Skip to main content
PMC home page
Science Progress logoLink to Science Progress
. 2010 Jun 2;93(2):113–127. doi: 10.3184/003685010X12708175591515

Biology and applications of Mesenchymal Stem Cells

Pedro Cesar Chagasteeles 1, Nance Beyer Nardi 1, Melissa Camassola 1,*
PMCID: PMC10365478  PMID: 20681317

Abstract

Undifferentiated adult stem cells are responsible for cell replacement in adult organisms. Initially isolated from the bone marrow, they are now known to be distributed throughout the organism as a whole, with a perivascular location. They are defined by properties which include proliferation as adherent cells, a defined immunophenotype, and the capacity to differentiate in vitro into osteoblasts, adipocytes and chondroblasts. Mesenchymal stem cells (MSCs) are considered as one of the most promising cell types for therapeutic applications. Mechanisms responsible for this therapeutic role are not well understood, and may involve differentiation or, as most evidences point out, paracrine activity. The ability to modulate the immune system opens a wide range of applications, mainly for autoimmune diseases and graft-versus-host disease. Preclinical and clinical studies show promising results, but controversial results are still reported, indicating the need for further basic and preclinical investigation on their therapeutic potential. This review will focus on recent advances in understanding MSC biology and applications in cell therapy.

Keywords: mesenchymal stem cells, adult stem cells, cell therapy, biology, applications

Full Text

The Full Text of this article is available as a PDF (785.2 KB).

