FETAL WOUND HEALING

胎儿伤口愈合

• 批准号: 3326650
• 负责人: MICHAEL R HARRISON
• 金额: $ 21.14万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-12-01 至 1992-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3326650
• 关键词: amniotic fluid; carbohydrate metabolism; electron microscopy; embryo /fetus; extracellular matrix; fluorescent dye /probe; gel electrophoresis; gestational age; homologous transplantation; hyaluronate; immunocytochemistry; inflammation; keloid skin disorder; mature animal; microscopy; model design /development; radioimmunoassay; scars; sheep; skin; urinalysis; wound healing

The fetus responds to injury in a fashion fundamentally different from the adult: the process of mesenchymal regeneration proceeds in the absence of inflammation and scarring. We postulate that differences in the extracellular matrix, specifically the early appearance and prolonged maintenance of an environment rich in hyaluronic acid (HA), facilitates cell mobility, cell proliferation, and regeneration in fetal wounds. We propose to characterize the process of healing linear and open wounds in adult sheep and fetal lambs at various gestational ages. The fetal lamb is large enough to compare 1 cm linear incisions, 9 mm open wounds, and adjacent unwounded tissue, and to document the sequential appearance and disappearance of the cellular and extracellular components of repair using the following techniques: a) light microscopy including special stains, b) immunolocalization using fluorescent antibodies to identify cell markers and extracellular matrix components, c) electron microscopy, and d) localization of hyaluronic acid using a newly developed HA-binding protein stain. This model allows us to determine the effect of gestational age by comparing the healing process in adults and fetuses at 60, 100, and 130 days' gestation (term = 145 days). The fetal lamb model can be surgically manipulated to elucidate the effect of the fetal environment on healing: we will compare the process of healing skin and visceral wounds exposed to amniotic fluid to those excluded from amniotic fluid. We will also compare wounds made in adult (maternal) skin allografted onto the fetus at 60 days' gestation (the fetus is tolerant of skin grafts until 70 days) to wounds made on adjacent autografted fetal skin. Recent evidence suggests that prolonged maintenance of HA is central to fetal wound healing. We will compare HA deposition and metabolism in adult wounds and fetal wounds at various gestational ages. After documenting the morphology of HA deposition in our model, we will examine the biochemistry of HA deposition and metabolism by analyzing wound fluid (aspirated from wire mesh cylinders) as well as serum, urine and amniotic fluid using newly developed assays for HA synthesis, hyaluronidase activity, hyaluronidase inhibitors, and newly discovered HA stimulating and inhibiting factors. The devastating clinical problems associated with inflammation and scar formation may be alleviated by modulating the extracellular matrix components to provide a more fetal-like environment for adult tissue repair.

胎儿对伤害的反应方式与 成人：间充质再生过程在缺少 发炎和结疤。我们假设，不同的 细胞外基质，特别是早期出现和延长 维护一个富含透明质酸(HA)的环境，有助于 胎儿伤口中的细胞移动性、细胞增殖和再生。 我们建议描述线性和开放性伤口的愈合过程。 不同胎龄的成年绵羊和胎羊。这只胎羊是 大到足以比得上1厘米的直线伤口，9毫米的开放伤口，以及 邻近未受伤的组织，并记录连续的外观和 修复的细胞和细胞外成分的消失 以下技术：a)包括特殊染色的光学显微镜，b) 利用荧光抗体识别细胞标记物的免疫定位 和细胞外基质成分，c)电子显微镜，d) 一种新的透明质酸结合蛋白对透明质酸的定位 污渍。 这个模型允许我们通过以下方式确定胎龄的影响 比较成人和胎儿在60、100和130岁时的愈合过程 妊娠天数(足月=145天)。胎羊模型可以通过外科手术 被操纵以阐明胎儿环境对愈合的影响： 我们将比较皮肤和内脏伤口的愈合过程 羊水指被排除在羊水之外的人。我们还将比较 60天后成人(母体)皮肤移植到胎儿身上的创面 妊娠(胎儿对皮肤移植耐受到70天)对伤口 在相邻的自体移植的胎儿皮肤上制作。 最近的证据表明，房委会的长期维护是 胎儿伤口愈合。我们将比较成人体内HA的沉积和代谢 不同胎龄的伤口和胎儿伤口。在记录了 在我们的模型中，我们将检查HA沉积的生物化学 通过分析伤口液(从伤口抽取)了解HA的沉积和代谢 钢丝网圆筒)以及血清、尿液和羊水 透明质酸合成、透明质酸酶活性、透明质酸酶 抑制剂，以及新发现的HA刺激和抑制因子。 与炎症和疤痕相关的破坏性临床问题 通过调节细胞外基质可以减轻形成 为成人组织提供更像胎儿一样的环境的组件 修理。