Advertisement

MSCs: The Need to Rethink

Chapter
Part of the Stem Cell Biology and Regenerative Medicine book series (STEMCELL)

Abstract

It has long been known that within bone marrow, a non-hematopoietic stem cell, capable of reforming a complete skeletal segment exists. Originally termed a bone marrow stromal stem cell and later renamed a “mesenchymal” stem cell (“MSC”), this cell has the capability to form cartilage, bone, hematopoiesis-supportive stroma, and marrow adipocytes. Furthermore, this cell also organizes marrow vasculature and is a component of the HSC niche, properties that make this cell inherently unique. Based on its cell surface properties (that solely represent connective tissue cells) and the use of less than stringent in vitro differentiation assays, “MSCs” have been reported to be found in virtually any connective tissue, with extensive differentiation capacities. Yet by rigorous criteria, MSCs from different tissues are not the same, are not ubiquitous, and they are not pluripotent. Considering the current interest in the use of MSCs from all types of tissues for not only tissue engineering but also in regenerative medicine (using the cells as a drug), there is an urgent need to get specific about the biology of MSCs from different tissues: what they are, where they came from, and what they can really do.

Keywords

Stem Cell Epidermolysis Bullosa Skeletal Tissue Connective Tissue Cell Mural Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

This work was funded by MIUR, Fondations Roxa Fondations Cevei Bowauetti and Telethon-Grant GGP09227 (PB) and by the DIR, NIDCR of the IRP, NIH, DHHS (PGR).

