Peripheral blood-derived multipotent mesenchymal stromal cells circulate in low number. They share, most although not all, of the surface markers with bone marrow-derived multipotent mesenchymal stromal cells, possess diverse and complicated gene expression characteristics, and are capable of differentiating along and even beyond mesenchymal lineages. Although their origin and physio-pathological function are still unclear, their presence in the adult peripheral blood might relate to some interesting but controversial subjects in the field of adult stem cell biology, such as systemic migration of bone marrow-derived multipotent mesenchymal stromal cells and the existence of common hematopoietic-mesenchymal precursors. In this review, current studies/knowledge about peripheral blood-derived multipotent mesenchymal stromal cells is summarized, and the above-mentioned topics are discussed. STEM CELLS 2007;25:69 -77
Mesenchymal stem cells (MSCs) were demonstrated to exist within peripheral blood (PB) of several mammalian species including human, guinea pig, mice, rat, and rabbit. Whether or not the PB derived MSCs (PBMSCs) could enhance the regeneration of large bone defects have not been reported. In this study, rabbit MSCs were obtained from mononuclear cells (MNCs) cultures of both the PB and bone marrow (BM) origin. The number of PBMSCs was relatively lower, with the colony forming efficiency (CFE) ranging from 1.2 to 13 per million MNCs. Under specific inductive conditions, PBMSCs differentiated into osteoblasts, chondrocytes, and adipocytes, showing multidifferentiation ability similar to BMMSCs. Bilateral 20 mm critical-sized bone defects were created in the ulnae of 12 6-month-old New Zealand white rabbits. The defects were treated with allogenic PBMSCs/Skelite (porous calcium phosphate resorbable substitute), BMMSCs/Skelite, PBMNCs/ Skelite, Skelite alone, and left empty for 12 weeks. Bone regeneration was evaluated by serial radiography, peripheral quantitative computed tomography (pQCT), and histological examinations. The X-ray scores and the pQCT total bone mineral density in the PBMSCs/Skelite and BMMSCs/ Skelite treated groups were significantly greater than those of the PBMNCs/Skelite and Skelite alone groups ( p < 0.05), respectively. Histologically, newly formed bone was evident in the PBMSCs/ Skelite and BMMSCs/Skelite treated groups. The findings demonstrated that the rabbit PBMSCs possessed multidifferentiation potential comparable with BMMSCs, allogenic PBMSCs seeded onto porous calcium phosphate resorbable substitutes enhanced bone regeneration in the rabbit ulna critical-sized bone defect model, suggesting allogenic PBMSCs may be a new source of circulating osteogenic stem cells for bone regeneration and tissue engineering. ß
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