Stem Cell Reviews

, Volume 1, Issue 2, pp 169–178 | Cite as

Mesenchymal stem cells

Lineage, plasticity, and skeletal therapeutic potential
  • Richard O. C. Oreffo
  • Cyrus Cooper
  • Christopher Mason
  • Mark Clements
Original Article

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.

Index Entries

Osteoprogenitor bone regeneration cell therapy mesenchymal stem cell tissue engineering osteoblast marrow stromal cells regenerative medicine 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Ding S, Wu TY, Brinker A, et al. Proc Natl Acad Sci USA 2003;100:7632–7637.PubMedCrossRefGoogle Scholar
  2. 2.
    Wu X, Ding S, Ding Q, Gray NS, Schultz PG. J Am Chem Soc 2004;126:1590–1591.PubMedCrossRefGoogle Scholar
  3. 3.
    Gaspar HB, Howe S, Thrasher AJ. Gene Ther 2003;10:1999–2004.PubMedCrossRefGoogle Scholar
  4. 4.
    Hubel K, Engert A. Ann Hematol 2003;82:207–213.PubMedGoogle Scholar
  5. 5.
    Perin EC, Dohmann HF, Borojevic R, et al. Circulation 2003;107:2294–2302.PubMedCrossRefGoogle Scholar
  6. 6.
    Menasche P. Surg Clin North Am 2004;84:125–139.PubMedCrossRefGoogle Scholar
  7. 7.
    Friedenstein AJ, Petrakova KV, Kurolesova AI, Frolova GP. Transplantation 1968;6:230–247.PubMedCrossRefGoogle Scholar
  8. 8.
    Friedenstein AJ. Int Rev Cytol 1976;47:327–359.PubMedCrossRefGoogle Scholar
  9. 9.
    Friedenstein AJ, Ivanov-Smolenski AA, Chajlakjan RK, et al. Exp Hematol 1978;6:440–444.PubMedGoogle Scholar
  10. 10.
    Triffitt JT. J Cell Biochem Suppl 2002;38:13–19.PubMedCrossRefGoogle Scholar
  11. 11.
    Owen M, Friedenstein AJ. Ciba Found Symp 1988;136:42–60.PubMedGoogle Scholar
  12. 12.
    Goshima J, Goldberg VM, Caplan AI. Clin Orthop 1991;262:298–311.PubMedGoogle Scholar
  13. 13.
    Bianco P, Robey PG. Nature 2001;414:118–121.PubMedCrossRefGoogle Scholar
  14. 14.
    Lajtha LG. Differentiation 1979;14:23–34.PubMedCrossRefGoogle Scholar
  15. 15.
    Lovell-Badge R. Nature 2001;414:88–91.PubMedCrossRefGoogle Scholar
  16. 16.
    Bianco P, Riminucci M, Gronthos S, Robey PG. Stem Cells 2001;19:180–192.PubMedCrossRefGoogle Scholar
  17. 17.
    Jiang Y, Jahagirdar BN, Reinhardt RL, et al. Nature 2002;418:41–49.PubMedCrossRefGoogle Scholar
  18. 18.
    Verfaillie CM. Trends Cell Biol 2002;12:502–508.PubMedCrossRefGoogle Scholar
  19. 19.
    Pittenger MF, Mackay AM, Beck SC, et al. Science 1999;284:143–147.PubMedCrossRefGoogle Scholar
  20. 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. 21.
    Bruder SP, Horowitz MC, Mosca JD, Haynesworth SE. Bone 1997;21:225–235.PubMedCrossRefGoogle Scholar
  22. 22.
    Simmons PJ, Torok-Storb B. Blood 1991;78:2848–2853.PubMedGoogle Scholar
  23. 23.
    Gronthos S, Simmons PJ. Blood 1995;85:929–940.PubMedGoogle Scholar
  24. 24.
    Gronthos S, Zannettino AC, Graves SE, Ohta S, Hay SJ, Simmons PJ. J Bone Miner Res 1999;14:47–56.PubMedCrossRefGoogle Scholar
  25. 25.
    Haynesworth SE, Baber MA, Caplan AI. Bone 1992;13:69–80.PubMedCrossRefGoogle Scholar
  26. 26.
    Joyner CJ, Bennett A, Triffitt JT. Bone 1997;21:1–6.PubMedCrossRefGoogle Scholar
