Skip to main content
SpringerLink
Log in

Mesenchymal stem cells

Lineage, plasticity, and skeletal therapeutic potential

  • Original Article
  • Published:
Stem Cell Reviews Aims and scope Submit manuscript

Abstract

The tremendous capacity of bone to regenerate is indicative of the presence of stem cells with the capability, by definition, to self-renew as well as to give rise to daughter cells. These primitive progenitors, termed mesenchymal stem cells or bone marrow stromal stem cells, exist postnatally, and are multipotent with the ability to generate cartilage, bone, muscle, tendon, ligament, and fat. Given the demographic challenge of an ageing population, the development of strategies to exploit the potential of stem cells to augment bone formation to replace or restore the function of traumatized, diseased, or degenerated bone is a major clinical and socioeconomic need. Owing to the developmental plasticity of mesenchymal stem cells, there is great interest in their application to replace damaged tissues. Combined with modern advances in gene therapy and tissue engineering, they have the potential to improve the quality of life for many. Critical in the development of this field will be an understanding of the phenotype, plasticity, and potentiality of these cells and the tempering of patients’ expectations driven by commercial and media hype to match current laboratory and clinical observations.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Ding S, Wu TY, Brinker A, et al. Proc Natl Acad Sci USA 2003;100:7632–7637.

    Article  PubMed  CAS  Google Scholar 

  2. Wu X, Ding S, Ding Q, Gray NS, Schultz PG. J Am Chem Soc 2004;126:1590–1591.

    Article  PubMed  CAS  Google Scholar 

  3. Gaspar HB, Howe S, Thrasher AJ. Gene Ther 2003;10:1999–2004.

    Article  PubMed  CAS  Google Scholar 

  4. Hubel K, Engert A. Ann Hematol 2003;82:207–213.

    PubMed  CAS  Google Scholar 

  5. Perin EC, Dohmann HF, Borojevic R, et al. Circulation 2003;107:2294–2302.

    Article  PubMed  Google Scholar 

  6. Menasche P. Surg Clin North Am 2004;84:125–139.

    Article  PubMed  Google Scholar 

  7. Friedenstein AJ, Petrakova KV, Kurolesova AI, Frolova GP. Transplantation 1968;6:230–247.

    Article  PubMed  CAS  Google Scholar 

  8. Friedenstein AJ. Int Rev Cytol 1976;47:327–359.

    Article  PubMed  CAS  Google Scholar 

  9. Friedenstein AJ, Ivanov-Smolenski AA, Chajlakjan RK, et al. Exp Hematol 1978;6:440–444.

    PubMed  CAS  Google Scholar 

  10. Triffitt JT. J Cell Biochem Suppl 2002;38:13–19.

    Article  PubMed  CAS  Google Scholar 

  11. Owen M, Friedenstein AJ. Ciba Found Symp 1988;136:42–60.

    PubMed  CAS  Google Scholar 

  12. Goshima J, Goldberg VM, Caplan AI. Clin Orthop 1991;262:298–311.

    PubMed  Google Scholar 

  13. Bianco P, Robey PG. Nature 2001;414:118–121.

    Article  PubMed  CAS  Google Scholar 

  14. Lajtha LG. Differentiation 1979;14:23–34.

    Article  PubMed  CAS  Google Scholar 

  15. Lovell-Badge R. Nature 2001;414:88–91.

    Article  PubMed  CAS  Google Scholar 

  16. Bianco P, Riminucci M, Gronthos S, Robey PG. Stem Cells 2001;19:180–192.

    Article  PubMed  CAS  Google Scholar 

  17. Jiang Y, Jahagirdar BN, Reinhardt RL, et al. Nature 2002;418:41–49.

    Article  PubMed  CAS  Google Scholar 

  18. Verfaillie CM. Trends Cell Biol 2002;12:502–508.

    Article  PubMed  CAS  Google Scholar 

  19. Pittenger MF, Mackay AM, Beck SC, et al. Science 1999;284:143–147.

    Article  PubMed  CAS  Google Scholar 

  20. Aubin JE, Triffitt JT. In: Principles of Bone Biology, 2nd Edition (Bilezkikian JP, Raisz LG, and Rodan GA, eds). Academic, NY: 2002;59–81.