References

  1. 1.
    Tavassoli M, Crosby WH (1968) Transplantation of marrow to extramedullary sites. Science 161(836):54–56PubMedCrossRefGoogle Scholar
  2. 2.
    Friedenstein AJ, Petrakova KV, Kurolesova AI, Frolova GP (1968) Heterotopic transplants of bone marrow.Analysis of precursor cells for osteogenic and hematopoietic tissues. Transplantation 6(2):230–247PubMedCrossRefGoogle Scholar
  3. 3.
    Friedenstein AJ, Chailakhjan RK, Lalykina KS (1970) The development of fibroblast colonies in monolayer cultures of guinea - pig bone marrow and spleen cells. Cell Tissue Kinet 3(4):393–403PubMedGoogle Scholar
  4. 4.
    Friedenstein AJ, Chailakhyan RK, Latsinik NV, Panasyuk AF, Keiliss-Borok IV (1974) Stromal cells responsible for transferring the microenvironment of the hemopoietic tissues cloning in vitro and retransplantation in vivo. Transplantation 17(4):331–340PubMedCrossRefGoogle Scholar
  5. 5.
    Owen M, Friedenstein AJ (1988) Stromal stem cells: marrow-derived osteogenic precursors. Ciba Found Symp 136:42–60PubMedGoogle Scholar
  6. 6.
    Sacchetti B, Funari A, Michienzi S, Di Cesare S, Piersanti S, Saggio I et al (2007) Self-renewing osteoprogenitors in bone marrow sinusoids can organize a hematopoietic microenvironment. Cell 131:324–336PubMedCrossRefGoogle Scholar
  7. 7.
    Mendez-Ferrer S, Michurina TV, Ferraro F, Mazloom AR, Macarthur BD, Lira SA et al (2010) Mesenchymal and haematopoietic stem cells form a unique bone marrow niche. Nature 466(7308):829–834PubMedCrossRefGoogle Scholar
  8. 8.
    Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D et al (2006) Minimal criteria for defining multipotent mesenchymal stromal cells.The International Society for Cellular Therapy position statement. Cytotherapy 8(4):315–317PubMedCrossRefGoogle Scholar
  9. 9.
    Crisan M, Yap S, Casteilla L, Chen CW, Corselli M, Park TS et al (2008) A perivascular origin for mesenchymal stem cells in multiple human organs. Cell Stem Cell 3(3):301–313PubMedCrossRefGoogle Scholar
  10. 10.
    Bianco P, Robey PG, Simmons PJ (2008) Mesenchymal stem cells: revisiting history, concepts, and assays. Cell Stem Cell 2(4):313–319PubMedCrossRefGoogle Scholar
  11. 11.
    Zimmermann S, Voss M, Kaiser S, Kapp U, Waller CF, Martens UM (2003) Lack of telomerase activity in human mesenchymal stem cells. Leukemia 17(6):1146–1149PubMedCrossRefGoogle Scholar
  12. 12.
    Bianco P, Riminucci M, Kuznetsov S, Robey PG (1999) Multipotential cells in the bone marrow stroma: regulation in the context of organ physiology. Crit Rev Eukaryot Gene Expr 9(2):159–173PubMedCrossRefGoogle Scholar
  13. 13.
    Weiss L (1976) The hematopoietic microenvironment of the bone marrow: an ultrastructural study of the stroma in rats. Anat Rec 186(2):161–184PubMedCrossRefGoogle Scholar
  14. 14.
    Westen H, Bainton DF (1979) Association of alkaline-phosphatase-positive reticulum cells in bone marrow with granulocytic precursors. J Exp Med 150(4):919–937PubMedCrossRefGoogle Scholar
  15. 15.
    Bianco P, Boyde A (1993) Confocal images of marrow stromal (Westen-Bainton) cells. Histochemistry 100(2):93–99PubMedCrossRefGoogle Scholar
  16. 16.
    Bianco P, Bradbeer JN, Riminucci M, Boyde A (1993) Marrow stromal (Western-Bainton) cells: identification, morphometry, confocal imaging and changes in disease. Bone 14(3):315–320PubMedCrossRefGoogle Scholar
  17. 17.
    Bianco P, Riminucci M (1998) The bone marrow stroma in vivo: ontogeny, sturcutre, cellular composition and changes in disease. In: Beresford JN, Owen M (eds) Marrow stromal cell culture. Cambridge University Press, Cambridge, U.KGoogle Scholar
  18. 18.
    Bianco P, Gehron Robey P (2000) Marrow stromal stem cells. J Clin Invest 105(12):1663–1668PubMedCrossRefGoogle Scholar
  19. 19.
    Bianco P, Riminucci M, Gronthos S, Robey PG (2001) Bone marrow stromal stem cells: nature, biology, and potential applications. Stem Cells 19(3):180–192PubMedCrossRefGoogle Scholar
  20. 20.
    Suri C, Jones PF, Patan S, Bartunkova S, Maisonpierre PC, Davis S et al (1996) Requisite role of angiopoietin-1, a ligand for the TIE2 receptor, during embryonic angiogenesis. Cell 87(7):1171–1180PubMedCrossRefGoogle Scholar
