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Cell-based tissue engineering concepts are becoming an important therapeutic alternative in the treatment of traumatic or chronic skeletal diseases. Here, we have evaluated cord blood-derived unrestricted somatic stem cells (USSCs) for use in bone and cartilage repair strategies.This type of somatic stem cell can be generated from cord blood with a current rate of 29% and we have documented excellent proliferation potential to high passage numbers. The cells have an initial population doubling time of 39 h, which slightly decreased with increasing passage number, but cells maintained their proliferation abilities up to passage 23. Cells clearly differentiated towards chondrogenic, adipogenic and osteogenic lineage as shown by reverse transcription-polymerase chain reaction as well as by histological, biochemical and immunohistochemical stains. Differentiation potential of USSCs was observed at passage 6, passage 15 and passage 21. In addition, USSCs showed increased secretion of vascular endothelial growth factor (VEGF) during osteogenic differentiation, as well as expression of key markers of angiogenesis such as vascular endothelial growth factor receptor-2 and platelet/endothelial cell adhesion molecule.USSCs when transplanted into a bone defect might support the repair process not only by pure remineralization but also by installation of angiogenic environment.