    Google Scholar 

  21. Bruder SP, Horowitz MC, Mosca JD, Haynesworth SE. Bone 1997;21:225–235.

    Article  PubMed  CAS  Google Scholar 

  22. Simmons PJ, Torok-Storb B. Blood 1991;78:2848–2853.

    PubMed  CAS  Google Scholar 

  23. Gronthos S, Simmons PJ. Blood 1995;85:929–940.

    PubMed  CAS  Google Scholar 

  24. Gronthos S, Zannettino AC, Graves SE, Ohta S, Hay SJ, Simmons PJ. J Bone Miner Res 1999;14:47–56.

    Article  PubMed  CAS  Google Scholar 

  25. Haynesworth SE, Baber MA, Caplan AI. Bone 1992;13:69–80.

    Article  PubMed  CAS  Google Scholar 

  26. Joyner CJ, Bennett A, Triffitt JT. Bone 1997;21:1–6.

    Article  PubMed  CAS  Google Scholar 

  27. Gronthos S, Graves SE, Ohta S, Simmons PJ. Blood 1994;84:4164–4173.

    PubMed  CAS  Google Scholar 

  28. Stewart K, Walsh S, Screen J, et al. J Bone Miner Res 1999;14:1345–1356.

    Article  PubMed  CAS  Google Scholar 

  29. Howard D, Partridge K, Yang X, et al. Biochem Biophys Res Commun 2002;299:208–215.

    Article  PubMed  CAS  Google Scholar 

  30. Bruder SP, Ricalton NS, Boynton RE, et al. J Bone Miner Res 1998;13:655–663.

    Article  PubMed  CAS  Google Scholar 

  31. Barry FP, Boynton RE, Haynesworth S, Murphy JM, Zaia J. Biochem Biophys Res Commun 1999;265:134–139.

    Article  PubMed  CAS  Google Scholar 

  32. Triffitt JT, Oreffo RO, Virdi AS, Xia Z. Cytotherapy 2001;3:413–416.

    Article  PubMed  CAS  Google Scholar 

  33. Gronthos S, Zannettino AC, Hay SJ, et al. J Cell Sci 2003;116:1827–1835.

    Article  PubMed  CAS  Google Scholar 

  34. Waller EK, Olweus J, Lund-Johansen F, et al. Blood 1995;85:2422–2435.

    PubMed  CAS  Google Scholar 

  35. Jones EA, Kinsey SE, English A, et al. Arthritis Rheum 2002;46:3349–3360.

    Article  PubMed  Google Scholar 

  36. Park SR, Oreffo RO, Triffitt JT. Bone 1999;24:549–554.

    Article  PubMed  CAS  Google Scholar 

  37. Kuznetsov SA, Mankani MH, Gronthos S, Satomura K, Bianco P, Robey PG. J Cell Biol 2001;153:1133–1140.

    Article  PubMed  CAS  Google Scholar 

  38. Friedenstein AJ, Deriglasova UF, Kulagina NN, et al. Exp Hematol 1974;2:83–92.

    PubMed  CAS  Google Scholar 

  39. Triffitt JT, Oreffo ROC. In: Molecular and Cellular Biology of Bone (Zaidi M, ed.). JAI, CT: 1998;429–451.

    Google Scholar 

  40. Nuttall ME, Gimble JM. Bone 2000;27:177–184.

    Article  PubMed  CAS  Google Scholar 

  41. Nuttall ME, Patton AJ, Olivera DL, Nadeau DP, Gowen M. J Bone Miner Res 1998;13:371–382.

    Article  PubMed  CAS  Google Scholar 

  42. Krause DS. Gene Ther 2002;9:754–758.

    Article  PubMed  CAS  Google Scholar 

  43. Ferrari G, Cusella-De Angelis G, Coletta M, et al. Science 1998;279:1528–1530.

    Article  PubMed  CAS  Google Scholar 

  44. Sanchez-Ramos J, Song S, Cardozo-Pelaez F, et al. Exp Neurol 2000;164:247–256.

    Article  PubMed  CAS  Google Scholar 

  45. Reyes M, Lund T, Lenvik T, Aguiar D, Koodie L, Verfaillie CM. Blood 2001;98:2615–2625.

