牙龈间充质干细胞修复创伤性口腔溃疡

Gingiva-derived mesenchymal stem cells in repair of traumatic oral ulcer

背景:牙龈间充质干细胞具有促进皮肤组织损伤愈合的作用,但其对口腔溃疡是否具有潜在的治疗作用尚未见明确报道。目的:探讨牙龈间充质干细胞在创伤性口腔溃疡愈合中的治疗潜力。方法:21只SD大鼠采用机械联合化学法建立大鼠口腔溃疡动物模型,随机分为2组:溃疡组和牙龈间充质干细胞组,溃疡组11只,牙龈间充质干细胞组10只,牙龈间充质干细胞组于造模第2天在溃疡中心及周围局部注射牙龈间充质干细胞悬液,每只大鼠注射细胞总量为1×10^(6)个,溃疡组注射等量PBS,溃疡组造模后1d取1只大鼠验证溃疡造模是否成功,其余溃疡组及牙龈间充质干细胞组大鼠于造模后3,7 d采用大体观察和组织学方法观察溃疡愈合情况,每组每个时间点5只大鼠。结果与结论:①体外培养的牙龈间充质干细胞呈梭形、纺锤样结构,似成纤维细胞,胞体饱满,具有成骨成脂分化潜能;②采用机械联合化学法可成功进行口腔溃疡造模,溃疡组自然愈合过程中可见第3天溃疡炎症反应最重,第7天可见溃疡面积缩小呈现愈合趋势,但大体观察仍然可见溃疡创面,尚未完全愈合;③造模后第3天,大体观察溃疡组的炎症反应强于牙龈间充质干细胞组,造模后第7天牙龈间充质干细胞组溃疡创面已基本愈合;④造模后第7天,苏木精-伊红染色可见牙龈间充质干细胞组溃疡处可见薄层上皮形成;Masson染色可见牙龈间充质干细胞组胶原形成较溃疡组粗大,且排列更加规则;⑤结果表明,牙龈间充质干细胞在大鼠创伤性口腔溃疡早期具有降低炎症反应的作用,对于口腔溃疡的愈合具有促进作用,其口腔上皮的形成时间更早,且胶原形成较粗大,排列更加规则。

BACKGROUND:Gingiva-derived mesenchymal stem cells can promote the wound healing of skin tissue.However,it has not been clearly reported whether it has a potential therapeutic effect on oral ulcers.OBJECTIVE:To study the therapeutic potential of gingiva-derived mesenchymal stem cells in traumatic oral ulcer.METHODS:The animal models of oral ulcer in 21 SD rats were established by mechanical combined with chemical method.They were randomly divided into two groups:ulcer group containing 11 rat,and gingiva-derived mesenchymal stem cell group containing 10 rats.A total of 1×10^(6) gingiva-derived mesenchymal stem cells were injected at ulcer center and surrounding area in every rat of gingiva-derived mesenchymal stem cell group at 2 days after model establishment.The rats in ulcer group were injected with the same amount of PBS.Only one rat in ulcer group was executed one day after modeling to observe the formation of ulcer.The other rats were executed 3 and 7 days after modeling,5 rats in each group at different time points.Ulcer healing was observed by gross observation and histology.RESULTS AND CONCLUSION:(1)Gingiva-derived mesenchymal stem cells cultured in vitro showed spindle-like structure,similar to fibroblasts,presenting full cell body with osteogenic and adipogenic differentiation potential.(2)The model of oral ulcer could be successfully established by mechanical combined with chemical method.During natural healing of ulcer group,the inflammatory reaction of the ulcer reached its most severe on day 3.On day 7,the ulcer showed a healing trend,but had not achieved completely healing.(3)On day 3 after modeling,the inflammatory response of the ulcer group was stronger than that of the gingiva-derived mesenchymal stem cell group.On day 7,the ulcer wound in the gingiva-derived mesenchymal stem cell group had achieved basically healing.(4)The hematoxylin-eosin staining showed the formation of thin epithelium at the ulcer in the gingiva-derived mesenchymal stem cell group on day 7.Masson staining results showed that the collagen formation in the gingiva-derived mesenchymal stem cell group was thicker and more regular than that in the ulcer group on day 7 after modeling.(5)These results suggest that gingiva-derived mesenchymal stem cells can reduce the inflammatory response in the early stage of traumatic oral ulcer in rats and promote the healing process of oral ulcer.The formation time of the oral epithelium is earlier,and the collagen formation is thicker and the arrangement is more regular.