小抹香鯨科全層皮膚傷口癒合之組織病理學研究及其對再生醫學的影響

Abstract

皮膚傷口癒合是一個複雜的過程，包括止血、炎症、增生、重塑和傷疤形成等不同階段。本研究調查了深潛海洋哺乳動物的全層皮膚傷口癒合過程，重點研究了小抹香鯨科，包括侏儒抹香鯨和小抹香鯨。研究發現，小抹香鯨科展現出獨特的傷口癒合機制，在增生和重塑階段的傷口中產生大量的III型膠原蛋白（Col III），表明它們具有類似於鹿角、蠑螈和人類胎兒的無疤傷口癒合過程。在重塑階段，小抹香鯨科的細胞外基質呈現不規則的膠原蛋白結構，與人類和弗氏海豚中規則排列的疤痕組織形成鮮明對比。免疫螢光染色顯示，在重塑階段，小抹香鯨科的傷口組織呈現近似人類傷疤的CD34-/α-SMA+/Ki67-表型，這與其不規則的膠原蛋白結構相衝突，表明小抹香鯨科的重塑階段與典型疤痕的形成不同。此外，染色結果還暗示了休止狀態的纖維母細胞及肌纖維母細胞的存在，這可能促成了小抹香鯨科的無疤癒合。小抹香鯨科在增生階段即開始脂肪細胞的重新生成，而弗氏海豚則要到重塑階段才開始。小抹香鯨科較早的脂肪細胞生成可能由血管生成和脂肪前驅細胞的分化所驅動。本研究顯示，小抹香鯨科與弗氏海豚在皮膚傷口癒合過程中存在顯著差異，這可能是由於小抹香鯨科的深潛行為和環境適應所致。結果表明，大量的Col III生成和早期脂肪細胞生成可能促進小抹香鯨科在高壓和低溫環境下快速恢復受損皮膚。本研究為深潛鯨類的傷口癒合機制提供了寶貴的見解，並為獸醫和人類再生醫學提供了潛在的應用。進一步研究這些獨特的過程可能發展出新的組織修復策略。

Cutaneous wound healing is a complex process comprising several distinct stages: hemostasis, inflammation, proliferation, remodeling, and scar formation. This study investigates the full-thickness skin wound healing process in deep-diving marine mammals, focusing on the Kogia species, which includes pygmy and dwarf sperm whales. This research reveals that Kogia species exhibit a unique wound healing mechanism characterized by a unique ratio of type III collagen (Col III) to type I collagen (Col I). Unlike the well-known process in humans, Kogia species exhibit an extremely high ratio of Col III to Col I throughout the proliferation and remodeling stages, suggesting a capability for scarless wound healing similar to that observed in deer antlers, salamanders, and human fetuses. During the remodeling stage, the extracellular matrix of Kogia species shows a disorganized collagen structure, in contrast to the organized scar tissue seen in humans and Fraser’s dolphins. Immunofluorescence staining revealed that during the remodeling stage, the wound tissue in Kogia species exhibited a CD34-/α-SMA+/Ki67- pattern, similar to that of human scars. This finding contrasts with the disorganized collagen structure observed in Kogia species, suggesting that the remodeling stage in Kogia differs from typical scar formation. This pattern suggests the presence of quiescent fibroblasts and myofibroblasts, which may contribute to the observed scarless healing. Additionally, Kogia species demonstrate early adipocyte restoration during the proliferation stage, a trait not seen in Fraser’s dolphins until the remodeling stage. This early adipocyte recovery is potentially driven by angiogenesis and the differentiation of adipose progenitor cells. The findings in this study highlight significant differences in the skin wound healing processes between Kogia species and Fraser’s dolphins, likely influenced by their deep-diving behavior and environmental adaptations. These results suggest that the high ratio of Col III to Col I and the early adipocyte restoration play crucial roles in facilitating rapid skin integrity restoration in high-pressure and low-temperature environments. This study provides valuable insights into the wound healing mechanisms of deep-diving cetaceans, offering potential applications for regenerative medicine in both veterinary and human contexts. Further research into these unique processes could lead to innovative strategies for enhancing tissue repair and regeneration.