Department of Tissue Engineering, Nicolaus Copernicus University in Torun, Bydgoszcz, Poland.
Cell Transplant. 2010;19(5):639-43. doi: 10.3727/096368910X491798. Epub 2010 Mar 26.
Cultured human melanocytes are increasingly being used in the treatment of vitiligo. The growth media contain various types of mitogenic factors, both recombinant human (e.g., rhbFGF and rhSCF) and synthetic (e.g., TPA). High concentrations of mitogenic factors accelerate the cell cycle, and consequently may increase the risk of carcinogenesis of transplanted cells. Mutations of genes of the RAS/RAF/MEK/ERK signaling pathway are very often found in the early stages of the development of melanoma. TPA is considered to be an oncogenic factor, but so far there is no evidence to show that it is responsible for damage to the genetic material of cultured melanocytes. The aim of our study was to assess the risk of the development of mutations in selected genes of the RAS/RAF/MEK/ERK signaling pathway during the culturing of melanocytes in various growth media. Based on the results obtained, it can be concluded that TPA and high concentrations of other growth factors intensify the proliferation of melanocytes, without the risk of damage to the HRAS (exon 1 and 2), KRAS (exon 1 and 2), NRAS (exon 1 and 2), and BRAF (exon 11 and 15) genes. In order to assess the total safety of the transplantation of cultured melanocytes, it is necessary to carry out further studies on other signaling pathways as well as carry out biological tests on an animal model.
培养的人类黑素细胞越来越多地被用于治疗白癜风。生长培养基中含有各种有丝分裂原因子,包括重组人(例如 rhbFGF 和 rhSCF)和合成的(例如 TPA)。高浓度的有丝分裂原因子会加速细胞周期,从而可能增加移植细胞致癌的风险。RAS/RAF/MEK/ERK 信号通路的基因突变在黑色素瘤的早期阶段非常常见。TPA 被认为是一种致癌因素,但迄今为止尚无证据表明它会导致培养的黑素细胞遗传物质受损。我们的研究目的是评估在不同生长培养基中培养黑素细胞时,RAS/RAF/MEK/ERK 信号通路中选定基因发生突变的风险。基于获得的结果,可以得出结论,TPA 和其他高浓度生长因子会增强黑素细胞的增殖,而不会导致 HRAS(外显子 1 和 2)、KRAS(外显子 1 和 2)、NRAS(外显子 1 和 2)和 BRAF(外显子 11 和 15)基因受损。为了评估培养的黑素细胞移植的总体安全性,有必要对其他信号通路进行进一步研究,并在动物模型上进行生物学测试。