Bone Cement pp 43-68 | Cite as

Productivity: Cells

  • Hamid Reza RezaieEmail author
  • Mohammad Hossein Esnaashary
  • Masoud Karfarma
  • Andreas Öchsner
Part of the SpringerBriefs in Applied Sciences and Technology book series (BRIEFSAPPLSCIENCES)


In tissue engineering, besides osteoconductivity and osteoinductivity, the ability to regenerate tissue should also be considered. To this aim, many kinds of cells have been investigated to seed on scaffolds. Bone tissue is a habitat of various kinds of the cells dividing into two main categories: stem cell niches and resident cells in bone. The latter includes osteoblasts, osteoclasts, osteocytes, and osteoprogenitor cells. According to these cells, four classes of the stem cells and their derivations have been selected to be used in the bone tissue engineering. The classes discussed in this chapter are as follows: embryonic stem cells, induced pluripotent stem cells, fetal stem cells, and adult stem cells. Besides the kinds of cells, the methods for seeding the cells and the reactors for enhancement of the cell activities are also important, which are explained at the end of this chapter.


  1. 1.
    O. Shinsuke, Y. Fumiko, C. Ung-il, Tissue engineering of bone and cartilage. IBMS Bonekey. 6, 405–419 (2009)CrossRefGoogle Scholar
  2. 2.
    A.R. Amini, C.T. Laurencin, S.P. Nukavarapu, Bone tissue engineering: recent advances and challenges. Crit. Rev. Biomed. Eng. 40, 363–408 (2012). Scholar
  3. 3.
    I. Drosse, E. Volkmer, R. Capanna, P. De Biase, W. Mutschler, M. Schieker, Tissue engineering for bone defect healing: an update on a multi-component approach. Injury 39, S9–S20 (2008). Scholar
  4. 4.
    P.G. Robey, Cell sources for bone regeneration: the good, the bad, and the ugly (but promising). Tissue Eng. Part B Rev. 17, 423–430 (2011). Scholar
  5. 5.
    T. Yin, L. Li, The stem cell niches in bone. J. Clin. Invest. 116, 1195–1201 (2006). Scholar
  6. 6.
    D. Lopes, C. Martins-Cruz, M.B. Oliveira, J.F. Mano, Bone physiology as inspiration for tissue regenerative therapies. Biomaterials 185, 240–275 (2018). Scholar
  7. 7.
    R. Nerem, A. Atala, R. Lanza, T. Mikos, Stem cells derived from amniotic fluid and placenta, in Principles of Regenerative Medicine (Academic Press, London, 2008), p. 1472Google Scholar
  8. 8.
    R. Florencio-Silva, G.R.D.S. Sasso, E. Sasso-Cerri, M.J. Simões, P.S. Cerri, Biology of bone tissue: structure, function, and factors that influence bone cells. Biomed. Res. Int. 2015, 1–17 (2015). Scholar
  9. 9.
    M. Capulli, R. Paone, N. Rucci, Osteoblast and osteocyte: games without frontiers. Arch. Biochem. Biophys. 561, 3–12 (2014). Scholar
  10. 10.
    K.A. Young, J.A. Wise, P. DeSaix, D.H. Kruse, B. Poe, E. Johnson, J.E. Johnson, O. Korol, J.G. Betts, M. Womble, Anatomy and Physiology, 1st edn. (Houston, Texas, USA, 2013)Google Scholar
  11. 11.
    B. Clarke, Normal bone anatomy and physiology. Clin. J. Am. Soc. Nephrol. 3, S131–S139 (2008). Scholar
  12. 12.
    K. Matsuo, Cross-talk among bone cells. Curr. Opin. Nephrol. Hypertens. 18, 292–297 (2009). Scholar
  13. 13.
    F. Martini, J.L. Nath, E.F. Bartholomew, Fundamentals of Anatomy & Physiology (Essex, England, 2015)Google Scholar
  14. 14.
