differentiation into cells of osteogenic and chondrogenic lineages , however, they are primarily used to repair skeletal muscle tissue. They are characterised by high self-renewal properties, and can be obtained by biopsy from any muscle of the body [13]
  • Skin: a source of highly proliferative cells, used especially for dermis regeneration, e.g. in treatment of extensive burns, but also capable of differentiation into myo-, adipo-, osteo- and chondrocytes, as well as neural and pancreatic cells. MSCs can be also isolated from hair follicles, which is probably the most easy and non-invasive way of obtaining stem cells; hair follicle MSCs can undergo adipogenesis and osteogenesis [14] [15].
  • Dental pulp: an easily accessible source of MSCs during dental surgeries. Dental pulp MSCs are usually used for bone and neural regeneration; their chondrogenic differentiation capacity is limited compared to other types of MSCs. However, some studies show a decrease in the proliferative activity of MSCs isolated from the dental pulp associated with the number of passages of cultivation time [16] [17].
  • Placenta: abundant in MSCs characterised by high proliferation rates and strong immunosuppressive effects, capable of differentiation into e.g. hepatocytes or pancreatic cells [18] [19].
  • Amniotic fluid: MSCs originating from amniotic fluid are mainly used alongside surgery as autologous material to aid organ repair in treatment of congenital birth anomalies such as spina bifida, diaphragmatic hernia or cardiac defects. Amniotic fluid is accessible by needle aspiration, and only small quantities are necessary to establish a cell culture, as they have ability to proliferate rapidly.

Bibliography

  1. ↑ Friedenstein AJ, Petrakova KV, Kurolesova AI, Frolova GP. Heterotopic of bone marrow. Analysis of precursor cells for osteogenic and hematopoietic tissues. Transplantation 1968; 6: 230-47
  2. ↑ Friedenstein A, Kuralesova AI. Osteogenic precursor cells of bone marrow in radiation chimeras. Transplantation 1971; 12: 99-108
  3. ↑ Caplan AI. Mesenchymal stem cells. J Orthop Res 1991; 9: 641-50
  4. ↑ Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S, Marshak DR. Multilineage potential of adult human mesenchymal stem cells. Science. 1999 Apr 2;284(5411):143-7. doi: 10.1126/science.284.5411.143
  5. ↑ da Silva Meirelles L, Chagastelles PC, Nardi NB. Mesenchymal stem cells reside in virtually all post-natal organs and tissues. J Cell Sci. 2006 Jun 1;119(Pt 11):2204-13. doi: 10.1242/jcs.02932. Epub 2006 May 9
  6. ↑ Klimczak A, Kozlowska U. Mesenchymal Stromal Cells and Tissue-Specific Progenitor Cells: Their Role in Tissue Homeostasis. Stem Cells Int. 2016;2016:4285215. doi: 10.1155/2016/4285215. Epub 2015 Dec 28
  7. ↑ Kozlowska U, Krawczenko A, Futoma K, Jurek T, Rorat M, Patrzalek D, Klimczak A. Similarities and differences between mesenchymal stem/progenitor cells derived from various human tissues. World J Stem Cells. 2019 Jun 26;11(6):347-374. doi: 10.4252/wjsc.v11.i6.347
  8. ↑ Pittenger MF, Discher DE, Péault BM, Phinney DG, Hare JM, Caplan AI. Mesenchymal stem cell perspective: cell biology to clinical progress. NPJ Regen Med. 2019 Dec 2;4:22. doi: 10.1038/s41536-019-0083-6
  9. ↑ Murphy MB, Moncivais K, Caplan AI. Mesenchymal stem cells: environmentally responsive therapeutics for regenerative medicine. Exp Mol Med. 2013 Nov 15;45(11):e54. doi: 10.1038/emm.2013.94
  10. ↑ Rodríguez-Fuentes DE, Fernández-Garza LE, Samia-Meza JA, Barrera-Barrera SA, Caplan AI, Barrera-Saldaña HA. Mesenchymal Stem Cells Current Clinical Applications: A Systematic Review. Arch Med Res. 2021 Jan;52(1):93-101. doi: 10.1016/j.arcmed.2020.08.006. Epub 2020 Sep 22
  11. ↑ Prockop DJ. Marrow stromal cells as stem cells for nonhematopoietic tissues. Science. 1997 Apr 4;276(5309):71-4. doi: 10.1126/science.276.5309.71
  12. ↑ Dezawa M, Ishikawa H, Itokazu Y, Yoshihara T, Hoshino M, Takeda S, Ide C, Nabeshima Y. Bone marrow stromal cells generate muscle cells and repair muscle degeneration. Science. 2005 Jul 8;309(5732):314-7. doi: 10.1126/science.1110364
  13. ↑ Klimczak A, Kozlowska U, Kurpisz M. Muscle Stem/Progenitor Cells and Mesenchymal Stem Cells of Bone Marrow Origin for Skeletal Muscle Regeneration in Muscular Dystrophies. Arch Immunol Ther Exp (Warsz). 2018 Oct;66(5):341-354. doi: 10.1007/s00005-018-0509-7. Epub 2018 Mar 13
  14. ↑ Wang B, Liu XM, Liu ZN, Wang Y, Han X, Lian AB, Mu Y, Jin MH, Liu JY. Human hair follicle-derived mesenchymal stem cells: Isolation, expansion, and differentiation. World J Stem Cells. 2020 Jun 26;12(6):462-470. doi: 10.4252/wjsc.v12.i6.462
  15. ↑ Savkovic V, Li H, Obradovic D, Masieri FF, Bartella AK, Zimmerer R, Simon JC, Etz C, Lethaus B. The Angiogenic Potential of Mesenchymal Stem Cells from the Hair Follicle Outer Root Sheath. J Clin Med. 2021 Feb 26;10(5):911. doi: 10.3390/jcm10050911
  16. ↑ Anitua E, Troya M, Zalduendo M. Progress in the use of dental pulp stem cells in regenerative medicine. Cytotherapy. 2018 Apr;20(4):479-498. doi: 10.1016/j.jcyt.2017.12.011. Epub 2018 Feb 12
  17. ↑ Alraies A, Waddington RJ, Sloan AJ, Moseley R. Evaluation of Dental Pulp Stem Cell Heterogeneity and Behaviour in 3D Type I Collagen Gels. Biomed Res Int. 2020 Sep 10;2020:3034727. doi: 10.1155/2020/3034727
  18. ↑ Wang L, Ott L, Seshareddy K, Weiss ML, Detamore MS. Musculoskeletal tissue engineering with human umbilical cord mesenchymal stromal cells. Regen Med. 2011 Jan;6(1):95-109. doi: 10.2217/rme.10.98
  19. ↑ Um S, Ha J, Choi SJ, Oh W, Jin HJ. Prospects for the therapeutic development of umbilical cord blood-derived mesenchymal stem cells. World J Stem Cells. 2020 Dec 26;12(12):1511-1528. doi: 10.4252/wjsc.v12.i12.1511
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