Optimizing adipose-derived stem cell therapy for diabetic foot ulcers

Figure 6 Effects of adipose-derived mesenchymal stem cells on tissue regeneration. A: Masson’s trichrome staining showed increased collagen deposition in the dermis of mice on day 7 after subcutaneous adipose-derived mesenchymal stem cell (ADSC) injection, with the most significant effect observed in the medium-dose group, n = 7; B and C: Immunohistochemical staining of collagen I and Ki67 in the wound beds of diabetic foot ulcers model mice on day 7 after subcutaneous ADSC administration, n = 5; D: Exposure to advanced glycation end products (AGE) inhibited human dermal fibroblast (HDF) proliferation, and ADSCs reversed this inhibitory effect; E and F: AGE inhibited HDF migration, and ADSCs reversed this inhibitory effect; G and H: Reverse transcription-quantitative polymerase chain reaction and western blot analysis demonstrated that in an AGE environment, HDFs overexpressed key genes of the Notch signaling pathway, namely Notch1, Jagged1, and Notch intracellular domain, as well as matrix metalloproteinase-2 and matrix metalloproteinase-9, while collagen I and III were downregulated. However, coculture with ADSCs inhibited Notch1, Jagged1, Notch intracellular domain, matrix metalloproteinase-2, and matrix metalloproteinase-9 expression and restored collagen I and III expression. The data are presented as mean ± SD. Scale bar, 100 μm. HDFs: Human dermal fibroblasts; AGE: Advanced glycation end products; ADSCs: Adipose-derived mesenchymal stem cell; OD: Optical density; NICD: Notch intracellular domain; MMP2: Matrix metalloproteinase-2; MMP9: Matrix metalloproteinase-9; GAPDH: Glyceraldehyde 3-phosphate dehydrogenase. ^aP < 0.05 vs control, ^bP < 0.05 vs model, ^cP < 0.01 vs model, ^dP < 0.05 vs human dermal fibroblasts, ^eP < 0.01 vs human dermal fibroblasts, ^fP < 0.001 vs human dermal fibroblasts, ^gP < 0.0001 vs human dermal fibroblasts, ^hP < 0.01 advanced glycation end products-human dermal fibroblasts, ⁱP < 0.001 advanced glycation end products-human dermal fibroblasts, and ^jP < 0.0001 vs advanced glycation end products-human dermal fibroblasts.