    M. Tang, W. Chen, M.D. Weir, W. Thein-Han, H.H.K. Xu, Human embryonic stem cell encapsulation in alginate microbeads in macroporous calcium phosphate cement for bone tissue engineering. Acta Biomater. 8, 3436–3445 (2012). Scholar
  15. 15.
    M. Meregalli, A. Farini, Y. Torrente, Stem cell therapy for neuromuscular diseases, in Stem Cells in Clinic and Research (InTech, 2011). Scholar
  16. 16.
    S. Kargozar, M. Mozafari, S. Hamzehlou, P. Brouki Milan, H.-W. Kim, F. Baino, Bone tissue engineering using human cells: a comprehensive review on recent trends, current prospects, and recommendations. Appl. Sci. 9, 174 (2019). Scholar
  17. 17.
    A.-M. Yousefi, P.F. James, R. Akbarzadeh, A. Subramanian, C. Flavin, H. Oudadesse, Prospect of stem cells in bone tissue engineering: a review. Stem Cells Int. 2016, 1–13 (2016). Scholar
  18. 18.
    W. Chen, H. Zhou, M.D. Weir, M. Tang, C. Bao, H.H.K. Xu, Human embryonic stem cell-derived mesenchymal stem cell seeding on calcium phosphate cement-chitosan-RGD scaffold for bone repair. Tissue Eng. Part A 19, 915–927 (2013). Scholar
  19. 19.
    X. Liu, P. Wang, W. Chen, M.D. Weir, C. Bao, H.H.K. Xu, Human embryonic stem cells and macroporous calcium phosphate construct for bone regeneration in cranial defects in rats. Acta Biomater. 10, 4484–4493 (2014). Scholar
  20. 20.
    L. Wang, P. Wang, M.D. Weir, M.A. Reynolds, L. Zhao, H.H.K. Xu, Hydrogel fibers encapsulating human stem cells in an injectable calcium phosphate scaffold for bone tissue engineering. Biomed. Mater. 11, 065008 (2016). Scholar
  21. 21.
    Y. Lin, S. Huang, R. Zou, X. Gao, J. Ruan, M.D. Weir, M.A. Reynolds, W. Qin, X. Chang, H. Fu, H.H.K. Xu, Calcium phosphate cement scaffold with stem cell co-culture and prevascularization for dental and craniofacial bone tissue engineering. Dent. Mater. 35, 1031–1041 (2019). Scholar
  22. 22.
    S. Yamanaka, H.M. Blau, Nuclear reprogramming to a pluripotent state by three approaches. Nature 465, 704–712 (2010). Scholar
  23. 23.
    J. Liu, W. Chen, Z. Zhao, H.H.K. Xu, Reprogramming of mesenchymal stem cells derived from iPSCs seeded on biofunctionalized calcium phosphate scaffold for bone engineering. Biomaterials 34, 7862–7872 (2013). Scholar
  24. 24.
    M. Tang, W. Chen, J. Liu, M.D. Weir, L. Cheng, H.H.K. Xu, Human induced pluripotent stem cell-derived mesenchymal stem cell seeding on calcium phosphate scaffold for bone regeneration. Tissue Eng. Part A 20, 1295–1305 (2014). Scholar
  25. 25.
    W. TheinHan, J. Liu, M. Tang, W. Chen, L. Cheng, H.H.K. Xu, Induced pluripotent stem cell-derived mesenchymal stem cell seeding on biofunctionalized calcium phosphate cements. Bone Res. 1, 371–384 (2013). Scholar
  26. 26.
    P. Wang, X. Liu, L. Zhao, M.D. Weir, J. Sun, W. Chen, Y. Man, H.H.K. Xu, Bone tissue engineering via human induced pluripotent, umbilical cord and bone marrow mesenchymal stem cells in rat cranium. Acta Biomater. 18, 236–248 (2015). Scholar
  27. 27.
    M. Sladkova, M. Palmer, C. Öhman, R.J. Alhaddad, A. Esmael, H. Engqvist, G.M. de Peppo, Fabrication of macroporous cement scaffolds using PEG particles: in vitro evaluation with induced pluripotent stem cell-derived mesenchymal progenitors. Mater. Sci. Eng., C 69, 640–652 (2016). Scholar
  28. 28.
    M. Sladkova, M. Palmer, C. Öhman, J. Cheng, S. Al-Ansari, M. Saad, H. Engqvist, G.M. de Peppo, Engineering human bone grafts with new macroporous calcium phosphate cement scaffolds. J. Tissue Eng. Regen. Med. 12, 715–726 (2018). Scholar