  21. 21.
    Arai F, Ohneda O, Miyamoto T, Zhang XQ, Suda T (2002) Mesenchymal stem cells in perichondrium express activated leukocyte cell adhesion molecule and participate in bone marrow formation. J Exp Med 195(12):1549–1563PubMedCrossRefGoogle Scholar
  22. 22.
    Doherty MJ, Ashton BA, Walsh S, Beresford JN, Grant ME, Canfield AE (1998) Vascular pericytes express osteogenic potential in vitro and in vivo. J Bone Miner Res 13(5):828–838PubMedCrossRefGoogle Scholar
  23. 23.
    Diaz-Flores L, Gutierrez R, Madrid JF, Varela H, Valladares F, Acosta E et al (2009) Pericytes. Morphofunction, interactions and pathology in a quiescent and activated mesenchymal cell niche. Histol Histopathol 24(7):909–969PubMedGoogle Scholar
  24. 24.
    Streeter GL (1949) Developmental horizons in human embryos: review of the histogenesis of cartilage and bone. Contrib Embryol Carneg Inst 33(4):149–169Google Scholar
  25. 25.
    Bianco P, Riminucci M, Bonucci E, Termine JD, Robey PG (1993) Bone sialoprotein (BSP) secretion and osteoblast differentiation: relationship to bromodeoxyuridine incorporation, alkaline phosphatase, and matrix deposition. J Histochem Cytochem 41(2):183–191PubMedCrossRefGoogle Scholar
  26. 26.
    Maes C, Kobayashi T, Selig MK, Torrekens S, Roth SI, Mackem S et al (2010) Osteoblast precursors, but not mature osteoblasts, move into developing and fractured bones along with invading blood vessels. Dev Cell 19(2):329–344PubMedCrossRefGoogle Scholar
  27. 27.
    Dellavalle A, Sampaolesi M, Tonlorenzi R, Tagliafico E, Sacchetti B, Perani L et al (2007) Pericytes of human skeletal muscle are myogenic precursors distinct from satellite cells. Nat Cell Biol 9(3):255–267PubMedCrossRefGoogle Scholar
  28. 28.
    Caplan AI (2008) All MSCs are pericytes? Cell Stem Cell 3(3):229–230PubMedCrossRefGoogle Scholar
  29. 29.
    da Silva Meirelles L, Chagastelles PC, Nardi NB (2006) Mesenchymal stem cells reside in virtually all post-natal organs and tissues. J Cell Sci 119(Pt 11):2204–2213PubMedCrossRefGoogle Scholar
  30. 30.
    Sims DE (2000) Diversity within pericytes. Clin Exp Pharmacol Physiol 27(10):842–846PubMedCrossRefGoogle Scholar
  31. 31.
    Simmons PJ, Torok-Storb B (1991) Identification of stromal cell precursors in human bone marrow by a novel monoclonal antibody, STRO-1. Blood 78(1):55–62PubMedGoogle Scholar
  32. 32.
    Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS et al (1998) Embryonic stem cell lines derived from human blastocysts. Science 282(5391):1145–1147PubMedCrossRefGoogle Scholar
  33. 33.
    Jiang Y, Jahagirdar BN, Reinhardt RL, Schwartz RE, Keene CD, Ortiz-Gonzalez XR et al (2002) Pluripotency of mesenchymal stem cells derived from adult marrow. Nature 418(6893):41–49PubMedCrossRefGoogle Scholar
  34. 34.
    Yoon J, Shim WJ, Ro YM, Lim DS (2005) Transdifferentiation of mesenchymal stem cells into cardiomyocytes by direct cell-to-cell contact with neonatal cardiomyocyte but not adult cardiomyocytes. Ann Hematol 84(11):715–721PubMedCrossRefGoogle Scholar
  35. 35.
    Kopen GC, Prockop DJ, Phinney DG (1999) Marrow stromal cells migrate throughout forebrain and cerebellum, and they differentiate into astrocytes after injection into neonatal mouse brains. Proc Natl Acad Sci USA 96(19):10711–10716PubMedCrossRefGoogle Scholar
  36. 36.
    Zipori D (2004) Mesenchymal stem cells: harnessing cell plasticity to tissue and organ repair. Blood Cells Mol Dis 33(3):211–215PubMedCrossRefGoogle Scholar
  37. 37.
    Calvi LM, Adams GB, Weibrecht KW, Weber JM, Olson DP, Knight MC et al (2003) Osteoblastic cells regulate the haematopoietic stem cell niche. Nature 425(6960):841–846PubMedCrossRefGoogle Scholar
  38. 38.
    Zhang J, Niu C, Ye L, Huang H, He X, Tong WG et al (2003) Identification of the haematopoietic stem cell niche and control of the niche size. Nature 425(6960):836–841PubMedCrossRefGoogle Scholar
  39. 39.
    Kiel MJ, Yilmaz OH, Iwashita T, Terhorst C, Morrison SJ (2005) SLAM family receptors distinguish hematopoietic stem and progenitor cells and reveal endothelial niches for stem cells. Cell 121(7):1109–1121PubMedCrossRefGoogle Scholar
  40. 40.
