ในตอนเด็ก

ในตอนเด็ก

ผลลัพธ์ (อังกฤษ) 1:

in childhood

ผลลัพธ์ (อังกฤษ) 2:

Childhood

ผลลัพธ์ (อังกฤษ) 3:

DiscussionThe complex causes and mechanisms have led to a numberof hypotheses to explain pathological scars formation, suchas the immunoinflammatory over‑the‑sun holiday hypothesis(i.e. excessive inflammation results in extracellular matrixdeposition and tissue fibrosis), the cytokine regulatory disorderhypothesis, the cell matrix line disorder hypothesis and theepigenetic hypothesis (26,27). However, no single hypothesiscan fully explain the mechanism of pathological scars forma‑tion. Despite that, various hypotheses can hold several viewson the causes of pathological scar formation; excessive fibro‑blast proliferation and deposition of extracellular matrix areconsidered the most significant pathological changes duringthe development of pathological scars (26,27). Therefore,inhibition of fibroblasts proliferation and the suppression ofextracellular matrix synthesis by fibroblasts could be poten‑tial targets for the prevention and treatment of pathologicalscars (28).Previous studies have shown that the transplantation ofmesenchymal stem cells into the large area of wounds canaccelerate wound healing, improve healing quality and reducescar formation (29,30). This suggests that mesenchymal stemcells can inhibit scar formation, which provides an approachfor the treatment of wounds and pathological scars (29,30).Previous studies have shown that mesenchymal stem cellscan inhibit scar hyperplasia through myofibroblasts regula‑tion (31,32), immune response regulation (33), ROS/RNShomeostasis (34) and angiogenesis induction (35). The presentstudy demonstrated that ADSCs inhibited cell proliferationand migration, as well as the protein expression of collagen‑I,collagen‑III, FN and α‑SMA in hypertrophic scar fibroblastsand keloid fibroblasts. Evidently, the present study only inves‑tigated the effect of ADSCs on proliferation, migration and thesynthesis of extracellular matrix in HSFs and KFs in vitro. Thecurrent study was limited to outside the body to circumvent thecomplex environment inside the body, and its conclusion needsto be confirmed in vivo. With the advancements in cell therapyand stem cells understanding, ADSCs are regarded as modelseed cells for cell therapy due to their ability to secrete a largenumber of active factors (36,37) that can act through paracrinemechanisms to exert multiple effects, such as the induction ofwound healing (19), angiogenesis (22), the inhibition of scarformation following myocardial infarction (38) and multi‑direc‑tional differentiation (39). Yoshihiko et al (40) demonstratedthat adipose‑derived stem/stromal cells can inhibit the forma‑tion of vocal cord scars through the regulation of the biologicalbehavior of vocal fold fibroblasts and through the regulationof vocal folds inflammation. Yun et al (41) demonstrated thathuman ADSCs can stimulate scar remodeling in a pig woundmodel by decreasing the activity of mast cells, inhibiting theeffects of TGF‑β on fibroblasts and decreasing the expression ofMMP molecules. In vitro, human ADSCs were shown to inhibitTGF‑β1‑induced differentiation of human dermal fibroblastsand keloid scar‑derived fibroblasts in a paracrine manner (42).The mode of action of ADSCs in the regulation of scarfibroblasts can occur either through direct contact, or throughindirect non‑contact mechanisms (16,17). The present studyestablished an indirect co‑culture system of ADSCs andfibroblasts, including hypertrophic scar fibroblasts and keloidfibroblasts, using a Transwell chamber wherein ADSCs werenot in direct contact with fibroblasts. However, in animalexperiments, ADSCs are in direct contact with scar fibroblasts.While a study has indicated that local injection of adipose stemcells can promote healing and reduce the risk of scar forma‑tion during healing of the injury site (43), ADSCs‑conditionedmedium was alone able to alter the biological behavior of targetcells (44,45). Therefore, the interaction between the two celltypes could be achieved through the influence of receptors, inaddition to their direct interaction.The present study observed that co‑culture with ADSCsinhibited the protein expression of TGF‑β1, p‑Smad2/Smad2,p‑Smad3/Smad3 and Smad7 in HSFs and KFs. The TGF‑βfamily is highly conserved and its members are widelyexpressed during embryonic and tissue development, wherethey have been shown to exhibit different biological functionsin a cell‑dependent and condition‑dependent manner (46).TGF‑β1 is a representative cytokine of the TGF‑β familythat plays an important role in the regulation of the biologicalbehavior of different cell types at different stages of develop‑ment (46). TGF‑β1 exists in complex regulatory networks withdifferent cell signaling pathway molecules that can regulatethe expression of each other (46). In the process of woundhealing, moderate secretion of TGF‑β1 can promo