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Dermatopathology: Practical & Conceptual April - June 1995
Searching for Diogenes: Bulge-Activation Hypothesis Part II—The Bulge is Not a Bulge
Cosimo Misciali, MD
A. Bernard Ackerman, MD
1927 Felix Pinkus
1951 Hermann Pinkus
1958 Hermann Pinkus
1961 Sanderson & Thiede
1987 Headington & Astle
1990 Leshin & White
1990 Cotsarelis, Sun, Lavker
1991 Sun, Cotsarelis, Lavker
1991 Lavker, Cotsarelis, Wei, Sun
1991 Lane, Wilson, Hughes, Leigh
1992 Jaworsky, Kligman, Murphy
1993 Yang, Lavker, Sun
1993 Lavker, Miller, Wilson, Costarelis, Wei, Yang, Sun
1993 Kobayashi, Rochat, Barrandon
1994 Rochat, Kobayashi, Barrandon
1993 Yang, Lavker, Sun
Upper human hair follicle contains a subpopulation of keratinocytes with superior in vitro proliferative potential. J Invest Dermatol. 1993;101:652-9 (
Fig. 18 [Fig.l] Different parts of a human anagen hair follicle. Follicles were microdissected and separated into epidermis (E), upper follicle (UF), lower follicle (LF), and bulb (B) as defined on the left. Abbreviations: Inf, infundibulum; SG, sebaceous gland; AM, arrector pili muscle; Is, isthmus; ORS, outer root sheath, FS, fibrous sheath; M, matrix; and DP, dermal papilla. Hematoxylin eosin-stained plastic section. Bar, 200
m. (Reproduced with permission.)
Comparison of the in-vitro growth potentials of different populations of human follicular cells reveals that keratinocytes of the upper follicle (isthmic mostly) grow better than those of the lower follicle, sebaceous gland, and epidermis. The authors conclude that follicular stem cells reside in the upper part of the follicle, most likely in the region of "the bulge."
Scalp follicles removed in toto and placed in culture showed outgrowths of keratinocytes, especially from below the sebaceous gland at a zone where the follicle widened. Upon examination by phase-contrast microscopy, the region was presumed to be "the bulge."
These studies do not permit the conclusion that stem cells are found mostly in "the bulge." In fact, "the bulge" constitutes only a small portion of the upper segment of a follicle, most of which consists of infundibulum and of isthmus apart from bulges. Superior growth potential in the upper segment of a follicle, therefore, does not necessarily implicate "the bulge" as the reservoir for stem cells. Furthermore, the techniques employed for "microdissecting" a follicle are crude and do not permit sharp segregation of isthmus from infundibulum and from stem. The researchers themselves, by their imprecise division of a follicle into upper follicle, lower follicle, and bulb, telegraph the message that they are unable to establish precise boundaries for a follicle even in a picture, let alone in microdissection of it. For example, in Figure 1 the infundibulum is not included in the "upper follicle" and the bulb is excluded from the "lower follicle."
Some of the names given in the photograph to parts of the follicle and its enveloping connective tissue are not correct.
1. The "dermal papilla" is really the follicular papilla.
2. The "upper follicle" really is the isthmus of the upper segment of the follicle.
3. The "lower follicle" is really the site of the lower segment of the follicle.
4. The "IS" lead line that points to the middle of the isthmus is misplaced because the inner sheath travels for only a very short distance beyond the attachment site of the M. erector pili, i.e., to the place where corneocytes of that sheath desquamate.
5. The lead line for "the bulge" goes to a site where the follicle is thinned; no "bulge" is apparent in the photomicrograph.
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