EXPERIMENTAL STUDY An emerging cell-based strategy in orthopaedics: endothelial progenitor cells Kivanc Atesok • Tomoyuki Matsumoto • Jon Karlsson • Takayuki Asahara • Anthony Atala • M. Nedim Doral • Rene Verdonk • Ru Li • Emil Schemitsch Received: 30 November 2011 / Accepted: 15 December 2011 / Published online: 9 March 2012 Ó Springer-Verlag 2012 Abstract Purpose The purpose of this article was to analyze the results of studies in the literature, which evaluated the use of endothelial progenitor cells (EPCs) as a cell-based tissue engineering strategy. Methods EPCs have been successfully used in regenera- tive medicine to augment neovascularization in patients after myocardial infarction and limb ischemia. EPCs’ important role as vasculogenic progenitors presents them as a potential source for cell-based therapies to promote bone healing. Results EPCs have been shown to have prominent effects in promoting bone regeneration in several animal models. Evidence indicates that EPCs promote bone regeneration by stimulating both angiogenesis and osteogenesis through a differentiation process toward endothelial cell lineage and formation of osteoblasts. Moreover, EPCs increase vascularization and osteogenesis by increased secretion of growth factors and cytokines through paracrine mechanisms. Conclusion EPCs offer the potential to emerge as a new strategy among other cell-based therapies to promote bone regeneration. Further investigations and human trials are required to address current questions with regard to biology and mechanisms of action of EPCs in bone tissue engineering. Keywords Endothelial progenitor cell (EPC) Á Bone tissue engineering Á Cell-based therapy Á Fracture healing K. Atesok (&) Á R. Li Á E. Schemitsch (&) Musculoskeletal Research Laboratory, Division of Orthopaedic Surgery, St. Michael’s Hospital, University of Toronto, 55 Queen St. E., Suite 800, Toronto, ON M5C 1R6, Canada e-mail: Kivanc.Atesok@utoronto.ca E. Schemitsch e-mail: SchemitschE@smh.ca T. Matsumoto Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Chuo-ku, Kobe 650-0017, Japan J. Karlsson Department of Orthopaedics, Sahlgrenska University Hospital, Sahlgrenska Academy at Gothenburg University, Molndal 431 80, Sweden T. Asahara Regenerative Medicine Science, Tokai University School of Medicine, Kanagawa, Isehara 259-1193, Japan T. Asahara Vascular Regeneration Research Group, Institute of Biomedical Research and Innovation, Kobe, Hyogo 650-0047, Japan A. Atala Wake Forest Institute for Regenerative Medicine, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA M. N. Doral Department of Orthopaedics and Traumatology & Department of Sports Medicine, Hacettepe University, Sihhiye, 06100 Ankara, Turkey R. Verdonk Department of Orthopaedic Surgery and Traumatology, Gent State University Hospital, De Pintelaan 185, 9000 Gent, Belgium 123 Knee Surg Sports Traumatol Arthrosc (2012) 20:1366–1377 DOI 10.1007/s00167-012-1940-7