人头发毛囊外根鞘中有二个不同的K19阳性区:干细胞储库的统一假说?

至今，人生长期毛囊中干细胞的定位依靠三种互补的检查方法：即检测缓慢周期生长细胞、高集落形成细胞和分化细胞的免疫组化染色。由于干细胞既可以是位于隆突部位的长期标记的保留细胞，也可以是位于毛囊下三分之一处的高集落形成细胞，所以这些技术往往产生相互矛盾的结果。为了阐明毛发生长周期中人毛囊干细胞的分布情况，我们研究了通常被认为是上皮干细胞标志的细胞角蛋白19(K19)的表达。发现人生长期毛囊中有两个干细胞储库，分别位于毛囊的上、下三分之一处。这两个储库在毛囊的退行期一休止期的过渡阶段发生融合，在新形成的生长期毛囊中再次分开。     

毛囊干细胞研究进展

干细胞是一类具有高度增殖潜能和终生无限的自我更新能力的细胞亚群,毛囊干细胞主要位于毛囊隆突部位,能表达β1整合素,角蛋白(Keratin)K15、K19,转录因子p63等特异性表面标记,据此可以对其进行鉴定和分离。研究毛囊干细胞如何增殖与分化及其调控机制,不但有实现以毛囊干细胞作为种子细胞构建组织工程化皮肤及毛囊来分别治疗皮肤缺损和脱发的重大意义,而且也为治疗某些棘手的皮肤、毛囊疾病带来了希望。     

真皮干细胞在毛囊周期中的作用

毛囊由表皮(上皮)及真皮(间充质)组成,它们之间的相互作用在毛囊的形态发生及生长中发挥重要作用,二者之间相互作用是毛囊成功重建的关键因素.在毛发形成过程中,真皮细胞是诱导者,上皮细胞是应答者.真皮鞘和毛乳头内存在毛囊真皮干细胞,属于成体干细胞,具有慢周期、未分化、自我更新和体外增殖能力强的特点.真皮鞘中的真皮干细胞较长寿,可以历经几个毛囊周期,重建真皮鞘.在毛囊周期的生长期,真皮鞘中的干细胞产生新细胞提供给毛乳头;在退行期,真皮干细胞子代移出毛乳头或死亡.毛囊真皮细胞对于损伤和疾病之后的毛囊重建及修复具有重要意义.     

毛囊干细胞及其微环境在毛囊衰老中作用的研究进展

随着人体各器官机能逐渐老化,头发也渐显花白和脱落,成为人体衰老的最突出特征之一。毛发的形态与毛囊的生长发育相关。毛囊隆突部干细胞和壁龛微环境内外调控因素的相互作用,控制毛囊干细胞的增殖和分化,影响其自身稳定状态。毛囊干细胞衰老,DNA损伤效应累积,毛囊休止期时间延迟,继而毛发周期改变,毛囊干细胞逐渐分化为表皮细胞,具体表现为衰老性脱发和衰老相关毛发灰白。毛囊干细胞微环境损伤和信号转导途径改变影响毛囊衰老进程。     

表皮干细胞与表皮肿瘤

表皮干细胞具有无限增殖及多向分化的特性，其子代细胞可以形成角质形成细胞、毛囊、皮脂腺的分化细胞。肿瘤一般起源于单个发生癌性突变的细胞，表皮干细胞很可能是各种类型表皮肿瘤发生的主要靶细胞，分化细胞则能通过影响肿瘤干细胞的克隆扩增，对肿瘤的发生起重要作用。     

毛囊间充质干细胞的研究进展

 毛囊间充质干细胞（HFMSCs）是一类具有自我再生能力、高度增殖潜能、可多向分化且来源丰富的慢周期标记滞留细胞,可促进表皮、毛囊和皮脂腺再生。得益于其来源丰富、易获得、可于体外扩增、无需基因操作、不会形成肿瘤和无伦理限制等特点,毛囊间充质干细胞在再生医学中具有重要优势。Wnt、Shh、Notch和BMP等信号通路之间的协同和拮抗作用在干细胞稳态调节、表皮发育和毛囊再生过程中发挥至关重要的作用,这些途径的失调可能导致毛发脱落或者肿瘤的发生。本文综述毛囊间充质干细胞的分类及其特异性生物标记物、毛囊间充质干细胞的活化以及影响毛发再生的生物分子途径,为毛发疾病的治疗提供新的线索和靶点。     

