Effects of Administration Route of Adipose-Derived Stem Cells on the Survival of Allogeneic Skin Grafts in Mice

Abstract

Composite tissue allotransplantation presents considerable potential for defective tissue reconstruction. However, the high immunogenicity of the allogeneic skin grafts can cause acute rejection. Adipose-derived stem cells (ADSCs) reportedly have an immunomodulation potential, which may improve the survival of allogeneic skin grafts. However, there is currently no consensus on administration route of ADSCs. This study compared the effectiveness of local injection vs intravenous (IV) administration of ADSCs in improving the survival of allogenic skin grafts in mice. BALB/c and C57BL/6 mice were used as skin graft donors and recipients, respectively. Mice were divided into 3 groups for IV injection of ADSCs (IV group) or phosphate-buffered saline (PBS; control), or for local injection in the fascial layer of the recipient bed (FL group). After allogeneic skin transplantation, 0.1 mL of PBS alone or with 1.5×105 ADSCs was immediately injected. The grafts were histologically evaluated on days 7 and 14 postoperation. The graft necrotic area was significantly smaller in the IV and FL groups than in the control group. Additionally, the grafts in these 2 groups exhibited decreased interleukin 17/6, tumor necrosis factor-α, and interferon-γ messenger mRNA levels; inflammatory changes; and cluster of differentiation 4 expression, and increased expression of vascular endothelial growth factor expression (P < .05). However, these 2 groups did not significantly differ (P > .05). ADSCs increased the survival of allogeneic skin grafts in mice regardless of IV or FL route of administration, and this effect is likely through anti-inflammatory and angiogenic effects of ADSCs.