  29. 29.
    X. Liu, W. Chen, C. Zhang, W. Thein-Han, K. Hu, M.A. Reynolds, C. Bao, P. Wang, L. Zhao, H.H.K. Xu, Co-seeding human endothelial cells with human-induced pluripotent stem cell-derived mesenchymal stem cells on calcium phosphate scaffold enhances osteogenesis and vascularization in rats. Tissue Eng. Part A 23, 546–555 (2017). Scholar
  30. 30.
    R.P. Dorin, C.J. Koh, Fetal tissues, in Principles of Regenerative Medicine (Elsevier, 2011), pp. 819–832. Scholar
  31. 31.
    C. Molnar, J. Gair, Human pregnancy and birth, in Concepts of Biology, 1st edn. (Houston, Texas, USA, 2013)Google Scholar
  32. 32.
    A.J. Wagers, I.L. Weissman, Plasticity of adult stem cells. Cell 116, 639–648 (2004). Scholar
  33. 33.
    A.H. Undale, J.J. Westendorf, M.J. Yaszemski, S. Khosla, Mesenchymal stem cells for bone repair and metabolic bone diseases. Mayo Clin. Proc. 84, 893–902 (2009). Scholar
  34. 34.
    H. Xia, X. Li, W. Gao, X. Fu, R.H. Fang, L. Zhang, K. Zhang, Tissue repair and regeneration with endogenous stem cells. Nat. Rev. Mater. 3, 174–193 (2018). Scholar
  35. 35.
    A. Uccelli, L. Moretta, V. Pistoia, Mesenchymal stem cells in health and disease. Nat. Rev. Immunol. 8, 726–736 (2008). Scholar
  36. 36.
    M.D. Weir, H.H.K. Xu, Culture human mesenchymal stem cells with calcium phosphate cement scaffolds for bone repair, J. Biomed. Mater. Res. Part B Appl. Biomater. 93B, 93–105 (2010). Scholar
  37. 37.
    M.D. Weir, H.H.K. Xu, Human bone marrow stem cell-encapsulating calcium phosphate scaffolds for bone repair. Acta Biomater. 6, 4118–4126 (2010). Scholar
  38. 38.
    T. Liu, J. Li, Z. Shao, K. Ma, Z. Zhang, B. Wang, Y. Zhang, Encapsulation of mesenchymal stem cells in chitosan/β-glycerophosphate hydrogel for seeding on a novel calcium phosphate cement scaffold. Med. Eng. Phys. 56, 9–15 (2018). Scholar
  39. 39.
    W. Chen, J. Liu, N. Manuchehrabadi, M.D. Weir, Z. Zhu, H.H.K. Xu, Umbilical cord and bone marrow mesenchymal stem cell seeding on macroporous calcium phosphate for bone regeneration in rat cranial defects. Biomaterials 34, 9917–9925 (2013). Scholar
  40. 40.
    G. Qiu, Z. Shi, H.H.K. Xu, B. Yang, M.D. Weir, G. Li, Y. Song, J. Wang, K. Hu, P. Wang, L. Zhao, Bone regeneration in minipigs via calcium phosphate cement scaffold delivering autologous bone marrow mesenchymal stem cells and platelet-rich plasma. J. Tissue Eng. Regen. Med. 12, e937–e948 (2018). Scholar
  41. 41.
    J. Pak, J.H. Lee, K.S. Park, M. Park, L.-W. Kang, S.H. Lee, Current use of autologous adipose tissue-derived stromal vascular fraction cells for orthopedic applications. J. Biomed. Sci. 24, 9 (2017). Scholar
  42. 42.
    S. Kern, H. Eichler, J. Stoeve, H. Klüter, K. Bieback, Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue. Stem Cells 24, 1294–1301 (2006). Scholar
  43. 43.
    Y. Zhu, T. Liu, K. Song, X. Fan, X. Ma, Z. Cui, Adipose-derived stem cell: a better stem cell than BMSC. Cell Biochem. Funct. 26, 664–675 (2008). Scholar
  44. 44.
    Y. Alabdulkarim, B. Ghalimah, M. Al-Otaibi, H. Al-Jallad, M. Mekhael, B. Willie, R. Hamdy, Recent advances in bone regeneration: the role of adipose tissue-derived stromal vascular fraction and mesenchymal stem cells. J. Limb Lengthening Reconstr. 3, 4 (2017). Scholar
  45. 45.
