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用于工程化皮肤替代物移植的培养人黑素细胞在无胸腺小鼠中的致瘤性测试

Tumorigenicity Testing in Athymic Mice of Cultured Human Melanocytes for Transplantation in Engineered Skin Substitutes.

作者信息

Boyce Steven T, Zimmerman Rachel L, Supp Dorothy M

机构信息

Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, OH, USA.

出版信息

Cell Transplant. 2015;24(8):1423-9. doi: 10.3727/096368914X683052. Epub 2014 Jul 23.

DOI:10.3727/096368914X683052
PMID:25199067
Abstract

Autologous engineered skin substitutes (ESS) have been shown to close excised, full-thickness burns, but are consistently hypopigmented due to depletion of human melanocytes (hM) during culture of keratinocytes. Hypothetically, addition of hM to ESS may restore uniform pigmentation, but may also promote neoplasia and tumor formation. To evaluate this risk, 16 strains of hM were isolated and propagated in selective culture medium, then injected subcutaneously into athymic mice (1 × 10(7) hM/animal; n = 6/strain) and followed for 24 weeks. Human melanoma cells (SK-Mel-2, SK-Mel-5) served as positive controls. No detectable tumors formed from hM strains derived from normal skin. In contrast, SK-Mel-2 formed tumors in 50% of mice, and SK-Mel-5 formed tumors in 83% of mice. Histopathology confirmed the tumorigenic anatomy of the controls and the presence of hM that were not tumorigenic in the test groups. These results support the safety of cultured hM for transplantation to restore uniform skin pigmentation in wounds closed with ESS.

摘要

自体工程皮肤替代物(ESS)已被证明可闭合切除的全层烧伤创面,但由于角质形成细胞培养过程中人类黑素细胞(hM)的消耗,其色素沉着始终不足。从理论上讲,向ESS中添加hM可能会恢复均匀的色素沉着,但也可能促进肿瘤形成。为评估这种风险,分离出16株hM并在选择性培养基中进行培养,然后皮下注射到无胸腺小鼠体内(每只动物注射1×10⁷个hM;每个菌株n = 6只),并持续观察24周。人黑色素瘤细胞(SK-Mel-2、SK-Mel-5)作为阳性对照。源自正常皮肤的hM菌株未形成可检测到的肿瘤。相比之下,SK-Mel-2在50%的小鼠中形成肿瘤,SK-Mel-5在83%的小鼠中形成肿瘤。组织病理学证实了对照组的致瘤解剖结构以及测试组中未致瘤的hM的存在。这些结果支持了培养的hM用于移植以恢复用ESS闭合伤口处皮肤均匀色素沉着的安全性。

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