Optimal Administration Routes for Adipose-Derived Stem Cell Therapy in Ischemic Flaps

Abstract

Improvement of flap survival represents an ongoing challenge in reconstructive surgery. The angiogenic potential of adipose-derived stem cells (ASCs) offers a promising approach to improve viability of random pattern flaps. Recently, to maximize the therapeutic effects of ASCs, increasing focus is being placed on how to deliver the stem cells to target lesions. The purpose of the present study was to compare the effectiveness of different administration routes of ASCs to improve the viability of the random pattern skin flap. ASCs labeled with PKH26 were applied via four methods to the cranially-based random pattern skin flaps of rats: 1) intravenous injection; 2) subcutaneous injection; 3) application with collagen sponge seeding; and 4) application with fibrin glue seeding. ASCs led to a significant increase in flap viability in the subcutaneous injection group and the collagen sponge group. Cutaneous blood flow was increased in the intravenous injection, subcutaneous injection, and collagen sponge groups. Capillary density in the intravenous injection group and collagen sponge group was significantly greater than in the control group (no treatment). PKH26-positive cells via the collagen sponge were distributed more densely within the flap than in other groups. This study demonstrated that the collagen sponge method delivered ASCs most effectively within the flap and increased flap vascularity. The clinical therapeutic effects of ASCs can therefore be maximized when the optimal delivery route is chosen.