    R.T. Qomi, M. Sheykhhasan, Adipose-derived stromal cell in regenerative medicine: a review. World J. Stem Cells 9, 107 (2017). Scholar
  46. 46.
    L. Shukla, W.A. Morrison, R. Shayan, Adipose-derived stem cells in radiotherapy injury: a new frontier. Front. Surg. 2 (2015).
  47. 47.
    J.T. Walker, A. Keating, J.E. Davies, Stem cells: umbilical cord/Wharton’s jelly derived, in Cell Engineering and Regeneration (Springer International Publishing, Cham, 2019), pp. 1–28. Scholar
  48. 48.
    D.-C. Ding, Y.-H. Chang, W.-C. Shyu, S.-Z. Lin, Human umbilical cord mesenchymal stem cells: a new era for stem cell therapy. Cell Transplant. 24, 339–347 (2015). Scholar
  49. 49.
    T. Nagamura-Inoue, Umbilical cord-derived mesenchymal stem cells: their advantages and potential clinical utility. World J. Stem Cells. 6, 195 (2014). Scholar
  50. 50.
    H. Zhou, M.D. Weir, H.H.K. Xu, Effect of cell seeding density on proliferation and osteodifferentiation of umbilical cord stem cells on calcium phosphate cement-fiber scaffold. Tissue Eng. Part A 17, 2603–2613 (2011). Scholar
  51. 51.
    C. Bao, W. Chen, M.D. Weir, W. Thein-Han, H.H.K. Xu, Effects of electrospun submicron fibers in calcium phosphate cement scaffold on mechanical properties and osteogenic differentiation of umbilical cord stem cells. Acta Biomater. 7, 4037–4044 (2011). Scholar
  52. 52.
    W. Chen, H. Zhou, M. Tang, M.D. Weir, C. Bao, H.H.K. Xu, Gas-foaming calcium phosphate cement scaffold encapsulating human umbilical cord stem cells. Tissue Eng. Part A 18, 816–827 (2012). Scholar
  53. 53.
    W. Chen, H. Zhou, M.D. Weir, C. Bao, H.H.K. Xu, Umbilical cord stem cells released from alginate–fibrin microbeads inside macroporous and biofunctionalized calcium phosphate cement for bone regeneration. Acta Biomater. 8, 2297–2306 (2012). Scholar
  54. 54.
    W. Thein-Han, H.H.K. Xu, Collagen-calcium phosphate cement scaffolds seeded with umbilical cord stem cells for bone tissue engineering. Tissue Eng. Part A 17, 2943–2954 (2011). Scholar
  55. 55.
    G.T.-J. Huang, S. Gronthos, S. Shi, Mesenchymal stem cells derived from dental tissues vs. those from other sources: their biology and role in regenerative medicine. J. Dent. Res. 88, 792–806 (2009). Scholar
  56. 56.
    H. Egusa, W. Sonoyama, M. Nishimura, I. Atsuta, K. Akiyama, Stem cells in dentistry—Part I: stem cell sources. J. Prosthodont. Res. 56, 151–165 (2012). Scholar
  57. 57.
    M.B. Eslaminejad, S. Bordbar, H. Nazarian, Odontogenic differentiation of dental pulp-derived stem cells on tricalcium phosphate scaffolds. J. Dent. Sci. 8, 306–313 (2013). Scholar
  58. 58.
    W. Qin, J.-Y. Chen, J. Guo, T. Ma, M.D. Weir, D. Guo, Y. Shu, Z.-M. Lin, A. Schneider, H.H.K. Xu, Novel calcium phosphate cement with metformin-loaded chitosan for odontogenic differentiation of human dental pulp cells. Stem Cells Int. 2018, 1–10 (2018). Scholar
  59. 59.
    C. Ferretti, Periosteum derived stem cells for regenerative medicine proposals: boosting current knowledge. World J. Stem Cells. 6, 266 (2014). Scholar
  60. 60.
    J. Fan, R.R. Varshney, L. Ren, D. Cai, D.-A. Wang, Synovium-derived mesenchymal stem cells: a new cell source for musculoskeletal regeneration. Tissue Eng. Part B Rev. 15, 75–86 (2009). Scholar
  61. 61.
    D. McGonagle, T.G. Baboolal, E. Jones, Native joint-resident mesenchymal stem cells for cartilage repair in osteoarthritis. Nat. Rev. Rheumatol. 13, 719–730 (2017). Scholar