  27. 27.
    Gronthos S, Graves SE, Ohta S, Simmons PJ. Blood 1994;84:4164–4173.PubMedGoogle Scholar
  28. 28.
    Stewart K, Walsh S, Screen J, et al. J Bone Miner Res 1999;14:1345–1356.PubMedCrossRefGoogle Scholar
  29. 29.
    Howard D, Partridge K, Yang X, et al. Biochem Biophys Res Commun 2002;299:208–215.PubMedCrossRefGoogle Scholar
  30. 30.
    Bruder SP, Ricalton NS, Boynton RE, et al. J Bone Miner Res 1998;13:655–663.PubMedCrossRefGoogle Scholar
  31. 31.
    Barry FP, Boynton RE, Haynesworth S, Murphy JM, Zaia J. Biochem Biophys Res Commun 1999;265:134–139.PubMedCrossRefGoogle Scholar
  32. 32.
    Triffitt JT, Oreffo RO, Virdi AS, Xia Z. Cytotherapy 2001;3:413–416.PubMedCrossRefGoogle Scholar
  33. 33.
    Gronthos S, Zannettino AC, Hay SJ, et al. J Cell Sci 2003;116:1827–1835.PubMedCrossRefGoogle Scholar
  34. 34.
    Waller EK, Olweus J, Lund-Johansen F, et al. Blood 1995;85:2422–2435.PubMedGoogle Scholar
  35. 35.
    Jones EA, Kinsey SE, English A, et al. Arthritis Rheum 2002;46:3349–3360.PubMedCrossRefGoogle Scholar
  36. 36.
    Park SR, Oreffo RO, Triffitt JT. Bone 1999;24:549–554.PubMedCrossRefGoogle Scholar
  37. 37.
    Kuznetsov SA, Mankani MH, Gronthos S, Satomura K, Bianco P, Robey PG. J Cell Biol 2001;153:1133–1140.PubMedCrossRefGoogle Scholar
  38. 38.
    Friedenstein AJ, Deriglasova UF, Kulagina NN, et al. Exp Hematol 1974;2:83–92.PubMedGoogle Scholar
  39. 39.
    Triffitt JT, Oreffo ROC. In: Molecular and Cellular Biology of Bone (Zaidi M, ed.). JAI, CT: 1998;429–451.Google Scholar
  40. 40.
    Nuttall ME, Gimble JM. Bone 2000;27:177–184.PubMedCrossRefGoogle Scholar
  41. 41.
    Nuttall ME, Patton AJ, Olivera DL, Nadeau DP, Gowen M. J Bone Miner Res 1998;13:371–382.PubMedCrossRefGoogle Scholar
  42. 42.
    Krause DS. Gene Ther 2002;9:754–758.PubMedCrossRefGoogle Scholar
  43. 43.
    Ferrari G, Cusella-De Angelis G, Coletta M, et al. Science 1998;279:1528–1530.PubMedCrossRefGoogle Scholar
  44. 44.
    Sanchez-Ramos J, Song S, Cardozo-Pelaez F, et al. Exp Neurol 2000;164:247–256.PubMedCrossRefGoogle Scholar
  45. 45.
    Reyes M, Lund T, Lenvik T, Aguiar D, Koodie L, Verfaillie CM. Blood 2001;98:2615–2625.PubMedCrossRefGoogle Scholar
  46. 46.
    Reyes M, Dudek A, Jahagirdar B, Koodie L, Marker PH, Verfaillie CM. J Clin Invest 2002;109:337–346.PubMedCrossRefGoogle Scholar
  47. 47.
    Schwartz RE, Reyes M, Koodie L, et al. J Clin Invest 2002;109:1291–1302.PubMedCrossRefGoogle Scholar
  48. 48.
    Vassilopoulos G, Wang PR, Russell DW. Nature 2003;422:901–904.PubMedCrossRefGoogle Scholar
  49. 49.
    Wang X, Willenbring H, Akkari Y, et al. Nature 2003;422:897–901.PubMedCrossRefGoogle Scholar
  50. 50.
    Kuznetsov SA, Friedenstein AJ, Robey PG. Br J Haematol 1997;97:561–570.PubMedCrossRefGoogle Scholar
  51. 51.
    Oreffo RO, Romberg S, Virdi AS, Joyner CJ, Berven S, Triffitt JT. J Cell Biochem 1999;74:372–385.PubMedCrossRefGoogle Scholar
  52. 52.
    Walsh S, Jefferiss C, Stewart K, Jordan GR, Screen J, Beresford JN. Bone 2000;27:185–195.PubMedCrossRefGoogle Scholar
