异基因造血细胞移植的免疫耐受支持隐性营养不良性大疱性表皮松解症慢性伤口的供体表皮移植。
Immune tolerance of allogeneic haematopoietic cell transplantation supports donor epidermal grafting of recessive dystrophic epidermolysis bullosa chronic wounds.
作者信息
Ebens C L, McGrath J A, Riedl J A, Keith A R, Lilja G, Rusch S, Keene D R, Tufa S F, Riddle M J, Shanley R, Van Heest A E, Tolar J
机构信息
Division of Blood and Marrow Transplantation, Department of Pediatrics, Medical School, University of Minnesota, Minneapolis, MN, USA.
St John's Institute of Dermatology, King's College London, London, England.
出版信息
Br J Dermatol. 2021 Jun;184(6):1161-1169. doi: 10.1111/bjd.19503. Epub 2020 Dec 14.
BACKGROUND
Chronic wounds, a common morbidity in recessive dystrophic epidermolysis bullosa (RDEB), lack definitive therapies.
OBJECTIVES
To assess allogeneic epidermal skin grafts in terms of wound healing and durability over time.
METHODS
In a prospective, open-label clinical trial for postallogeneic haematopoietic cell transplantation (post-alloHCT) patients with RDEB, up to nine chronic wounds per patient were grafted over 1 year. Epidermal grafts measuring 5 cm were obtained from related alloHCT donors in the outpatient setting using the CELLUTOME Epidermal Harvesting System. Wounds were photographed and symptom inventories completed at baseline and 6, 12 and 52 weeks after grafting. The trial was registered at ClinicalTrials.gov (NCT02670837).
RESULTS
Between August 2016 and January 2019, eight patients with RDEB received a total of 35 epidermal allografts at a median of 1157 days (range 548-2884) post-alloHCT. The median (interquartile range) percentage reductions in wound surface area were 75% (52-94), 95% (72-100) and 100% (97-100) at 6, 12 and 52 weeks postgraft, respectively, each significantly reduced from baseline (P < 0·001). Donor harvest sites healed quickly without scarring. Biopsy evaluation at 1 year of an epidermal allograft site revealed wildtype type VII collagen (immunofluorescence), anchoring fibrils (electron microscopy), and full-thickness skin whole-DNA donor chimerism of 42% (compared with 16% in concurrently biopsied native skin). This strategy subsequently supported release of RDEB pseudosyndactyly.
CONCLUSIONS
The immune tolerance established by alloHCT supports successful adoptive transfer of donor epidermal grafts. Persistence of donor grafts in a single patient beyond 1 year and observed migration of donor-grafted cells into adjacent wound suggest that epidermal allografts include nonterminally differentiated cells and/or trigger recruitment of donor bone-marrow-derived cells to mediate wound healing.
背景
慢性伤口是隐性营养不良性大疱性表皮松解症（RDEB）的常见病症，目前缺乏有效的治疗方法。
目的
评估异体表皮移植在伤口愈合及长期耐久性方面的效果。
方法
在一项针对接受异基因造血细胞移植（alloHCT）后的RDEB患者的前瞻性、开放标签临床试验中，每位患者在1年内最多可接受9处慢性伤口的移植。使用CELLUTOME表皮采集系统在门诊环境中从相关alloHCT供体获取5厘米大小的表皮移植物。在基线时以及移植后6、12和52周对伤口进行拍照并完成症状清单。该试验已在ClinicalTrials.gov（NCT02670837）注册。
结果
2016年8月至2019年1月期间，8例RDEB患者在alloHCT后中位时间1157天（范围548 - 2884天）共接受了35次表皮异体移植。移植后6、12和52周时，伤口表面积减少的中位（四分位间距）百分比分别为75%（52 - 94）、95%（72 - 100）和100%（97 - 100），均较基线时显著降低（P < 0.001）。供体采集部位愈合迅速且无瘢痕形成。对一处表皮异体移植部位进行1年的活检评估显示有野生型VII型胶原蛋白（免疫荧光法）、锚定原纤维（电子显微镜检查），全层皮肤全DNA供体嵌合率为42%（同期活检的正常皮肤为16%）。该策略随后促使RDEB假性并指松解。
结论
alloHCT建立的免疫耐受支持供体表皮移植物的成功过继转移。供体移植物在单一患者体内持续超过1年，且观察到供体移植细胞迁移至相邻伤口，这表明表皮异体移植包含未终末分化的细胞和/或触发了供体骨髓来源细胞的募集以介导伤口愈合。
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