    Bianco P (2011) Bone and the hematopoietic niche: a tale of two stem cells. Blood 117(20):5281–5288PubMedCrossRefGoogle Scholar
  41. 41.
    Chan CK, Chen CC, Luppen CA, Kim JB, DeBoer AT, Wei K et al (2009) Endochondral ossification is required for haematopoietic stem-cell niche formation. Nature 457(7228):490–494PubMedCrossRefGoogle Scholar
  42. 42.
    Omatsu Y, Sugiyama T, Kohara H, Kondoh G, Fujii N, Kohno K et al (2010) The essential functions of adipo-osteogenic progenitors as the hematopoietic stem and progenitor cell niche. Immunity 33(3):387–399PubMedCrossRefGoogle Scholar
  43. 43.
    Ding L, Saunders TL, Enikolopov G, Morrison SJ (2012) Endothelial and perivascular cells maintain haematopoietic stem cells. Nature 481(7382):457–462PubMedCrossRefGoogle Scholar
  44. 44.
    Park D, Sykes DB, Scadden DT (2012) The hematopoietic stem cell niche. Front Biosci 17:30–39PubMedCrossRefGoogle Scholar
  45. 45.
    Au P, Tam J, Fukumura D, Jain RK (2008) Bone marrow-derived mesenchymal stem cells facilitate engineering of long-lasting functional vasculature. Blood 111(9):4551–4558PubMedCrossRefGoogle Scholar
  46. 46.
    Moioli EK, Clark PA, Chen M, Dennis JE, Erickson HP, Gerson SL et al (2008) Synergistic actions of hematopoietic and mesenchymal stem/progenitor cells in vascularizing bioengineered tissues. PLoS One 3(12):e3922PubMedCrossRefGoogle Scholar
  47. 47.
    Melero-Martin JM, De Obaldia ME, Kang SY, Khan ZA, Yuan L, Oettgen P et al (2008) Engineering robust and functional vascular networks in vivo with human adult and cord blood-derived progenitor cells. Circ Res 103(2):194–202PubMedCrossRefGoogle Scholar
  48. 48.
    Caplan AI, Correa D (2011) The MSC: an injury drugstore. Cell Stem Cell 9(1):11–15PubMedCrossRefGoogle Scholar
  49. 49.
    Lee RH, Pulin AA, Seo MJ, Kota DJ, Ylostalo J, Larson BL et al (2009) Intravenous hMSCs improve myocardial infarction in mice because cells embolized in lung are activated to secrete the anti-inflammatory protein TSG-6. Cell Stem Cell 5(1):54–63PubMedCrossRefGoogle Scholar
  50. 50.
    Thomas ED, Lochte HL Jr, Lu WC, Ferrebee JW (1957) Intravenous infusion of bone marrow in patients receiving radiation and chemotherapy. N Engl J Med 257(11):491–496PubMedCrossRefGoogle Scholar
  51. 51.
    Till JE, McCulloch EA (1961) A direct measurement of the radiation sensitivity of normal mouse bone marrow cells. Radiat Res 14:213–222PubMedCrossRefGoogle Scholar
  52. 52.
    Notta F, Doulatov S, Laurenti E, Poeppl A, Jurisica I, Dick JE (2011) Isolation of single human hematopoietic stem cells capable of long-term multilineage engraftment. Science 333(6039):218–221PubMedCrossRefGoogle Scholar
  53. 53.
    Blanpain C, Horsley V, Fuchs E (2007) Epithelial stem cells: turning over new leaves. Cell 128(3):445–458PubMedCrossRefGoogle Scholar
  54. 54.
    Beck B, Blanpain C (2012) Mechanisms regulating epidermal stem cells. EMBO J 31(9):2067–2075PubMedCrossRefGoogle Scholar
  55. 55.
    Congdon CC, Uphoff D, Lorenz E (1952) Modification of acute irradiation injury in mice and guinea pigs by injection of bone marrow; a histopathologic study. J Natl Cancer Inst 13(1):73–107PubMedGoogle Scholar
  56. 56.
    Aiuti A, Slavin S, Aker M, Ficara F, Deola S, Mortellaro A et al (2002) Correction of ADA-SCID by stem cell gene therapy combined with nonmyeloablative conditioning. Science 296(5577):2410–2413PubMedCrossRefGoogle Scholar
  57. 57.
    Mavilio F, Pellegrini G, Ferrari S, Di Nunzio F, Di Iorio E, Recchia A et al (2006) Correction of junctional epidermolysis bullosa by transplantation of genetically modified epidermal stem cells. Nat Med 12(12):1397–1402PubMedCrossRefGoogle Scholar
  58. 58.
    Piersanti S, Remoli C, Saggio I, Funari A, Michienzi S, Sacchetti B et al (2010) Transfer, analysis, and reversion of the fibrous dysplasia cellular phenotype in human skeletal progenitors. J Bone Miner Res 25(5):1103–1116PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Department of Molecular MedicineSapienza University of RomeRomeItaly
  2. 2.Department of Health and Human ServicesCraniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institutes of HealthBethesdaUSA

Personalised recommendations