  53. 53.
    Tsutsumi S, Shimazu A, Miyazaki K, et al. Biochem Biophys Res Commun 2001;288:413–419.PubMedCrossRefGoogle Scholar
  54. 54.
    Martin I, Muraglia A, Campanile G, Cancedda R, Quarto R. Endocrinology 1997;138:4456–4462.PubMedCrossRefGoogle Scholar
  55. 55.
    Wozney JM, Rosen V. Clin Orthop 1998;346:26–37.PubMedGoogle Scholar
  56. 56.
    Chen D, Ji X, Harris MA, et al. J Cell Biol 1998;142:295–305.PubMedCrossRefGoogle Scholar
  57. 57.
    Pfeilschifter J, Wolf O, Naumann A, Minne HW, Mundy GR, Ziegler R. J Bone Miner Res 1990;5:825–830.PubMedGoogle Scholar
  58. 58.
    Locklin RM, Oreffo RO, Triffitt JT. Cell Biol Int 1999;23:185–194.PubMedCrossRefGoogle Scholar
  59. 59.
    Walsh S, Jefferiss C, Stewart K, Beresford JN. Cell Tissue Res 2003;311:187–198.PubMedGoogle Scholar
  60. 60.
    Wang EA, Israel DI, Kelly S, Luxenberg DP. Growth Factors 1993;9:57–71.PubMedGoogle Scholar
  61. 61.
    Rickard DJ, Sullivan TA, Shenker BJ, Leboy PS, Kazhdan I. Dev Biol 1994;161:218–228.PubMedCrossRefGoogle Scholar
  62. 62.
    Locklin RM, Williamson MC, Beresford JN, Triffitt JT, Owen ME. Clin Orthop 1995;313:27–35.PubMedGoogle Scholar
  63. 63.
    Oreffo RO, Virdi AS, Triffitt JT. Eur J Cell Biol 1997;74:251–261.PubMedGoogle Scholar
  64. 64.
    Cheng SL, Yang JW, Rifas L, Zhang SF, Avioli LV. Endocrinology 1994;134:277–286.PubMedCrossRefGoogle Scholar
  65. 65.
    Kimoto S, Cheng SL, Zhang SF, Avioli LV. Endocrinology 1994;135:2423–2431.PubMedCrossRefGoogle Scholar
  66. 66.
    Walsh S, Jordan GR, Jefferiss C, Stewart K, Beresford JN. Rheumatology (Oxford) 2001;40:74–83.CrossRefGoogle Scholar
  67. 67.
    Beresford JN, Joyner CJ, Devlin C, Triffitt JT. Arch Oral Biol 1994;39:941–947.PubMedCrossRefGoogle Scholar
  68. 68.
    Scutt A, Bertram P. J Bone Miner Res 1995;10:474–487.PubMedGoogle Scholar
  69. 69.
    Still K, Scutt A. Prostaglandins Other Lipid Mediat 2001;65:21–31.PubMedCrossRefGoogle Scholar
  70. 70.
    Kasugai S, Oida S, Iimura T, et al. Bone 1995;17:1–4.PubMedCrossRefGoogle Scholar
  71. 71.
    Oreffo ROC, Wells N, Johnstone D. J Bone Miner Res 1991;6:S208.Google Scholar
  72. 72.
    Yang X, Tare RS, Partridge KA, et al. J Bone Miner Res 2003;18:47–57.PubMedCrossRefGoogle Scholar
  73. 73.
    Tare RS, Oreffo RO, Clarke NM, Roach HI. J Bone Miner Res 2002;17:2009–2020.PubMedCrossRefGoogle Scholar
  74. 74.
    Jilka RL. Bone 1998;23:75–81.PubMedCrossRefGoogle Scholar
  75. 75.
    Manolagas SC, Jilka RL. N Engl J Med 1995;332:305–311.PubMedCrossRefGoogle Scholar
  76. 76.
    Boyce BF, Aufdemorte TB, Garrett IR, Yates AJ, Mundy GR. Endocrinology 1989;125:1142–1150.PubMedCrossRefGoogle Scholar
  77. 77.
    Nishida S, Endo N, Yamagiwa H, Tanizawa T, Takahashi HE. J Bone Miner Metab 1999;17:171–177.PubMedCrossRefGoogle Scholar
  78. 78.
    D’Ippolito G, Schiller PC, Ricordi C, Roos BA, Howard GA. J Bone Miner Res 1999;14:1115–1122.PubMedCrossRefGoogle Scholar
  79. 79.
    Majors AK, Boehm CA, Nitto H, Midura RJ, Muschler GF. J Orthop Res 1997;15:546–557.PubMedCrossRefGoogle Scholar