表皮干细胞的研究进展

干细胞是一类具有高度增殖潜能和无限自我更新能力的细胞亚群。角质形成细胞干细胞主要存在于毛囊隆突部，也见于毛囊间表皮网嵴的底部，其特征为慢周期及高度的增殖潜能，它能表达某些整合素亚单位，并可与细胞外基质发生快速粘连，据此特性可将其分离纯化。角质形成细胞干细胞不仅在表皮及其附属器的组织发生学、银屑病的发病机理中具有重要作用，也是肿瘤发生及基因治疗的重要靶细胞。     

毛囊干细胞与组织工程研究进展

毛囊干细胞研究取得突破性进展的标志是由孙同天、Lavker和Cotsarelis等提出了隆突激活假说,明确了其定位的部位,是少数几种成体干细胞首先被明确定位的干细胞之一,并逐步得到了验证。毛囊干细胞不仅可以分化为毛囊上皮细胞,而且可以分化为皮脂腺细胞、表皮角质形成细胞,其分化过程是干细胞分化为短暂倍增细胞,最后分化为终末分化细胞。近年来进一步证明了毛囊隆突部也是多种干细胞的居住地,包括黑素干细胞,和毛囊干细胞存在同步化激活的机制。Wnt/β-catenin是毛囊发育、再生循环的基本信号通路,使毛囊在再生过程出现着色一致的毛发。诱导和重建毛囊形成是组织工程皮肤最主要的目标之一,毛乳头细胞的凝集性生长特性是诱导毛囊形成的条件,因此,维持毛乳头细胞凝集性生长特性主要有细胞团块法、低黏附性培养板(或高分子材料膜)法、悬滴培养法和胶原凝胶成球法,以实现体外重建毛乳头的目的。毛囊组织工程在体外还不能真正诱导形成,现有的毛囊再生或新生的成功方法还是须移植到动物体内,才能形成完整毛囊并产生毛发。主要方法有移植小室法、混合游离细胞注射法和皮瓣法。诱导毛囊形成比较成功的细胞是啮齿类动物来源的胚胎或新生鼠毛囊细胞和人胚胎毛囊细胞,成年人头皮毛囊来源细胞目前仍未能诱导出毛囊新生或再生。     

毛囊干细胞在脱发性疾病中的研究进展

脱发性疾病在临床比较常见,一般按临床表现和毛发是否可再生而将脱发分为瘢痕性脱发和非瘢痕性脱发,每种均包含了多种不同的脱发性疾病。目前脱发性疾病的发病机制仍不甚清楚。毛囊干细胞位于毛囊隆突区,其周期性地增殖和分化维持了毛发的正常生长、脱落与更替。研究表明,毛囊干细胞的损伤或缺失很可能参与了某些脱发性疾病尤其是瘢痕性脱发的发病过程。     

人毛囊干细胞的定位及增殖特性

目的 探讨人毛囊干细胞定位和增殖特性.方法 取人枕部头皮毛囊进行角蛋白19(K19)免疫组化染色,并测量阳性段距毛囊下端的距离;将包含毛球部上方阳性段的毛囊上皮组织分别置于含有和不含有间质细胞的凝胶表面气液界面培养,当出现增殖灶时,测量其距毛囊下端的距离,分析K19阳性部位与培养出现的增殖灶之间的关系,并通过透射电镜观察增殖灶的超微结构.结果 人枕部头皮毛囊有两个K19阳性区域,即隆突部和毛球部上方一段外根鞘,毛囊下段上皮组织只在含有间质细胞的凝胶表面培养时毛球部上方出现一增殖灶,统计学分析支持毛球部上方的K19阳性部位和毛囊下段上皮组织培养出现的增殖灶为同一部位.透射电镜显示增殖灶含有幼稚细胞、成熟角质形成细胞和凋亡细胞.结论 人头皮毛囊可能有两个干细胞库,即隆突部和球部上方外根鞘的一个局限区域,干细胞的增殖需要间质细胞(如毛乳头细胞)的存在,增殖的干细胞可能向形成新的干细胞、成熟角质形成细胞和凋亡细胞三个方向演变.     