References

  • 1.Morrison S.J., and Spradling A.C. (2008) Stem cells and niches: mechanisms that promote stem cell maintenance throughout life. Cell, 132, 598–611. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.da Silva Meirelles L., Chagastelles P.C., and Nardi N.B. (2006) Mesenchymal stem cells reside in virtually all post-natal organs and tissues. J. Cell Sci., 119, 2204–2213. [DOI] [PubMed] [Google Scholar]
  • 3.Huang A.H., Snyder B.R., Cheng P.H., and Chan A.W. (2008) Putative dental pulp-derived stem/stromal cells promote proliferation and differentiation of endogenous neural cells in the hippocampus of mice. Stem Cells, 26, 2654–2663. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4.Mitchell J.B., McIntosh K., Zvonic S., Garrett S., Floyd Z.E., Kloster A., Halvorsen Y.D., Storms R.W., Goh B., Kilroy G., Wu X., and Gimble J.M. (2006) Immunophenotype of human adipose- derived cells: temporal changes in stromal-associated and stem cell-associated markers. Stem Cells, 24, 376–385. [DOI] [PubMed] [Google Scholar]
  • 5.Huang X., Cho S., and Spangrude G.J. (2007) Hematopoietic stem cells: generation and self-renewal. Cell Death Differ., 14, 1851–1859. [DOI] [PubMed] [Google Scholar]
  • 6.Gaudio E., Carpino G., Cardinale V., Franchitto A., Onori P., and Alvaro D. (2009) New insights into liver stem cells. Dig. Liver Dis., 41, 455–462. [DOI] [PubMed] [Google Scholar]
  • 7.Suzuki A., Nakauchi H., and Taniguchi H. (2004) Prospective isolation of multipotent pancreatic progenitors using flow-cytometric cell sorting. Diabetes, 53, 2143–2152. [DOI] [PubMed] [Google Scholar]
  • 8.Barker N., van de Wetering M., and Clevers H. (2008) The intestinal stem cell. Genes Dev., 22, 1856–1864. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9.Fuchs E., and Horsley V. (2008) More than one way to skin. Genes Dev., 22, 976–985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10.Hopkins C., Li J., Rae F., and Little M.H. (2009) Stem cell options for kidney disease. J. Pathol., 217, 265–281. [DOI] [PubMed] [Google Scholar]
  • 11.Kajstura J., Urbanek K., Rota M., Bearzi C., Hosoda T., Bolli R., Anversa P., and Leri A. (2008) Cardiac stem cells and myocardial disease. J. Mol. Cell. Cardiol., 45, 505–513. [DOI] [PubMed] [Google Scholar]
  • 12.Zammit P.S. (2008) All muscle satellite cells are equal, but are some more equal than others? J. Cell Sci., 121, 2975–2982. [DOI] [PubMed] [Google Scholar]
  • 13.Ahmed S. (2009) The Culture of Neural Stem Cells. J. Cell. Biochem., 106, 1–6. [DOI] [PubMed] [Google Scholar]
  • 14.Nardi N.B., and Alfonso Z.Z. (1999) The hematopoietic stroma. Braz. J. Med. Biol. Res., 32, 601–609. [DOI] [PubMed] [Google Scholar]
  • 15.da Silva Meirelles L., and Nardi N.B. (2003) Murine marrow-derived mesenchymal stem cell: isolation, in vitro expansion, and characterization. Br. J. Haematol., 123, 702–711. [DOI] [PubMed] [Google Scholar]
  • 16.Friedenstein A.J., Chailakhjan R.K., and 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] [PubMed] [Google Scholar]
  • 17.da Silva Meirelles L., Caplan A.I., and Nardi N.B. (2008) In search of the in vivo identity of mesenchymal stem cells. Stem Cells, 26, 2287–2299. [DOI] [PubMed] [Google Scholar]
  • 18.Pittenger M.F., Mackay A.M., Beck S.C., Jaiswal R.K., Douglas R., Mosca J.D., Moorman M.A., Simonetti D.W., Craig S., and Marshak D.R. (1999) Multilineage potential of adult human mesenchymal stem cells. Science, 284, 143–147. [DOI] [PubMed] [Google Scholar]
  • 19.Dominici M., Le Blanc K., Mueller I., Slaper-Cortenbach I., Marini F., Krause D., Deans R., Keating A., Prockop D.J., and Horwitz R. (2006) Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy, 8, 315–317. [DOI] [PubMed] [Google Scholar]
  • 20.Horwitz E., Le Blanc M.K., Dominici M., Mueller I., Slaper-Cortenbach I., Marini F.C., Deans R.J., Krause D.S., and Keating A. (2005) Clarification of the nomenclature for MSC: The International Society for Cellular Therapy position statement. Cytotherapy, 7, 393–395. [DOI] [PubMed] [Google Scholar]