  62. 62.
    A. Usas, J. Huard, Muscle-derived stem cells for tissue engineering and regenerative therapy 28, 5401–5406 (2007)Google Scholar
  63. 63.
    E.J. Mackie, Osteoblasts: novel roles in orchestration of skeletal architecture. Int. J. Biochem. Cell Biol. 35, 1301–1305 (2003). Scholar
  64. 64.
    P. Jayakumar, L. Di Silvio, Osteoblasts in bone tissue engineering. Proc. Inst. Mech. Eng. Part H J. Eng. Med. 224, 1415–1440 (2010). Scholar
  65. 65.
    D. Han, Q. Zhang, An essential requirement for osteoclasts in refined bone-like tissue reconstruction in vitro. Med. Hypotheses 67, 75–78 (2006). Scholar
  66. 66.
    M.S. Rahman, N. Akhtar, H.M. Jamil, R.S. Banik, S.M. Asaduzzaman, TGF-β/BMP signaling and other molecular events: regulation of osteoblastogenesis and bone formation. Bone Res. 3, 15005 (2015). Scholar
  67. 67.
    S. Midha, W. van den Bergh, T.B. Kim, P.D. Lee, J.R. Jones, C.A. Mitchell, Bioactive glass foam scaffolds are remodelled by osteoclasts and support the formation of mineralized matrix and vascular networks in vitro. Adv. Healthc. Mater. 2, 490–499 (2013). Scholar
  68. 68.
    M. Baghaban, F. Faghihi, Mesenchymal stem cell-based bone engineering for bone regeneration, in Regenerative Medicine and Tissue EngineeringCells and Biomaterials (InTech, 2011). Scholar
  69. 69.
    J. Lott, P.H. de Carvalho, D. Assis, A.M. de Goes, Innovative strategies for tissue engineering, in Advances in Biomaterials Science and Biomedical Applications (InTech, 2013). Scholar
  70. 70.
    D.W. Hutmacher, H. Singh, Computational fluid dynamics for improved bioreactor design and 3D culture. Trends Biotechnol. 26, 166–172 (2008). Scholar
  71. 71.
    M. Sladkova, G. de Peppo, Bioreactor systems for human bone tissue engineering. Processes 2, 494–525 (2014). Scholar
  72. 72.
    I. Martin, D. Wendt, M. Heberer, The role of bioreactors in tissue engineering. Trends Biotechnol. 22, 80–86 (2004). Scholar
  73. 73.
    K.J. Blose, J.T. Krawiec, J.S. Weinbaum, D.A. Vorp, Bioreactors for tissue engineering purposes, in Regenerative Medicine Applications in Organ Transplantation (Elsevier, 2014), pp. 177–185. Scholar
  74. 74.
    N. Plunkett, F.J. O’Brien, IV.3. Bioreactors in tissue engineering. Stud. Health Technol. Inform. 152, 214–230 (2010)Google Scholar
  75. 75.
    N. Wung, S.M. Acott, D. Tosh, M.J. Ellis, Hollow fibre membrane bioreactors for tissue engineering applications. Biotechnol. Lett. 36, 2357–2366 (2014). Scholar
  76. 76.
    D.A. Gaspar, V. Gomide, F.J. Monteiro, The role of perfusion bioreactors in bone tissue engineering. Biomatter 2, 167–175 (2012). Scholar
  77. 77.
    A.J. El Haj, S.H. Cartmell, Bioreactors for bone tissue engineering. Proc. Inst. Mech. Eng. Part H J. Eng. Med. 224, 1523–1532 (2010). Scholar

Copyright information

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2020

Authors and Affiliations

  • Hamid Reza Rezaie
    • 1
    Email author
  • Mohammad Hossein Esnaashary
    • 1
  • Masoud Karfarma
    • 1
  • Andreas Öchsner
    • 2
  1. 1.Ceramic and Biomaterial Division, Department of Engineering MaterialsIran University of Science and TechnologyTehranIran
  2. 2.Faculty of Mechanical EngineeringEsslingen University of Applied SciencesEsslingen am NeckarGermany

Personalised recommendations