title: Transplantation of cyclic stretched fibroblasts accelerates the wound-healing process in streptozotocin-induced diabetic mice.
abstract: Mechanical stimulation is a known modulator of survival and proliferation for many cells, including endothelial cells, smooth muscle cells, and bone marrow-derived mesenchymal stem cells. In this study, we found that mechanical strain prevents apoptosis and increases the adhesive ability of dermal fibroblasts in vitro and thus confers the survival advantage in vivo after transplantation of fibroblasts into the full-thickness wound of diabetic mice. Cyclic stretch at a frequency of 0.5 Hz and maximum elongation of 20% stimulates cellular survival mediated by the activation of extracellular signal-regulated kinases (ERKs), c-Jun N-terminal kinases (JNKs), and the serine/threonine kinase Akt (AKT). Stretching of the fibroblasts increases the synthesis of extracellular matrix proteins and the formation of denser focal adhesion structures, both of which are required for fibroblast adhesion. The stretched fibroblasts also upregulate the expression of vascular endothelial growth factor (VEGF) and stromal cell-derived factor-1α (SDF-1α), which enhanced wound healing in vivo. Indeed, preconditioning with mechanical stretch allows better survival of the transplanted fibroblasts, when compared to unstretched control cells, in the wound environment of mice with streptozotocin-induced diabetes and thus accelerates the wound-healing process in these mice.
authors.affiliation: Department of Genetic Engineering, College of Life Science and Graduate School of Biotechnology, Kyung Hee University, Yongin, Korea.
authors.forename: Eunkyung
authors.initials: E
authors.lastname: Lee
authors.forename: Do Yeon
authors.initials: DY
authors.lastname: Kim
authors.forename: Eunkyung
authors.initials: E
authors.lastname: Chung
authors.forename: Eun Ah
authors.initials: EA
authors.lastname: Lee
authors.forename: Ki-Sook
authors.initials: KS
authors.lastname: Park
authors.forename: Youngsook
authors.initials: Y
authors.lastname: Son
mesh_terms: D000818:Animals; D017209:Apoptosis; D001696:Biomechanical Phenomena; D002448:Cell Adhesion; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000628:therapy; D005347:Fibroblasts / Q000166:cytology* / Q000201:enzymology / Q000378:metabolism / Q000637:transplantation*; D006801:Humans; D051379:Mice; D011494:Protein Kinases / Q000378:metabolism; D015398:Signal Transduction; D022502:Stress Fibers / Q000378:metabolism; D013314:Stress, Mechanical; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D014945:Wound Healing
chemical_list: D054377:Chemokine CXCL12; D042461:Vascular Endothelial Growth Factor A; D011494:Protein Kinases