  • 21.Haniffa M.A., Collin M.P., Buckley C.D., and Dazzi F. (2009) Mesenchymal stem cells: the fibroblasts’ new clothes? Haematologica, 94, 258–63. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 22.da Silva Meirelles L., and Nardi N.B. (2009) Methodology, biology and clinical applications of mesenchymal stem cells. Front Biosci., 14, 4281–498. [DOI] [PubMed] [Google Scholar]
  • 23.Vrijsen K., Chamuleau S., Noort W., Doevendans P., and Sluijter J. (2009) Stem cell therapy for end-stage heart failure: indispensable role for the cell? Curr. Opin. Organ. Transplant., 14, 560–565. [DOI] [PubMed] [Google Scholar]
  • 24.Zhou Q., and Melton D.A. (2008) Extreme makeover: converting one cell into another. Cell Stem Cell, 3, 382–388. [DOI] [PubMed] [Google Scholar]
  • 25.Davani B., Ikonomou L., Raaka B.M., Geras-Raaka E., Morton R.A., Marcus-Samuels B., and Gershengorn M.C. (2007) Human islet-derived precursor cells are mesenchymal stromal cells that differentiate and mature to hormone-expressing cells in vivo. Stem Cells, 25, 3215–3222. [DOI] [PubMed] [Google Scholar]
  • 26.Karnieli O., Izhar-Prato Y., Bulvik S., and Efrat S. (2007) Generation of insulin-producing cells from human bone marrow mesenchymal stem cells by genetic manipulation. Stem Cells, 25, 2837–2844. [DOI] [PubMed] [Google Scholar]
  • 27.Barnabé G.F., Schwindt T.T., Calcagnotto M.R., Motta F.L., Martinez G. Jr., de Oliveira A.C., Keim L.M., D'Almeida V., Mendez-Otero R., and Mello L.E. (2009) Chemically-induced RAT mesenchymal stem cells adopt molecular properties of neuronal-like cells but do not have basic neuronal functional properties. PLoS ONE, 4, e5222. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 28.Nesselmann C., Ma N., Bieback K., Wagner W., Ho A., Konttinen Y.T., Zhang H., Hinescu M.E., and Steinhoff G. (2008) Mesenchymal stem cells and cardiac repair. J. Cell. Mol. Med., 12, 1795–1810. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 29.Schinkothe T., Bloch W., and Schmidt A. (2008) in vitro secreting profile of human mesenchymal stem cells. Stem Cells Dev., 17, 199–205. [DOI] [PubMed] [Google Scholar]
  • 30.Bernardo M.E., Zaffaroni N., Novara F., Cometa A.M., Avanzini M.A., Moretta A., Montagna D., Maccario R., Villa R., Daidone M.G., Zuffardi O., and Locatelli F. (2007) Human bone marrow derived mesenchymal stem cells do not undergo transformation after long-term in vitro culture and do not exhibit telomere maintenance mechanisms. Cancer Res., 67, 9142–9149. [DOI] [PubMed] [Google Scholar]
  • 31.Izadpanah R., Kaushal D., Kriedt C., Tsien F., Patel B., Dufour J., and Bunnell B.A. (2008) Long-term in vitro expansion alters the biology of adult mesenchymal stem cells. Cancer Res., 68, 4229–4238. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 32.Aguilar S., Nye E., Chan J., Loebinger M., Spencer-Dene B., Fisk N., Stamp G., Bonnet D., and Janes S.M. (2007) Murine but not human mesenchymal stem cells generate osteosarcoma-like lesions in the lung. Stem Cells, 25, 1586–1594. [DOI] [PubMed] [Google Scholar]
  • 33.Nasef A., Ashammakhi N., and Fouillard L. (2008) Immunomodulatory effect of mesenchymal stromal cells: possible mechanisms. Regen. Med., 3, 531–546. [DOI] [PubMed] [Google Scholar]
  • 34.Uccelli A., Moretta L., and Pistoia V. (2008) Mesenchymal stem cells in health and disease. Nat. Rev. Immunol., 8, 726–736. [DOI] [PubMed] [Google Scholar]
  • 35.Liotta F., Angeli R., Cosmi L., Fili L., Manuelli C., Fresali F., Mazzingui B., Maggi L., Pasini A., Lisi V., Santarlasci V., Consoloni L., Aangelotti M.L., Romagnani P., Parronchi P., Krampera M., Maggi E., Romagnani S., and Annunziato F. (2008) Toll-like receptors 3 and 4 are expressed by human bone marrow-derived mesenchymal stem cells and can inhibit their T-cell modulatory activity by impairing Notch signaling. Stem Cells, 26, 279–289. [DOI] [PubMed] [Google Scholar]
