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Stromal cells and stem cells in clinical bone regeneration

Key Points

  • Stromal cells and/or stem cells can be isolated from different tissues on the basis of plastic adherence and surface-antigen profiles, thereby providing opportunities for bone regeneration

  • The regenerative potential of therapies that are based on adipose-tissue-derived and bone-marrow-derived mesenchymal stromal or stem cells is being tested clinically for the treatment of craniofacial bone defects, tibial non-unions and osteonecrosis of the femoral head

  • Although most approaches in this area use autologous cells, allogeneic sources that include commercially available allograft cell-based products are being investigated

  • Widespread use of cell-based products requires the development and standardization of guidelines and protocols for the shipment and storage of cell therapeutics

  • Despite strong clinical data, which indicates enhanced regenerative outcomes following stromal-cell or stem-cell transplantation, further insight is needed into the mechanisms of action of these strategies

  • Opportunities exist to develop technologies that improve cell survival, morphogenesis and functionality to advance cell therapy as standard care for the treatment of bone defects

Abstract

Stem-cell-mediated bone repair has been used in clinical trials for the regeneration of large craniomaxillofacial defects, to slow the process of bone degeneration in patients with osteonecrosis of the femoral head and for prophylactic treatment of distal tibial fractures. Successful regenerative outcomes in these investigations have provided a solid foundation for wider use of stromal cells in skeletal repair therapy. However, employing stromal cells to facilitate or enhance bone repair is far from being adopted into clinical practice. Scientific, technical, practical and regulatory obstacles prevent the widespread therapeutic use of stromal cells. Ironically, one of the major challenges lies in the limited understanding of the mechanisms via which transplanted cells mediate regeneration. Animal models have been used to provide insight, but these models largely fail to reproduce the nuances of human diseases and bone defects. Consequently, the development of targeted approaches to optimize cell-mediated outcomes is difficult. In this Review, we highlight the successes and challenges reported in several clinical trials that involved the use of bone-marrow-derived mesenchymal or adipose-tissue-derived stromal cells. We identify several obstacles blocking the mainstream use of stromal cells to enhance skeletal repair and highlight technological innovations or areas in which novel techniques might be particularly fruitful in continuing to advance the field of skeletal regenerative medicine.

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Figure 1: Generalized clinical approach for stem-cell-based regeneration of large craniofacial bone defects.

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Acknowledgements

The authors acknowledge funding from the Maryland Stem Cell Research Fund (2014-MSCRFI-0699), NSF CAREER award (CBET 1350554), Johns Hopkins University Centre for Musculoskeletal Research, and the American Society for Bone and Mineral Research (2013CEA13). The authors also thank D. Hutton for assistance with the artwork.

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W.L.G., B.P.H. and J.M.G. researched data for the article and wrote the article. W.L.G., B.A.B., E.M., T.F. and J.M.G. made substantial contributions to discussions of the content. All authors reviewed and/or edited the manuscript before submission.

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Correspondence to Warren L. Grayson.

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J.M.G. is co-founder, co-owner and Chief Scientific Officer of LaCell, a biotechnology company focusing on the clinical translation of stromal-cell and stem-cell science. The other authors declare no competing interests.

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Grayson, W., Bunnell, B., Martin, E. et al. Stromal cells and stem cells in clinical bone regeneration. Nat Rev Endocrinol 11, 140–150 (2015). https://doi.org/10.1038/nrendo.2014.234

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