Reversible Adipose Tissue Enlargement Induced by External Tissue Suspension: Possible Contribution of Basic Fibroblast Growth Factor in the Preservation of Enlarged Tissue

Abstract

Various kinds of tissue expansion have been performed clinically with internal devices, but external expansion has not been previously investigated. We applied continuous external force on skin tissue in a mouse model. Four weeks of external suspension caused enlargement of the subcutaneous tissue, particularly adipose tissue, although the enlargement was reversible. We found that the enlarged tissue volume could be adequately sustained with controlled release of basic fibroblast growth factor (bFGF), administered at the time the device was removed. Ki67+ proliferating cells, perilipin+ small adipocytes, lectin+ capillaries, and glycerol-3-phosphate dehydrogenase activity in the tissue increased during the expansion process, indicating dynamic adipose remodeling with adipogenesis and angiogenesis. Histological analyses revealed that vessels had elongated in the direction of the external force. Adipose-resident progenitor cells (adipose-derived stem/stromal cells) were the primary proliferating cell population involved in the remodeling process, particularly in the superficial layer. Treatment with bFGF did not enhance the small adipocyte number, but promoted angiogenesis; this mechanism may contribute to the preservation of enlarged tissue. Our results suggested that external tissue suspension induced adipose tissue enlargement by activating resident progenitor cells and that this external suspension approach, combined with controlled release of bFGF, has therapeutic potential for soft tissue engineering.