    Article  PubMed  CAS  Google Scholar 

  46. Reyes M, Dudek A, Jahagirdar B, Koodie L, Marker PH, Verfaillie CM. J Clin Invest 2002;109:337–346.

    Article  PubMed  CAS  Google Scholar 

  47. Schwartz RE, Reyes M, Koodie L, et al. J Clin Invest 2002;109:1291–1302.

    Article  PubMed  CAS  Google Scholar 

  48. Vassilopoulos G, Wang PR, Russell DW. Nature 2003;422:901–904.

    Article  PubMed  CAS  Google Scholar 

  49. Wang X, Willenbring H, Akkari Y, et al. Nature 2003;422:897–901.

    Article  PubMed  CAS  Google Scholar 

  50. Kuznetsov SA, Friedenstein AJ, Robey PG. Br J Haematol 1997;97:561–570.

    Article  PubMed  CAS  Google Scholar 

  51. Oreffo RO, Romberg S, Virdi AS, Joyner CJ, Berven S, Triffitt JT. J Cell Biochem 1999;74:372–385.

    Article  PubMed  CAS  Google Scholar 

  52. Walsh S, Jefferiss C, Stewart K, Jordan GR, Screen J, Beresford JN. Bone 2000;27:185–195.

    Article  PubMed  CAS  Google Scholar 

  53. Tsutsumi S, Shimazu A, Miyazaki K, et al. Biochem Biophys Res Commun 2001;288:413–419.

    Article  PubMed  CAS  Google Scholar 

  54. Martin I, Muraglia A, Campanile G, Cancedda R, Quarto R. Endocrinology 1997;138:4456–4462.

    Article  PubMed  CAS  Google Scholar 

  55. Wozney JM, Rosen V. Clin Orthop 1998;346:26–37.

    PubMed  Google Scholar 

  56. Chen D, Ji X, Harris MA, et al. J Cell Biol 1998;142:295–305.

    Article  PubMed  CAS  Google Scholar 

  57. Pfeilschifter J, Wolf O, Naumann A, Minne HW, Mundy GR, Ziegler R. J Bone Miner Res 1990;5:825–830.

    PubMed  CAS  Google Scholar 

  58. Locklin RM, Oreffo RO, Triffitt JT. Cell Biol Int 1999;23:185–194.

    Article  PubMed  CAS  Google Scholar 

  59. Walsh S, Jefferiss C, Stewart K, Beresford JN. Cell Tissue Res 2003;311:187–198.

    PubMed  CAS  Google Scholar 

  60. Wang EA, Israel DI, Kelly S, Luxenberg DP. Growth Factors 1993;9:57–71.

    PubMed  CAS  Google Scholar 

  61. Rickard DJ, Sullivan TA, Shenker BJ, Leboy PS, Kazhdan I. Dev Biol 1994;161:218–228.

    Article  PubMed  Google Scholar 

  62. Locklin RM, Williamson MC, Beresford JN, Triffitt JT, Owen ME. Clin Orthop 1995;313:27–35.

    PubMed  Google Scholar 

  63. Oreffo RO, Virdi AS, Triffitt JT. Eur J Cell Biol 1997;74:251–261.

    PubMed  CAS  Google Scholar 

  64. Cheng SL, Yang JW, Rifas L, Zhang SF, Avioli LV. Endocrinology 1994;134:277–286.

    Article  PubMed  CAS  Google Scholar 

  65. Kimoto S, Cheng SL, Zhang SF, Avioli LV. Endocrinology 1994;135:2423–2431.

    Article  PubMed  CAS  Google Scholar 

  66. Walsh S, Jordan GR, Jefferiss C, Stewart K, Beresford JN. Rheumatology (Oxford) 2001;40:74–83.

    Article  CAS  Google Scholar 

  67. Beresford JN, Joyner CJ, Devlin C, Triffitt JT. Arch Oral Biol 1994;39:941–947.

    Article  PubMed  CAS  Google Scholar 

  68. Scutt A, Bertram P. J Bone Miner Res 1995;10:474–487.

    PubMed  CAS  Google Scholar 

  69. Still K, Scutt A. Prostaglandins Other Lipid Mediat 2001;65:21–31.

    Article  PubMed  CAS  Google Scholar 

