恶性黑素瘤与黑素干细胞

恶性黑素瘤是高度转移性肿瘤,对传统的治疗抵抗,黑素瘤的发生涉及遗传和环境因素。大多数黑素瘤为原发性,但部分黑素瘤从黑素细胞痣发展而来。以往认为,长期暴露于紫外线、皮肤黑素细胞逐渐积累致癌基因、肿瘤抑制基因发生突变导致了黑素细胞的增殖,并获得侵袭性和转移的能力,成为黑素瘤。另有假说认为,黑素瘤起源于毛囊外真皮黑素干细胞,紫外线诱导的突变可能会改变正常黑素干细胞自我更新、扩展和分化的过程,导致黑素瘤的形成。深入了解黑素瘤的发生机制,有利于寻求更好的治疗方案。     

Melanocyte melanin augments sparfloxacin-induced phototoxicity.

Quinolone has become one of the common causative agents of drug-induced photosensitive dermatitis, and its phototoxicity has now become a clinical issue. The mechanisms of long-lasting phototoxicity induced by sparfloxacin (SPFX) were investigated using melanotic and amelanotic melanoma cell lines. The sensitivities to SPFX and UVA irradiation up to 6 J/cm2 of both cells were not significantly different. However, the melanotic melanoma cell cultured with 1-150 microg/ml of SPFX showed significantly higher sensitivity to UVA irradiation compared with that of the amelanotic melanoma cell. By pulse culture with SPFX, the bound SPFX level of melanotic cell line was 10-20 times higher than that of the amelanotic cell line. These data strongly suggest that the melanin in melanocytes and keratinocytes accumulates the antibacterial quinolone and increases its tissue concentration in the basal epidermis and contributes to the long-lasting photo-injury and liquefaction degeneration of the basal cells in antibiotic quinolone phototoxic dermatitis.     

黑素细胞与SCF/KIT途径

人黑素细胞来源于神经嵴干细胞 ,在胚胎形成期迁移到真皮 ,最后定位于表皮基底层、毛囊等处 ;SCF/KIT途径对黑素细胞的生存、发育、迁移、分化、增殖都起了关键作用 ,一旦该途径失调就会导致斑驳病、色素性荨麻疹等 ,而有些表现为皮肤色素异常的疾病如白癜风、系统性硬皮病等又伴有SCF/KIT途径的失调。     

Comparative Study of Efficacy of Epidermal Melanocyte Transfer Versus Hair Follicular Melanocyte Transfer in Stable Vitiligo

Background:Vitiligo surgery has come up a long way from punch skin grafts to epidermal cell suspension and latest to the extracted hair follicle outer root sheath cell suspension (EHFORSCS) transplantation. The progressive development from one technique to the other is always on a quest for the best. In the latest development, EHFORSCS, which is an enriched source of follicular inactive melanocyte (melanocyte stem cells), seems to be a good addition to the prevailing cell-based therapies for vitiligo. However, it needs to be explored further in larger, clinical trials.Methodology:A total of 11 patients with sixty stable vitiligo sites attending dermatology outpatient department were included for the open-labeled, prospective, comparative study. The sites were sequentially distributed into two groups of thirty each. Sites of one group were subjected to epidermal melanocyte transfer (EMT) and the others to hair follicular melanocyte transfer (HFMT). Response to treatment was evaluated on the basis of degree of repigmentation; final evaluation of area of involvement was done after completion of 6 months.Results:At the end of 6 months, repigmentation >90% was observed in 83.33% patches of EMT group and 43.33% in HFMT group. Repigmentation >75% was observed in 90% of patches in Group A and 43.34% of patches in Group B, respectively. There was statistically significant difference in the overall pigmentation between these two groups.Conclusion:Both noncultured autologous epidermal cell suspension transfer and noncultured EHFORSCS transfer are safe and effective surgical modalities in the management of stable vitiligo though EMT has shown a better response in the present study. Outer root sheath cell suspension transfer is a novel, minimally invasive technique in its nascent stage in the surgical management of vitiligo which requires further larger clinical trials for evaluation of its efficacy.     

Melanocyte stem cells and hair graying

Objectives

To explore the relationship between melanocyte stem cells in the hair follicle bulge and hair graying so as to fully understand their key role in the pathogenesis of hair graying.

Methods

The published articles about “hair graying, hair color, pigmentation disorders” and “melanocyte stem cells, melanocyte” were searched and analyzed in PubMed to explore their relationship.

Results

Melanocytes in hair bulb are involved in the pathogenesis of hair graying as well as the melanocyte stem cells in hair follicle bulge also play important roles in the formation of hair graying through some ways.

Conclusion

Loss of melanocyte stem cells in hair follicle bulge is one of the main reasons of hair graying, and more researches are needed to explain the underlying mechanisms of ectopic differentiation of melanocyte stem cells in different individual.     

