Η φαλάκρα –εδώ αναφέρεται ως ανδρογενής αλωπεκία- οφείλεται σε αδυναμία των βλαστικών κυττάρων να συντηρήσουν λειτουργικά θυλάκια ή τρίχες. Αυτό θεωρείται ήδη αναστρέψιμο υποστηρίζουν επιστήμονες-ερευνητές που ανήκουν στην ομάδα ενός Ελληνα δερματολόγου Γιώργου Κοτσαρέλη, ο οποίος τρία χρόνια πριν είχε δημιουργήσει τριχοθύλακες. Οι τριχοθύλακες των τριχών σχηματίζονται από κύτταρα, που «κατάγονται» από βλαστικά κύτταρα δέρματος των οποίων η αδυναμία να εξελιχθούν σε πρόδρομα κύτταρα προκαλεί την φαλάκρα.
(όλο το δημοσίευμα)
Bald scalp
in men with androgenetic alopecia retains hair follicle stem cells but lacks
CD200-rich and CD34-positive hair follicle progenitor cells
Adult
somatic stem cells act as the ultimate source of cells for self-renewing
epithelia during homeostasis and wound healing. In the skin, a portion of the
hair follicle known as the bulge contains a reservoir of small quiescent stem
cells that divide during the onset of each new hair growth cycle or in response
to wounding (1–4). Here, we address whether bald scalp in androgenetic alopecia
(AGA; also referred to as male pattern baldness) lacks hair follicle stem or
progenitor cells.
In AGA,
large terminal follicles diminish in size with time, and the resulting
miniaturized follicle eventually produces a microscopic hair. Miniaturization
of the follicle takes place as the hair follicle cycles. All follicles
continuously cycle from a growing stage (anagen), to an involutional stage
(catagen), and then to a resting stage (telogen), before again entering anagen
(5). In AGA, the new lower hair follicle that forms at anagen onset is smaller
than its predecessor. Testosterone is necessary for miniaturization, and 5-α-reductase type II inhibitors, which
block conversion of testosterone to its more active form, dihydrotestosterone,
delay progression of AGA (6). Little else is understood about the cause of AGA.
Stem cells
responsible for hair follicle cycling reside in the hair follicle bulge of both
mouse and human skin (7, 8). Bulge cells generate all the epithelial lineages
within the follicle (9), and their selective destruction leads to loss of the
follicle (2). Isolated murine bulge cells, when combined with neonatal dermal
cells in a skin reconstitution assay, re-form the entire cutaneous epithelium,
including hair follicle, epidermis, and sebaceous gland (9, 10). Bulge cells
give rise to a progenitor population called the secondary germ cells, which
reside adjacent to the bulge during telogen and produce the new hair shaft at
anagen onset. A new secondary germ regenerates from the bulge with each new
hair cycle (1, 11).
Human hair
follicle bulge cells possess stem cell characteristics similar to those of
mouse bulge cells. Proliferation studies on mouse skin and on human scalp
grafted to immunodeficient mice localize quiescent cells to the bulge (3, 12). Gene
expression profiles from isolated mouse bulge cells and microdissected human
bulge cells share similar patterns (4, 9, 13). However, to our knowledge no
human hair follicle cells have been reported to form hair follicles in reconstitution
assays, likely because of limitations of the xenograft system. In vitro
proliferation assays indicate that basal bulge cells possess a high
proliferative potential consistent with a stem cell phenotype (13, 14).
Global gene
expression studies of isolated bulge cells from both mice and humans indicate
preferential expression of the intermediate filament protein KRT15 and the cell
surface marker CD200 (9, 13). CD34 expression marks hair follicle bulge cells
in mouse, but not human, epithelium (7, 15). In humans, CD34 expression is
confined to cells immediately below the bulge in the outer root sheath of the
anagen hair follicle (7, 14, 16). These cells undergo apoptosis at the end of
anagen, but cells from here form high numbers of colonies in in vitro assays
and are considered to be a progenitor population derived from the bulge (14,
17). Thus, the use of these markers allows for assessment of stem and
progenitor cell populations in human scalp.
Here we
analyzed KRT15, CD200, and CD34 expression with flow cytometry to assess the
stem and progenitor cell compartments in bald and haired (i.e., non-bald) scalp
from individuals with AGA. Surprisingly, we found that the stem cell population
was maintained in bald scalp. However, CD200hiITGA6hi and CD34hi cells were
greatly diminished. These lost cells likely represent early progeny of stem
cells, based on their position in the follicle, stem cell marker expression
levels, cell size, and cell cycle state. Functionally, an analogous murine
CD200hiItga6hi population was capable of regenerating an entire hair follicle,
consistent with a progenitor cell phenotype. These results suggest that loss of
progenitor cells, but not stem cells, contributes to human male pattern
baldness.
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