Inadequate blood supply frequently impedes the viability of tissue-engineered constructs in the
initial phase after implantation, and can lead to improper cell integration or cell death. Vascularization
using stem cells has continued to evolve as a potential solution to this problem. In this review, we summarize
studies that utilize endothelial progenitor cells (EPCs) for musculoskeletal regeneration. This review
will also highlight recent concepts for EPC identification in conjunction with the development of
EPC biology research. EPCs promote bone regeneration in animal models through a variety of mechanisms.
By differentiating toward endothelial cell lineages and osteoblasts, EPCs stimulate vasculogenesis,
angiogenesis and osteogenesis. Moreover, EPCs influence supporting cells through the secretion of
growth factors and cytokines. Phase I/II clinical trials have applied circulating CD34+ cells/EPCs to nonunion
bone fractures and have exhibited promising results including accelerated bone healing. Similar
mechanisms of angiogenesis and osteogenesis are proposed for anterior cruciate ligament (ACL) ruptured
tissue derived CD34+ cells, and thus EPCs have implied a critical role at the site of tendon-bone integration.
EPCs are an emerging strategy among other cell-based therapies in the field of orthopaedics for the
promotion of musculoskeletal regeneration.
Keywords: Bone tissue engineering, cell-based therapy, endothelial progenitor cell (EPC), fracture healing, musculoskeletal
injury, tendon regeneration.
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