Hoang M P, Keady M, Mahalingam M
Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Br J Dermatol. 2009 Mar;160(3):609-15. doi: 10.1111/j.1365-2133.2008.09015.x. Epub 2009 Jan 27.
Although the pathogenesis of most primary scarring alopecias is poorly understood, recent studies implicate the bulge region as a possible target.
To corroborate these results, we ascertained involvement of follicular bulge stem cells using a panel of antibodies that putatively targeted the same.
Antibodies used included anticytokeratin (CK) 15, CD34 and nestin on vertical and horizontal tissue sections of 50 cases of scarring and 34 cases of nonscarring alopecia.
Comparing expression of these markers in scarring vs. nonscarring alopecia, CK15 was noted in the follicular bulge region in 23 of 43 (53%) vs. 27 of 27 (100%) cases and in the peripheral layer of the outer root sheath (ORS) (upper two-thirds of the follicle) in 50 of 50 (100%) vs. 34 of 34 (100%) cases; CD34 was noted in the peripheral layer of the ORS (below pilar muscle attachment) in 24 of 35 (69%) vs. 18 of 18 (100%) cases; and nestin was noted in the infundibular region in 18 of 46 (39%) vs. seven of 32 (22%) cases and in the inner aspect of the ORS (below pilar muscle attachment) in eight of 31 (26%) vs. 23 of 23 (100%) cases.
Our findings of differential follicular localization of stem cells underscore follicular progenitor cell heterogeneity and suggest the target in scarring alopecia is not merely follicular bulge stem cells but involves stem cells in the inner and outer aspect of the ORS. Enhanced expression of nestin in the infundibular region in scarring alopecia indicates availability of an accessible, in vivo niche of potential utility as an autologous source of stem cells for therapeutic application.
尽管大多数原发性瘢痕性脱发的发病机制尚不清楚,但最近的研究表明毛囊隆突区可能是一个靶点。
为了证实这些结果,我们使用一组假定靶向相同区域的抗体来确定毛囊隆突干细胞是否参与其中。
所使用的抗体包括抗细胞角蛋白(CK)15、CD34和巢蛋白,应用于50例瘢痕性脱发和34例非瘢痕性脱发的垂直和水平组织切片。
比较这些标志物在瘢痕性脱发和非瘢痕性脱发中的表达,CK15在43例中的23例(53%)的毛囊隆突区有表达,而在27例(100%)的非瘢痕性脱发中均有表达;在毛囊外根鞘(ORS)外周层(毛囊上三分之二),50例(100%)瘢痕性脱发中有50例表达,34例(100%)非瘢痕性脱发中均有表达;CD34在ORS外周层(毛囊肌附着点以下),35例中的24例(69%)瘢痕性脱发中有表达,18例(100%)非瘢痕性脱发中均有表达;巢蛋白在漏斗部区域,46例中的18例(39%)瘢痕性脱发中有表达,32例中的7例(22%)非瘢痕性脱发中有表达;在ORS内侧(毛囊肌附着点以下),31例中的8例(26%)瘢痕性脱发中有表达,23例(100%)非瘢痕性脱发中均有表达。
我们关于干细胞在毛囊中定位差异的研究结果强调了毛囊祖细胞的异质性,并表明瘢痕性脱发的靶点不仅是毛囊隆突干细胞,还涉及ORS内外侧的干细胞。瘢痕性脱发漏斗部区域巢蛋白表达增强,表明存在一个可及的、体内的小生境,有可能作为治疗应用的自体干细胞来源。