  80. 80.
    Egrise D, Martin D, Vienne A, Neve P, Schoutens A. Bone 1992;13:355–361.PubMedCrossRefGoogle Scholar
  81. 81.
    Bergman RJ, Gazit D, Kahn AJ, Gruber H, McDougall S, Hahn TJ. J Bone Miner Res 1996;11:568–577.PubMedGoogle Scholar
  82. 82.
    Oreffo RO, Bennett A, Carr AJ, Triffitt JT. Scand J Rheumatol 1998;27:415–424.PubMedCrossRefGoogle Scholar
  83. 83.
    Oreffo RO, Bord S, Triffitt JT. Clin Sci (Colch) 1998;94:549–555.Google Scholar
  84. 84.
    Marcotte R, Wang E. J Gerontol A Biol Sci Med Sci 2002;57:B257-B269.PubMedGoogle Scholar
  85. 85.
    Pedro De MJ. Exp Cell Res 2004;300:1–10.CrossRefGoogle Scholar
  86. 86.
    Zimmermann S, Voss M, Kaiser S, Kapp U, Waller CF, Martens UM. Leukemia 2003;17:1146–1149.PubMedCrossRefGoogle Scholar
  87. 87.
    Okamoto T, Aoyama T, Nakayama T, et al. Biochem Biophys Res Commun 2002;295:354–361.PubMedCrossRefGoogle Scholar
  88. 88.
    Shi S, Gronthos S, Chen S, et al. Nat Biotechnol 2002;20:587–591.PubMedCrossRefGoogle Scholar
  89. 89.
    Simonsen JL, Rosada C, Serakinci N, et al. Nat Biotechnol 2002;20:592–596.PubMedCrossRefGoogle Scholar
  90. 90.
    Serakinci N, Guldberg P, Burns JS, et al. Oncogene 2004;23:5095–5098.PubMedCrossRefGoogle Scholar
  91. 91.
    Stenderup K, Justesen J, Eriksen EF, Rattan SI, Kassem M. J Bone Miner Res 2001;16:1120–1129.PubMedCrossRefGoogle Scholar
  92. 92.
    Pfeilschifter J, Diel I, Pilz U, Brunotte K, Naumann A, Ziegler R. J Bone Miner Res 1993;8:707–717.PubMedGoogle Scholar
  93. 93.
    Erdmann J, Kogler C, Diel I, Ziegler R, Pfeilschifter J. Mech Ageing Dev 1999;110:73–85.PubMedCrossRefGoogle Scholar
  94. 94.
    [No authors listed]. Am J Med 1993;94:646–650.Google Scholar
  95. 95.
    Melton LJ, III, Chrischilles EA, Cooper C, Lane AW, Riggs BL. J Bone Miner Res 1992;7:1005–1010.PubMedCrossRefGoogle Scholar
  96. 96.
    Cooper C. Am J Med 1997;103:12S-17S.PubMedCrossRefGoogle Scholar
  97. 97.
    Christodoulou C, Cooper C. Postgrad Med J 2003;79:133–138.PubMedCrossRefGoogle Scholar
  98. 98.
    Spector M. Orthop Clin North Am 1992;23:211–217.PubMedGoogle Scholar
  99. 99.
    Rose FR, Oreffo RO. Biochem Biophys Res Commun 2002;292:1–7.PubMedCrossRefGoogle Scholar
  100. 100.
    Langer R, Vacanti JP. Science 1993;260:920–926.PubMedCrossRefGoogle Scholar
  101. 101.
    Kadiyala S, Young RG, Thiede MA, Bruder SP. Cell Transplant 1997;6:125–134.PubMedCrossRefGoogle Scholar
  102. 102.
    Gundle R, Joyner CJ, Triffitt JT. Bone 1995;16:597–601.PubMedCrossRefGoogle Scholar
  103. 103.
    Nakahara H, Bruder SP, Haynesworth SE, et al. Bone 1990;11:181–188.PubMedCrossRefGoogle Scholar
  104. 104.
    Ohgushi H, Goldberg VM, Caplan AI. J Orthop Res 1989;7:568–578.PubMedCrossRefGoogle Scholar
  105. 105.
    Simmons PJ, Torok-Storb B. Blood 1991;78:55–62.PubMedGoogle Scholar
  106. 106.
    Stewart K, Walsh S, Screen J, et al. J Bone Miner Res 1999;14:1345–1356.PubMedCrossRefGoogle Scholar
  107. 107.
    Bruder SP, Jaiswal N, Haynesworth SE. J Cell Biochem 1997;64:278–294.PubMedCrossRefGoogle Scholar
