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Stem Cells in Bone Regeneration

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Abstract

Bone has the capacity to regenerate and repair itself. However, this capacity may be impaired or lost depending on the size of the defect or the presence of certain disease states. In this review, we discuss the key principles underlying bone healing, efforts to characterize bone stem and progenitor cell populations, and the current status of translational and clinical studies in cell-based bone tissue engineering. Though barriers to clinical implementation still exist, the application of stem and progenitor cell populations to bone engineering strategies has the potential to profoundly impact regenerative medicine.

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References

  1. Galen (1997). The usefulness of parts of the body. Clinical Orthopaedics and Related Research, 337, 3–12.

    Article  PubMed  Google Scholar 

  2. Howship, J. (1816). Microscopic observations on the structure of bone. Medico-chirurgical transactions, 7(382–592), 311.

    Google Scholar 

  3. Zhang, J., et al. (2003). Identification of the haematopoietic stem cell niche and control of the niche size. Nature, 425(6960), 836–841.

    Article  CAS  PubMed  Google Scholar 

  4. Calvi, L. M., et al. (2003). Osteoblastic cells regulate the haematopoietic stem cell niche. Nature, 425(6960), 841–846.

    Article  CAS  PubMed  Google Scholar 

  5. Ding, L., & Morrison, S. J. (2013). Haematopoietic stem cells and early lymphoid progenitors occupy distinct bone marrow niches. Nature, 495(7440), 231–235.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Zhou, B. O., Yue, R., Murphy, M. M., Peyer, J. G., & Morrison, S. J. (2014). Leptin-receptor-expressing mesenchymal stromal cells represent the main source of bone formed by adult bone marrow. Cell Stem Cell, 15(2), 154–168.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Cheloha, R. W., Gellman, S. H., Vilardaga, J. P., & Gardella, T. J. (2015). PTH receptor-1 signalling-mechanistic insights and therapeutic prospects. Nature reviews. Endocrinology, 11(12), 712–724.

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Rinkevich, Y., Lindau, P., Ueno, H., Longaker, M. T., & Weissman, I. L. (2011). Germ-layer and lineage-restricted stem/progenitors regenerate the mouse digit tip. Nature, 476(7361), 409–413.

    Article  CAS  PubMed  Google Scholar 

  9. Chan, C. K., et al. (2015). Identification and specification of the mouse skeletal stem cell. Cell, 160(1–2), 285–298.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Worthley, D. L., et al. (2015). Gremlin 1 identifies a skeletal stem cell with bone, cartilage, and reticular stromal potential. Cell, 160(1–2), 269–284.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Marecic, O., et al. (2015). Identification and characterization of an injury-induced skeletal progenitor. Proceedings of the National Academy of Sciences of the United States of America, 112(32), 9920–9925.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Rho, J. Y., Kuhn-Spearing, L., & Zioupos, P. (1998). Mechanical properties and the hierarchical structure of bone. Medical Engineering & Physics, 20(2), 92–102.

    Article  CAS  Google Scholar 

  13. Wang, Y., et al. (2012). The predominant role of collagen in the nucleation, growth, structure and orientation of bone apatite. Nature Materials, 11(8), 724–733.

    Article  CAS  PubMed  Google Scholar 

  14. Olsen, B. R., Reginato, A. M., & Wang, W. (2000). Bone development. Annual Review of Cell and Developmental Biology, 16, 191–220.

    Article  CAS  PubMed  Google Scholar 

  15. Nah, H. D., Pacifici, M., Gerstenfeld, L. C., Adams, S. L., & Kirsch, T. (2000). Transient chondrogenic phase in the intramembranous pathway during normal skeletal development. Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research, 15(3), 522–533.

    Article  CAS  Google Scholar 

  16. Dimitriou, R., Tsiridis, E., & Giannoudis, P. V. (2005). Current concepts of molecular aspects of bone healing. Injury, 36(12), 1392–1404.

    Article  PubMed  Google Scholar 

  17. Einhorn TA (1998) The cell and molecular biology of fracture healing. Clinical orthopaedics and related research (355 Suppl):S7–21.

  18. Tsiridis, E., Upadhyay, N., & Giannoudis, P. (2007). Molecular aspects of fracture healing: which are the important molecules? Injury, 38(Suppl 1), S11–S25.

    Article  PubMed  Google Scholar 

  19. Phillips, A. M. (2005). Overview of the fracture healing cascade. Injury, 36(Suppl 3), S5–S7.

    Article  PubMed  Google Scholar 

  20. Schindeler, A., McDonald, M. M., Bokko, P., & Little, D. G. (2008). Bone remodeling during fracture repair: the cellular picture. Seminars in Cell & Developmental Biology, 19(5), 459–466.

