背景:隐性营养不良性大疱性表皮松解症(RDEB)是由COL7A1基因突变引起的严重皮肤脆性疾病,编码VII型胶原蛋白(COL7),用于将表皮附着到真皮的锚定原纤维的主要成分。持续的皮肤糜烂经常导致RDEB患者的顽固性溃疡。脂肪来源的间充质基质细胞(AD-MSC)易于大量收获并且具有低免疫原性。因此,它们适合临床使用,包括涉及同种异体细胞移植的应用。从AD-MSC转分化的角质形成细胞样细胞(KC-AD-MSC)比未分化的AD-MSC表达更多的COL7,并且促进皮肤伤口愈合而减少挛缩。因此,这些细胞可用于RDEB患者的皮肤溃疡治疗。
目的:我们研究了KC-AD-MSCs移植是否改善了免疫缺陷小鼠背部RDEB小鼠模型(col7a1-null)移植皮肤中RDEB表型的严重程度。
方法:将KC-AD-MSCs皮内注射到皮肤移植物周围的区域,7天后重复此程序。再间隔7天后,收获皮肤移植物。
结果:观察到COL7的新沉积和真皮-表皮连接处的锚定原纤维的产生,虽然实验是基于定性的。
结论:KC-AD-MSCs可以纠正COL7功能不全,修复有缺陷/减少的锚定原纤维,改善RDEB患者的皮肤完整性。
BACKGROUND: Recessive dystrophic epidermolysis bullosa (RDEB) is a severe skin fragility disorder caused by mutations in the COL7A1 gene, which encodes type VII collagen (COL7), the main constituent of anchoring fibrils for attaching the epidermis to the dermis. Persistent skin erosions frequently result in intractable ulcers in RDEB patients. Adipose-derived mesenchymal stromal cells (AD-MSCs) are easily harvested in large quantities and have low immunogenicity. Therefore, they are suitable for clinical use, including applications involving allogeneic cell transplantation. Keratinocyte-like cells transdifferentiated from AD-MSCs (KC-AD-MSCs) express more COL7 than undifferentiated AD-MSCs and facilitate skin wound healing with less contracture. Therefore, these cells can be used for skin ulcer treatment in RDEB patients.
OBJECTIVE: We investigated whether KC-AD-MSCs transplantation ameliorated the RDEB phenotype severity in the grafted skin of a RDEB mouse model (col7a1-null) on the back of the immunodeficient mouse.
METHODS: KC-AD-MSCs were intradermally injected into the region surrounding the skin grafts, and this procedure was repeated after 7 days. After a further 7-day interval, the skin grafts were harvested.
RESULTS: Neodeposition of COL7 and generation of anchoring fibrils at the dermal-epidermal junction were observed, although experiments were based on qualitative.
CONCLUSIONS: KC-AD-MSCs may correct the COL7 insufficiency, repair defective/reduced anchoring fibrils, and improve skin integrity in RDEB patients.