  108. 108.
    Jaiswal N, Haynesworth SE, Caplan AI, Bruder SP. J Cell Biochem 1997;64:295–312.PubMedCrossRefGoogle Scholar
  109. 109.
    Bartholomew A, Sturgeon C, Siatskas M, et al. Exp Hematol 2002;30:42–48.PubMedCrossRefGoogle Scholar
  110. 110.
    Di Nicola M, Carlo-Stella C, Magni M, et al. Blood 2002;99:3838–3843.PubMedCrossRefGoogle Scholar
  111. 111.
    Arinzeh TL, Peter SJ, Archambault MP, et al. J Bone Joint Surg Am 2003;85A:1927–1935.Google Scholar
  112. 112.
    Horwitz EM, Prockop DJ, Fitzpatrick LA, et al. Nat Med 1999;5:309–313.PubMedCrossRefGoogle Scholar
  113. 113.
    Horwitz EM, Prockop DJ, Gordon PL, et al. Blood 2001;97:1227–1231.PubMedCrossRefGoogle Scholar
  114. 114.
    Dominici M, Hofmann TJ, Horwitz EM. J Biol Regul Homeost Agents 2001;15:28–37.PubMedGoogle Scholar
  115. 115.
    Connolly JF. Clin Orthop 1995;313:8–18.PubMedGoogle Scholar
  116. 116.
    Quarto R, Mastrogiacomo M, Cancedda R, et al. N Engl J Med 2001;344:385–386.PubMedCrossRefGoogle Scholar
  117. 117.
    Perry CR. Clin Orthop 1999;360:71–86.PubMedCrossRefGoogle Scholar
  118. 118.
    Boden SD. Clin Orthop 1999;367:S84-S94.PubMedCrossRefGoogle Scholar
  119. 119.
    Oreffo RO, Triffitt JT. Bone 1999;25:5S-9S.PubMedCrossRefGoogle Scholar
  120. 120.
    Lieberman JR, Daluiski A, Stevenson S, et al. J Bone Joint Surg Am 1999;81:905–917.PubMedGoogle Scholar
  121. 121.
    Breitbart AS, Grande DA, Mason JM, Barcia M, James T, Grant RT. Ann Plast Surg 1999;42:488–495.PubMedCrossRefGoogle Scholar
  122. 122.
    Olmsted EA, Blum JS, Rill D, et al. J Cell Biochem 2001;82:11–21.PubMedCrossRefGoogle Scholar
  123. 123.
    Turgeman G, Pittman DD, Muller R, et al. J Gene Med 2001;3:240–251.PubMedCrossRefGoogle Scholar
  124. 124.
    Partridge K, Yang X, Clarke NM, et al. Biochem Biophys Res Commun 2002;292:144–152.PubMedCrossRefGoogle Scholar
  125. 125.
    Musgrave DS, Bosch P, Ghivizzani S, Robbins PD, Evans CH, Huard J. Bone 1999;24:541–547.CrossRefGoogle Scholar
  126. 126.
    Patel N, Padera R, Sanders GH, et al. FASEB J 1998;12:1447–1454.PubMedGoogle Scholar
  127. 127.
    Pearson RG, Bhandari R, Quirk RA, Shakesheff KM. J Long Term Eff Med Implants 2002;12:1–33.PubMedGoogle Scholar
  128. 128.
    Rezania A, Healy KE. J Orthop Res 1999;17:615–623.PubMedCrossRefGoogle Scholar
  129. 129.
    Dee KC, Anderson TT, Bizios R. Biomaterials 1999;20:221–227.PubMedCrossRefGoogle Scholar
  130. 130.
    Yang XB, Roach HI, Clarke NM, et al. Bone 2001;29:523–531.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc. 2005

Authors and Affiliations

  • Richard O. C. Oreffo
    • 1
  • Cyrus Cooper
    • 1
  • Christopher Mason
    • 2
  • Mark Clements
    • 3
  1. 1.Bone and Joint Research Group, Developmental Origins of Health and DiseaseUniversity of SouthamptonSouthamptonUK
  2. 2.The Advanced Centre for Biochemical EngineeringUniversity College LondonLondonUK
  3. 3.Cancer Research UK, Viral Oncology Group, Wolfson Institute for Biomedical ResearchUniversity College LondonLondonUK

Personalised recommendations