Lovvorn H N, Cass D L, Sylvester K G, Yang E Y, Crombleholme T M, Adzick N S, Savani R C
The Children's Institute for Surgical Science, The Children's Hospital of Philadelphia, The University of Pennsylvania School of Medicine, 19104, USA.
J Pediatr Surg. 1998 Jul;33(7):1062-9; discussion 1069-70. doi: 10.1016/s0022-3468(98)90532-2.
BACKGROUND/PURPOSE: The midgestation fetus heals incisional skin wounds scarlessly, whereas large excisional wounds scar. High concentrations of hyaluronan (HA) are associated with scarless fetal as opposed to scar-forming adult wound repair. Because expression of the HA receptors, CD44 and RHAMM (Receptor for HA-Mediated Motility), has been associated with adult wound fibroplasia, the authors postulated that fetal excisional wounds would show increased expression of CD44 and RHAMM as compared with incisional wounds.
Two models of fetal wound healing were examined. Fetal skin from human abortuses was heterotransplanted subcutaneously into severe combined immunodeficient (SCID) mice. Fourteen days after grafting, incisional or 2-mm excisional wounds were created (n = 6 per time-point). In addition, incisional and excisional (6 to 10 mm) wounds (n = 5 per time-point) were created on the backs of 70- to 75-day fetal lambs (term, 145 days). Tissue from both models was harvested at sequential time-points after injury. Wounds were studied histologically for fibroplasia and assayed for their HA content. CD44 and RHAMM expression were analyzed by immunohistochemistry and immunoblotting.
As expected, in both models, incisional wounds healed scarlessly, whereas excisional wounds showed fibroplasia. Incisional wounds of fetal lambs maintained a significantly higher HA content than excisional wounds 3 days after injury. Between 1 and 7 days in either human or sheep fetal wounds, immunostaining for CD44 and RHAMM markedly increased along the margins of excisional wounds as compared with incisional wounds and unwounded skin. Immunoblot analysis confirmed this increased HA receptor expression in both models.
HA receptor expression increased in both human and sheep fetal excisional wounds and correlated with fibroplasia and a reduced HA content. The authors speculate that strategies to limit the expression or function of HA receptors during postnatal wound repair may modify the development of scar.
背景/目的：妊娠中期胎儿的皮肤切口伤口可无痕愈合，而大面积切除伤口则会形成瘢痕。与形成瘢痕的成人伤口修复相反，高浓度的透明质酸（HA）与胎儿无痕伤口修复相关。由于HA受体CD44和RHAMM（HA介导的运动受体）的表达与成人伤口纤维增生有关，作者推测与切口伤口相比，胎儿切除伤口会显示出CD44和RHAMM表达增加。
研究了两种胎儿伤口愈合模型。将人工流产胎儿的皮肤异体皮下移植到严重联合免疫缺陷（SCID）小鼠体内。移植14天后，造成切口或2毫米切除伤口（每个时间点n = 6）。此外，在70至75日龄的胎羊（足月为145天）背部造成切口和切除（6至10毫米）伤口（每个时间点n = 5）。在损伤后的连续时间点收集两个模型的组织。对伤口进行组织学检查以观察纤维增生情况，并检测其HA含量。通过免疫组织化学和免疫印迹分析CD44和RHAMM的表达。
如预期的那样，在两个模型中，切口伤口均无痕愈合，而切除伤口则显示出纤维增生。胎羊的切口伤口在损伤后3天的HA含量明显高于切除伤口。在人类或绵羊胎儿伤口的1至7天内，与切口伤口和未受伤皮肤相比，切除伤口边缘的CD44和RHAMM免疫染色明显增加。免疫印迹分析证实了两个模型中HA受体表达的增加。
人类和绵羊胎儿切除伤口中的HA受体表达均增加，且与纤维增生和HA含量降低相关。作者推测，在出生后伤口修复过程中限制HA受体表达或功能的策略可能会改变瘢痕的形成。
