Healing of Full-Thickness Wounds Using Platelet-Rich Fibrin Seeded with Adipose Stem Cells in a Diabetic Mouse Model

Abstract

Diabetic wounds are refractory to spontaneous healing and treatment regimes due to their detrimental nature. Adipose derived stem cells (ASCs) hold great potential in stem cell-based therapies. However, insufficient cell activity and survival after transplantation dramatically reduce the therapeutic effects. Platelet-rich fibrin (PRF) is a great source of growth factors and has been widely used in clinical practice, but few studies explored its application in diabetic wounds. This study was designed to investigate therapeutic effect of PRF as a delivery scaffold of ASCs on promoting healing of diabetic wound in a mouse model. ASCs isolated from subcutaneous fat were cultured in the three-dimensional PRF scaffold for 3 and 7 days, respectively. H&E staining, laser scanning confocal microscopy (LSCM) and scanning electron microscopy (SEM) observation revealed that ASCs could survive and proliferate in PRF. Cell numbers in PRF increased dramatically in the duration of 7 days post-seeding. Meanwhile, it is revealed that conditioned medium of PRF enhanced ASCs proliferation and migration in an in vitro wound model. Furthermore, transplantation of PRF alone or PRF loaded with ASCs improved significantly diabetic wound repair, respectively. Capillary density in wounds received either PRF or PRF-ASCs was significantly higher than wounds without intervention. A in vivo survival assay was also conducted to find that PRF could maintain ASCs cells survive in diabetic wounds. Our study indicated that PRF, in particular that loaded with ASCs, can be considered as a promising approach in the treatment of diabetic wounds.