Skin and soft tissue expansion stimulates the proliferation of skin epidermal basal cells and increase the dermal collagen deposition and angiogenesis. To explore the contribution of bone marrow-derived stem cells (BMSCs) to the generation of `` new'' skin during the expansion, we used a chimeric mouse model in which the donor C57BL mice were engrafted with the bone marrow of enhanced green fluorescent protein (EGFP) transgenic mice. BMSCs were collected from the tibia and femur of EGFP_ transgenic mice, and then injected into normal C57BL mice via the tail vein (chimeric mice). The chimeric mice were randomized into groups A, B, and C. Silicone expanders were implanted in the backs of the Group Amice and then were injected with normal saline (N. S.); silicone expanders were also implanted in the backs of the Group B mice but the expanders were not injected with N. S.; and no expanders were implanted in the Group C mice. Skin was obtained at different times (days 0, 7, 14, 21, 28, and 35). Skin stromal-derived factor-1 (SDF-1) expression was evaluated. The number, distribution, and phenotype changes of EGFP(+) cells in the skin were also evaluated by means of fluorescent microscopy. EGFP_ cells were present stably in the normal skin. The number of EGFP(+) cells of the Group A mice changed with the tension, and reached the peak on day 21(17.1 +/- 6.7%), as compared with either Group B (5.5 +/- 1.0%) or Group C (5.1 +/- 0.9%). The SDF-1 expression in the expanded skin was significant increased (approximate to 11-fold, P < 0.01) compared to non-expanded skin on day 21. Immunofluorescence showed EGFP(+) cells were converted into vascular endothelial cells, epidermal cells, and spindle-shaped dermal fibroblasts. Strain can promote the expression of SDF-1 and facilitate the differentiation and proliferation of BMSCs in the expanded skin. J. Cell. Physiol. 226: 2834-2840, 2011. (C) 2011 Wiley-Liss, Inc.