Melanocyte mitosis in UVB-irradiated mouse skin.

Little is known about the mitotic activity of the epidermal melanocyte population. Vincristine sulphate has now been used in vivo to study the frequency of mitosis of epedermal melanocytes in the ear skin of C57BL mice. It is shown that there is continuous formation of new melanocytes in unstimulated skin due to mitosis of pigment-producing epidermal melanocytes. The increase in this mitotic rate following daily UVB irradiation suggests that this is a major mechanism responsible for the UV-induced increase in the epidermal melanocyte population.     

A Study of Normal Epidermal Melanocyte Distribution

Objective::To elucidate the epidermal melanocyte distribution according to sex, age, and body part with the goal of providing benchmark data for the diagnosis a...     

Melanocyte autologous grafting for treatment of leukoderma

Patients with three types of leukoderma--vitiligo, idiopathic guttate hypomelanosis, and postinflammatory leukoderma--had successful repigmentation after transplantation of autologous melanocytes. The procedure was performed easily by producing blisters on normal skin and on depigmented lesions. Blisters were produced by suction or by freezing with liquid nitrogen. The roof of the blister from donor skin was grafted to the raw surface of the recipient site. Repigmentation was visible within 7 to 14 days. Direct immunofluorescence staining with bullous pemphigoid antibodies suggested that the separation of the epidermis from the dermis occurs within the lamina lucida. Histochemical studies confirmed the absence of dopa-positive cells in the areas of leukoderma prior to grafting. Melanocytes were present in the successful grafts.     

Melanocyte biology and its implications for the clinician

Epidermal and follicular melanocytes are neural crest derived cells that are in close contact with surrounding keratinocytes. By producing melanin in specialized organelles, the melanosomes, and transferring it to the keratinocytes, human skin becomes pigmented. Establishment of cultures of human melanocytes and an increasing interest in photo-carcinogenesis/photoaging have led to an explosion of knowledge concerning the biology of melanocytes.     

Melanocyte receptors: clinical implications and therapeutic relevance

The activation or the inhibition of melanocyte-specific receptors offers novel means of augmenting normal melanocyte function, skin color, and photoprotection, or treating melanocytic disorders, namely at this time, metastatic melanoma. Melanocyte-specific receptors include melanocortin-1 (MCR1) and melatonin receptors. Other receptors that play an important role in melanoma progression are G-protein couple receptors such as Frizzled 5 and receptor tyrosine kinases such as c-Kit and hepatocyte growth factor (HGF) receptor. These receptors activate two crucial cell-signaling pathways, RAS/RAF/MEK/ERK and PI3K/AKT, integral to melanoma cell survival, and can serve as targets for therapy of disseminated melanoma. Activation of death receptors is another pathway that can be exploited with targeted therapeutics to control advanced melanoma. This article reviews the current understanding of melanocyte receptors, their agonists and inhibitors, and their potential to treat the melanocytic pathology.     

白癜风相关黑素细胞膜抗原的检测及分析

目的 检测和分析白癜风相关的黑素细胞膜抗原,为纯化和克隆白癜风相关的黑素细胞膜抗原打下基础。方法 用活细胞ELISA法筛选白癜风血清,获得抗黑素细胞膜的强阳性IgG血清;体外培养正常人黑素细胞,裂解黑素细胞并作免疫印迹。共检测分析了30例强阳性白癜风血清。结果 免疫印迹显示,全部被筛选出的强阳性血清均有阳性条带,对照仅1例阳性(10%);抗体结合多种抗原成分,相对分子质量约为150000、90000、75000、50000、40000~45000。各个条带阳性率分别为70%、60%、83%、16%、23%。结论 白癜风患者血清中存在抗黑素细胞膜抗体,膜抗原相对分子质量主要为150000、90000、75000,以往发现的一些小分子抗原可能为大分子抗原的降解产物。     

单味中药对黑素细胞黏附和迁移的影响

目的　探讨单味中药乙醇提取物对体外培养黑素细胞黏附、迁移的影响。方法　 14味中药分别用 70 %乙醇提取 ,正常人黑素细胞来自包皮环切术切取的包皮 ,用包被纤维连接蛋白的 48孔培养板检测黑素细胞黏附 ,用微孔膜研究黑素细胞迁移。结果　丹参、菟丝子和红花的乙醇提取物可促进黑素细胞黏附 ,刺蒺藜和黄芪可促进黑素细胞迁移 ,而补骨脂、女贞子和白芷可同时促进黑素细胞黏附和迁移。结论　丹参、菟丝子、红花、刺蒺藜、黄芪、补骨脂、女贞子和白芷可能通过增加黑素细胞黏附和 /或改变迁移途径对白癜风产生治疗作用