  70. Kasugai S, Oida S, Iimura T, et al. Bone 1995;17:1–4.

    Article  PubMed  CAS  Google Scholar 

  71. Oreffo ROC, Wells N, Johnstone D. J Bone Miner Res 1991;6:S208.

    Google Scholar 

  72. Yang X, Tare RS, Partridge KA, et al. J Bone Miner Res 2003;18:47–57.

    Article  PubMed  CAS  Google Scholar 

  73. Tare RS, Oreffo RO, Clarke NM, Roach HI. J Bone Miner Res 2002;17:2009–2020.

    Article  PubMed  CAS  Google Scholar 

  74. Jilka RL. Bone 1998;23:75–81.

    Article  PubMed  CAS  Google Scholar 

  75. Manolagas SC, Jilka RL. N Engl J Med 1995;332:305–311.

    Article  PubMed  CAS  Google Scholar 

  76. Boyce BF, Aufdemorte TB, Garrett IR, Yates AJ, Mundy GR. Endocrinology 1989;125:1142–1150.

    Article  PubMed  CAS  Google Scholar 

  77. Nishida S, Endo N, Yamagiwa H, Tanizawa T, Takahashi HE. J Bone Miner Metab 1999;17:171–177.

    Article  PubMed  CAS  Google Scholar 

  78. D’Ippolito G, Schiller PC, Ricordi C, Roos BA, Howard GA. J Bone Miner Res 1999;14:1115–1122.

    Article  PubMed  CAS  Google Scholar 

  79. Majors AK, Boehm CA, Nitto H, Midura RJ, Muschler GF. J Orthop Res 1997;15:546–557.

    Article  PubMed  CAS  Google Scholar 

  80. Egrise D, Martin D, Vienne A, Neve P, Schoutens A. Bone 1992;13:355–361.

    Article  PubMed  CAS  Google Scholar 

  81. Bergman RJ, Gazit D, Kahn AJ, Gruber H, McDougall S, Hahn TJ. J Bone Miner Res 1996;11:568–577.

    PubMed  CAS  Google Scholar 

  82. Oreffo RO, Bennett A, Carr AJ, Triffitt JT. Scand J Rheumatol 1998;27:415–424.

    Article  PubMed  CAS  Google Scholar 

  83. Oreffo RO, Bord S, Triffitt JT. Clin Sci (Colch) 1998;94:549–555.

    CAS  Google Scholar 

  84. Marcotte R, Wang E. J Gerontol A Biol Sci Med Sci 2002;57:B257-B269.

    PubMed  Google Scholar 

  85. Pedro De MJ. Exp Cell Res 2004;300:1–10.

    Article  CAS  Google Scholar 

  86. Zimmermann S, Voss M, Kaiser S, Kapp U, Waller CF, Martens UM. Leukemia 2003;17:1146–1149.

    Article  PubMed  CAS  Google Scholar 

  87. Okamoto T, Aoyama T, Nakayama T, et al. Biochem Biophys Res Commun 2002;295:354–361.

    Article  PubMed  CAS  Google Scholar 

  88. Shi S, Gronthos S, Chen S, et al. Nat Biotechnol 2002;20:587–591.

    Article  PubMed  CAS  Google Scholar 

  89. Simonsen JL, Rosada C, Serakinci N, et al. Nat Biotechnol 2002;20:592–596.

    Article  PubMed  CAS  Google Scholar 

  90. Serakinci N, Guldberg P, Burns JS, et al. Oncogene 2004;23:5095–5098.

    Article  PubMed  CAS  Google Scholar 

  91. Stenderup K, Justesen J, Eriksen EF, Rattan SI, Kassem M. J Bone Miner Res 2001;16:1120–1129.

    Article  PubMed  CAS  Google Scholar 

  92. Pfeilschifter J, Diel I, Pilz U, Brunotte K, Naumann A, Ziegler R. J Bone Miner Res 1993;8:707–717.

    PubMed  CAS  Google Scholar 

  93. Erdmann J, Kogler C, Diel I, Ziegler R, Pfeilschifter J. Mech Ageing Dev 1999;110:73–85.

    Article  PubMed  CAS  Google Scholar 

  94. [No authors listed]. Am J Med 1993;94:646–650.