New fillers for the new man

ABSTRACT:  Two new collagen-based lidocaine-containing dermal fillers, ArteSense™/ArteFill™ (Artes Medical, San Diego, CA) and Evolence® (Colbar LifeScience Ltd., Herzliya, Israel), have proved to be of particular interest to men, many of whom seek a long-lasting or permanent correction. ArteFill™ has been available in the United States since 2006, and it is expected that Evolence® will reach the American market in 2008. The properties of the two products will be described, and experience based on the administration of many hundreds of syringes of both products by a Canadian dermatologist will be detailed here, with tips and precautions to optimize patient outcomes.     

Outcomes and adverse effects of ablative vs nonablative lasers for skin resurfacing: A systematic review of 1093 patients

It is generally believed that ablative laser therapies result in prolonged healing and greater adverse events when compared with nonablative lasers for skin resurfacing. To evaluate the efficacy of ablative laser use for skin resurfacing and adverse events as a consequence of treatment in comparison to other modalities, a PRISMA‐compliant systematic review (Systematic Review Registration Number: 204016) of twelve electronic databases was conducted for the terms “ablative laser” and “skin resurfacing” from March 2002 until July 2020. Studies included meta‐analyses, randomized control trials, cohort studies, and case reports to facilitate evaluation of the data. All articles were evaluated for bias. The search strategy produced 34 studies. Of 1093 patients included in the studies of interest, adverse events were reported in a total of 106 patients (9.7%). Higher rates of adverse events were described in nonablative therapies (12.2% ± 2.19%, 31 events) when compared with ablative therapy (8.28% ± 2.46%, 81 events). 147 patients (13.4%) reported no side effects, 68 (6.22%) reported expected, transient self‐resolving events, and five (0.046%) presented with hypertrophic scarring. Excluding transient events, ablative lasers had fewer complications overall when compared with nonablative lasers (2.56% ± 2.19% vs 7.48% ± 3.29%). This systematic review suggests ablative laser use for skin resurfacing is a safe and effective modality to treat a range of pathologies from photodamage and acne scars to hidradenitis suppurativa and posttraumatic scarring from basal cell carcinoma excision. Further studies are needed, but these results suggest that ablative lasers are a superior, safe, and effective modality to treat damaged skin.     

Genetic alterations in RAS‐regulated pathway in acral lentiginous melanoma

Studies integrating clinicopathological and genetic features have revealed distinct patterns of genomic aberrations in Melanoma. Distributions of BRAF or NRAS mutations and gains of several oncogenes differ among melanoma subgroups, while 9p21 deletions are found in all melanoma subtypes. In the study, status of genes involved in cell cycle progression and apoptosis was evaluated in a panel of 17 frozen primary acral melanomas. NRAS mutations were found in 17% of the tumors. In contrast, BRAF mutations were not found. Gains of AURKA gene (20q13.3) were detected in 37.5% of samples, gains of CCND1 gene (11q13) or TERT gene (5p15.33) in 31.2% and gains of NRAS gene (1p13.2) in 25%. Alterations in 9p21 were identified in 69% of tumors. Gains of 11q13 and 20q13 were mutually exclusive, and 1p13.2 gain was associated with 5p15.33. Our findings showed that alterations in RAS‐related pathways are present in 87.5% of acral lentiginous melanomas.     

Self‐resolving superficial primary cutaneous mucormycosis in a 7‐week‐old infant

A 7‐week‐old girl, born at 30 weeks' gestational age, presented to clinic for evaluation of a crop of vesicular lesions that were noted after removal of a bandage that had been in place for 4 days. A punch biopsy of the lesion revealed fungal elements that were later identified as Rhizopus spp. The lesion began to self‐resolve, and no further treatment was needed, with full resolution of the lesion by 1 month after presentation. Clinicians should be aware of the variable presentations of mucormycosis and consider fungal infection in the differential diagnosis when evaluating vulnerable patients with skin eruptions.     

Pathogenic role of IL-17 in psoriasis and psoriatic arthritis

Psoriasis is a chronic inflammatory skin disorder resulting from a complex network of cytokines and chemokines produced by various immune cell types and tissue cells. Emerging evidence suggests a central role of IL-17 and IL-23/T17 axis in the pathogenesis of psoriasis, giving a rationale for using IL-17-blocking agents as therapeutics.Three agents targeting IL-17 signaling are being studied in Phase III clinical trials: secukinumab and ixekizumab (IL-17 neutralizing agents), and brodalumab (IL-17 receptor antagonist). Preliminary results are highly promising for all anti-IL17 agents, creating fair expectations on this class of agents as the new effective therapeutic approach for the treatment of psoriasis.