  • 36.Abdi R., Fiorina P., Adra C.N., Atkinson M., and Sayegh M.H. (2008) Immunomodulation by mesenchymal stem cells: a potential therapeutic strategy for type 1 diabetes. Diabetes, 57, 1759–1767. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 37.Giordano A., Galderisi U., and Marino I. R. (2007) From the laboratory bench to the patient's bedside: an update on clinical trials with mesenchymal stem cells. J. Cell Physiol., 211, 27–35. [DOI] [PubMed] [Google Scholar]
  • 38.Rosenzweig A. (2006) Cardiac cell therapy-mixed results from mixed cells. N. Engl. J. Med., 355, 1274–1277. [DOI] [PubMed] [Google Scholar]
  • 39.Kalil R.A., Ott D., Sant'Anna R., Dias E., Marques-Pereira J.P., Delgado-Cañedo A., Nardi N.B., Sant'Anna J.R., Prates P.R., and Nesralla I. (2008) Autologous transplantation of bone marrow mononuclear stem cells by minithoracotomy in dilated cardiomyopathy: technique and early results. Sao Paulo Med. J., 126, 75–81. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 40.Bernardo M.E., Locatelli F., and Fibbe W.E. (2009) Mesenchymal stromal cells. Ann. N.Y. Acad. Sci., 1176, 101–117. [DOI] [PubMed] [Google Scholar]
  • 41.Sudres M., Norol F., Trenado A., Grégoire S., Charlotte F., Levacher B., Lataillade J.J., Bourin P., Holy X., Vernant J.P., Klatzmann D., and Cohen J.L. (2006) Bone marrow mesenchymal stem cells suppress lymphocyte proliferation in vitro but fail to prevent graft-versus-host disease in mice. J. Immunol., 176, 7761–7767. [DOI] [PubMed] [Google Scholar]
  • 42.Tisato V., Naresh K., Girdlestone J., Navarrete C., and Dazzi F. (2007) Mesenchymal stem cells of cord blood origin are effective at preventing but not treating graft-versus-host disease. Leukemia, 21, 1992–1999. [DOI] [PubMed] [Google Scholar]
  • 43.Madec A.M., Mallone R., Afonso G., Abou Mrad E., Mesnier A., Eljaafari A., and Thivolet C. (2009) Mesenchymal stem cells protect NOD mice from diabetes by inducing regulatory T cells. Diabetologia, 52, 1391–1399. [DOI] [PubMed] [Google Scholar]
  • 44.Djouad F., Fritz V., Apparailly F., Louis-Plence P., Bony C., Sany J., Jorgensen C., and Noël D. (2005) Reversal of the immunosuppressive properties of mesenchymal stem cells by tumor necrosis factor alpha in collagen-induced arthritis. Arthritis Rheum., 52, 1595–1603. [DOI] [PubMed] [Google Scholar]
  • 45.Gonzalez M.A., Gonzalez-Rey E., Rico L., Buscher D., and Delgado M. (2009) Treatment of experimental arthritis by inducing immune tolerance with human adipose-derived mesenchymal stem cells. Arthritis Rheum., 60, 1006–1019. [DOI] [PubMed] [Google Scholar]
  • 46.Jones B.J., and McTaggarta S.J. (2008) Immunosuppression by mesenchymal stromal cells: From culture to clinic. Exp. Hematol., 36, 733–741. [DOI] [PubMed] [Google Scholar]
  • 47.Nakamizo A., Marini F., Amano T., Khan A., Studeny M., Gumin J., Chen J., Hentschel S., Vecil G., Dembinski J., Andreeff M., and Lang F.F. (2005) Human bone marrow-derived mesenchymal stem cells in the treatment of gliomas. Cancer Res., 65, 3307–3318. [DOI] [PubMed] [Google Scholar]
  • 48.Xu G., Jiang X.D., Xu Y., Zhang J., Huang F.H., Chen Z.Z., Zhou D.X., Shang J.H., Zou Y.X., Cai Y.Q., Kou S.B., Chen Y.Z., Xu R.X., and Zeng Y.J. (2009) Adenoviral-mediated interleukin-18 expression in mesenchymal stem cells effectively suppresses the growth of glioma in rats. Cell Biol. Int., 33, 466–474. [DOI] [PubMed] [Google Scholar]
  • 49.Djouad F., Plence P., Bony C., Tropel P., Apparailly F., Sany J., Noël D., and Jorgensen C. (2003) Immunosuppressive effect of mesenchymal stem cells favors tumor growth in allogeneic animals. Blood, 102, 3837–3844. [DOI] [PubMed] [Google Scholar]
  • 50.Mishra P.J., Mishra P.J., Glod J.W., and Banerjee D. (2009) Mesenchymal stem cells: flip side of the coin. Cancer Res., 69, 1255–1258. [DOI] [PubMed] [Google Scholar]

Articles from Science Progress are provided here courtesy of SAGE Publications

RESOURCES