  95. Melton LJ, III, Chrischilles EA, Cooper C, Lane AW, Riggs BL. J Bone Miner Res 1992;7:1005–1010.

    Article  PubMed  Google Scholar 

  96. Cooper C. Am J Med 1997;103:12S-17S.

    Article  PubMed  CAS  Google Scholar 

  97. Christodoulou C, Cooper C. Postgrad Med J 2003;79:133–138.

    Article  PubMed  CAS  Google Scholar 

  98. Spector M. Orthop Clin North Am 1992;23:211–217.

    PubMed  CAS  Google Scholar 

  99. Rose FR, Oreffo RO. Biochem Biophys Res Commun 2002;292:1–7.

    Article  PubMed  CAS  Google Scholar 

  100. Langer R, Vacanti JP. Science 1993;260:920–926.

    Article  PubMed  CAS  Google Scholar 

  101. Kadiyala S, Young RG, Thiede MA, Bruder SP. Cell Transplant 1997;6:125–134.

    Article  PubMed  CAS  Google Scholar 

  102. Gundle R, Joyner CJ, Triffitt JT. Bone 1995;16:597–601.

    Article  PubMed  CAS  Google Scholar 

  103. Nakahara H, Bruder SP, Haynesworth SE, et al. Bone 1990;11:181–188.

    Article  PubMed  CAS  Google Scholar 

  104. Ohgushi H, Goldberg VM, Caplan AI. J Orthop Res 1989;7:568–578.

    Article  PubMed  CAS  Google Scholar 

  105. Simmons PJ, Torok-Storb B. Blood 1991;78:55–62.

    PubMed  CAS  Google Scholar 

  106. Stewart K, Walsh S, Screen J, et al. J Bone Miner Res 1999;14:1345–1356.

    Article  PubMed  CAS  Google Scholar 

  107. Bruder SP, Jaiswal N, Haynesworth SE. J Cell Biochem 1997;64:278–294.

    Article  PubMed  CAS  Google Scholar 

  108. Jaiswal N, Haynesworth SE, Caplan AI, Bruder SP. J Cell Biochem 1997;64:295–312.

    Article  PubMed  CAS  Google Scholar 

  109. Bartholomew A, Sturgeon C, Siatskas M, et al. Exp Hematol 2002;30:42–48.

    Article  PubMed  Google Scholar 

  110. Di Nicola M, Carlo-Stella C, Magni M, et al. Blood 2002;99:3838–3843.

    Article  PubMed  Google Scholar 

  111. Arinzeh TL, Peter SJ, Archambault MP, et al. J Bone Joint Surg Am 2003;85A:1927–1935.

    Google Scholar 

  112. Horwitz EM, Prockop DJ, Fitzpatrick LA, et al. Nat Med 1999;5:309–313.

    Article  PubMed  CAS  Google Scholar 

  113. Horwitz EM, Prockop DJ, Gordon PL, et al. Blood 2001;97:1227–1231.

    Article  PubMed  CAS  Google Scholar 

  114. Dominici M, Hofmann TJ, Horwitz EM. J Biol Regul Homeost Agents 2001;15:28–37.

    PubMed  CAS  Google Scholar 

  115. Connolly JF. Clin Orthop 1995;313:8–18.

    PubMed  Google Scholar 

  116. Quarto R, Mastrogiacomo M, Cancedda R, et al. N Engl J Med 2001;344:385–386.

    Article  PubMed  CAS  Google Scholar 

  117. Perry CR. Clin Orthop 1999;360:71–86.

    Article  PubMed  Google Scholar 