    Article  CAS  Google Scholar 

  21. Salgado, A. J., Coutinho, O. P., & Reis, R. L. (2004). Bone tissue engineering: state of the art and future trends. Macromolecular Bioscience, 4(8), 743–765.

    Article  CAS  PubMed  Google Scholar 

  22. Kraus, K. H., & Kirker-Head, C. (2006). Mesenchymal stem cells and bone regeneration. Veterinary surgery: VS, 35(3), 232–242.

    Article  PubMed  Google Scholar 

  23. Sacak B, et al. (2016) Repair of critical size defects using bioactive glass seeded with adipose-derived mesenchymal stem cells. Journal of biomedical materials research. Part B, Applied biomaterials. doi:10.1002/jbm.b.33632

  24. Hendrikx, S., et al. (2016). Indirect rapid prototyping of sol-gel hybrid glass scaffolds for bone regeneration - effects of organic crosslinker valence, content and molecular weight on mechanical properties. Acta Biomaterialia, 35, 318–329.

    Article  CAS  PubMed  Google Scholar 

  25. Ren, Z., et al. (2015). Effective bone regeneration using Thermosensitive poly(N-Isopropylacrylamide) grafted gelatin as injectable carrier for bone mesenchymal stem cells. ACS Applied Materials & Interfaces, 7(34), 19006–19015.

    Article  CAS  Google Scholar 

  26. Han LH, et al. (2016) Microribbon-based hydrogels accelerate stem cell-based bone regeneration in a mouse critical-size cranial defect model. Journal of biomedical materials research. Part A, 104(6), 1321–1331.

  27. Levi, B., et al. (2010). Human adipose derived stromal cells heal critical size mouse calvarial defects. PloS One, 5(6), e11177.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Park, J. S., & Park, K. H. (2016). Light enhanced bone regeneration in an athymic nude mouse implanted with mesenchymal stem cells embedded in PLGA microspheres. Biomaterials research, 20, 4.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Nagasaki, R., et al. (2015). A combination of low-intensity pulsed ultrasound and nanohydroxyapatite concordantly enhances osteogenesis of adipose-derived stem cells from Buccal fat pad. Cell medicine, 7(3), 123–131.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Dufrane, D., et al. (2015). Scaffold-free three-dimensional graft from autologous adipose-derived stem cells for large bone defect reconstruction: clinical proof of concept. Medicine, 94(50), e2220.

    Article  CAS  PubMed  Google Scholar 

  31. Rodriguez-Collazo, E. R., & Urso, M. L. (2015). Combined use of the Ilizarov method, concentrated bone marrow aspirate (cBMA), and platelet-rich plasma (PRP) to expedite healing of bimalleolar fractures. Strategies in trauma and limb reconstruction, 10(3), 161–166.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Ajiboye, R. M., Hamamoto, J. T., Eckardt, M. A., & Wang, J. C. (2015). Clinical and radiographic outcomes of concentrated bone marrow aspirate with allograft and demineralized bone matrix for posterolateral and interbody lumbar fusion in elderly patients. European spine journal: official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society, 24(11), 2567–2572.

    Article  Google Scholar 

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Authors and Affiliations

  1. Hagey Laboratory for Pediatric Regenerative Medicine, Department of Surgery, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, 257 Campus Drive Room GK106, Stanford, CA, 94305-5461, USA

    Graham G. Walmsley, Ryan C. Ransom, Elizabeth R. Zielins, Tripp Leavitt, John S. Flacco, Michael S. Hu, Michael T. Longaker & Derrick C. Wan

  2. Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Hagey Building, 257 Campus Dr., Stanford, CA, 94305, USA

    Graham G. Walmsley, Ryan C. Ransom, Michael S. Hu, Andrew S. Lee & Michael T. Longaker

  3. Department of Surgery, John A. Burns School of Medicine, University of Hawai’i, Honolulu, Hawai’i, USA

    Michael S. Hu

Authors
  1. Graham G. Walmsley
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  2. Ryan C. Ransom
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  3. Elizabeth R. Zielins
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  4. Tripp Leavitt
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  5. John S. Flacco
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  6. Michael S. Hu
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  7. Andrew S. Lee
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  8. Michael T. Longaker
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  9. Derrick C. Wan
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Correspondence to Derrick C. Wan.

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Walmsley, G.G., Ransom, R.C., Zielins, E.R. et al. Stem Cells in Bone Regeneration. Stem Cell Rev and Rep 12, 524–529 (2016). https://doi.org/10.1007/s12015-016-9665-5

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  • DOI: https://doi.org/10.1007/s12015-016-9665-5

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