Adipose-derived mesenchymal stem cells treatments for fibroblasts of fibrotic scar via downregulating TGF-β1 and Notch-1 expression enhanced by photobiomodulation therapy

Excerpt

Wounds of skin often heal with scar formation. Generally, adverse scar (keloid or hypertrophic scar) formation is characterized with negative cosmetic and psychological effects. Various therapeutic approaches have been studied for keloid and hypertrophic scar, which include occlusive dressings, local injection, surgical excision, etc. [1‐6]. Some identified genetic, systemic, and local factors make contributions to the pathogenesis of keloid and hypertrophic scar [7‐10]. And local mechanical forces also play a significant role in the formation of adverse scar [11, 12]. Previous studies demonstrate that epithelial-mesenchymal transition (EMT) and myofibroblast transition plays an important role in aberrant scar formation, which can be induced by a regulatory network formed by multiple signaling pathways, especially transforming growth factor beta 1 (TGF-β1) as a critical driver [13‐16]. Similarly, TGF-β1-induced EMT can also be meditated by other signaling pathways through direct interactions or transcription [17‐19]. Notch signaling, an evolutionarily conserved pathway that regulates multiple cellular process, was proved to play a key role in regulating fibroblast activation and EMT [20, 21]. And interestingly, a great body of evidence supports that TGF-β and Notch signaling regulate EMT and fibrogenesis cooperatively [22‐24]. However, understanding into the keloid and hypertrophic scar pathogenesis is still lacking, which contributes to less proper treatment strategies. As lately studies show that formation of these abnormal scars share several pathological processes with other fibrotic diseases, and may occur as a result of fibroproliferative disorder [10, 25]. And increasing evidence indicates that mesenchymal stem cells (MSCs) has been a potential treatment for fibroproliferative disorder by recruitment of macrophage and T cell, upregulation of vascular endothelial growth factors and initiation of angiogenesis, secretion of anti-fibrotic factors, promotion of dermal fibroblast functions, and differentiation into cutaneous cell types [26‐29]. …