  118. Boden SD. Clin Orthop 1999;367:S84-S94.

    Article  PubMed  Google Scholar 

  119. Oreffo RO, Triffitt JT. Bone 1999;25:5S-9S.

    Article  PubMed  CAS  Google Scholar 

  120. Lieberman JR, Daluiski A, Stevenson S, et al. J Bone Joint Surg Am 1999;81:905–917.

    PubMed  CAS  Google Scholar 

  121. Breitbart AS, Grande DA, Mason JM, Barcia M, James T, Grant RT. Ann Plast Surg 1999;42:488–495.

    Article  PubMed  CAS  Google Scholar 

  122. Olmsted EA, Blum JS, Rill D, et al. J Cell Biochem 2001;82:11–21.

    Article  PubMed  CAS  Google Scholar 

  123. Turgeman G, Pittman DD, Muller R, et al. J Gene Med 2001;3:240–251.

    Article  PubMed  CAS  Google Scholar 

  124. Partridge K, Yang X, Clarke NM, et al. Biochem Biophys Res Commun 2002;292:144–152.

    Article  PubMed  CAS  Google Scholar 

  125. Musgrave DS, Bosch P, Ghivizzani S, Robbins PD, Evans CH, Huard J. Bone 1999;24:541–547.

    Article  CAS  Google Scholar 

  126. Patel N, Padera R, Sanders GH, et al. FASEB J 1998;12:1447–1454.

    PubMed  CAS  Google Scholar 

  127. Pearson RG, Bhandari R, Quirk RA, Shakesheff KM. J Long Term Eff Med Implants 2002;12:1–33.

    PubMed  CAS  Google Scholar 

  128. Rezania A, Healy KE. J Orthop Res 1999;17:615–623.

    Article  PubMed  CAS  Google Scholar 

  129. Dee KC, Anderson TT, Bizios R. Biomaterials 1999;20:221–227.

    Article  PubMed  CAS  Google Scholar 

  130. Yang XB, Roach HI, Clarke NM, et al. Bone 2001;29:523–531.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Bone and Joint Research Group, Developmental Origins of Health and Disease, University of Southampton, S016 6YD, Southampton, UK

    Richard O. C. Oreffo & Cyrus Cooper

  2. The Advanced Centre for Biochemical Engineering, University College London, WC1E 7JE, London, UK

    Christopher Mason

  3. Cancer Research UK, Viral Oncology Group, Wolfson Institute for Biomedical Research, University College London, WC1E 6BT, London, UK

    Mark Clements

Authors
  1. Richard O. C. Oreffo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Cyrus Cooper
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Christopher Mason
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mark Clements
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Richard O. C. Oreffo.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Oreffo, R.O.C., Cooper, C., Mason, C. et al. Mesenchymal stem cells. Stem Cell Rev 1, 169–178 (2005). https://doi.org/10.1385/SCR:1:2:169

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1385/SCR:1:2:169

Index Entries

Search

Navigation