Eccrine Sweat Glands are Major Contributors to Reepithelialization of Human Wounds

Abstract

Eccrine sweat glands are skin-associated epithelial structures (appendages) that are unique to some primates including humans and are absent in the skin of most laboratory animals including rodents, rabbits, and pigs. On the basis of the known importance of other skin appendages (hair follicles, apocrine glands, and sebaceous glands) for wound repair in model animals, the present study was designed to assess the role of eccrine glands in the repair of wounded human skin. Partial-thickness wounds were generated on healthy human forearms, and epidermal repair was studied in skin biopsy samples obtained at precise times during the first week after wounding. Wound reepithelialization was assessed using immunohistochemistry and computer-assisted 3-dimensional reconstruction of in vivo wounded skin samples. Our data demonstrate a key role for eccrine sweat glands in reconstituting the epidermis after wounding in humans. More specifically, (i) eccrine sweat glands generate keratinocyte outgrowths that ultimately form new epidermis; (ii) eccrine sweat glands are the most abundant appendages in human skin, outnumbering hair follicles by a factor close to 3; and (iii) the rate of expansion of keratinocyte outgrowths from eccrine sweat glands parallels the rate of reepithelialization. This novel appreciation of the unique importance of eccrine sweat glands for epidermal repair may be exploited to improve our approaches to understanding and treating human wounds.

Reduced cell cohesiveness of outgrowths from eccrine sweat glands delays wound closure in elderly skin

“…Consecutive horizontally cut skin sections were immunostained for epithelial markers (pan‐keratin) and photographed, and the images were reassembled to create 3D reconstructions of skin, using computer software as described in Experimental Procedures. As previously reported (Rittié et al ., 2013), we observed that young human skin produces discernible keratinocyte outgrowths from both ESGs and pilo‐sebaceous units (PSUs, i.e., hair follicles and associated sebaceous glands), within 3 days following wounding (a representative pan‐keratin‐stained transverse section is shown in Fig. 1A).…”

“…Our prior studies showed that, under our experimental conditions, CO 2 laser treatment ablated the entire epidermis, the basement membrane, and the uppermost portion of the papillary dermis (Rittié et al ., 2011, 2013). Moreover, we showed that keratinocyte outgrowths from ESGs are major contributors to re‐epithelialization of partial‐thickness wounds in young adults.…”

“…1A). Epidermal repair occurs through expansion of keratinocyte outgrowths merging with each other until they cover the entire wounded area ((Rittié et al ., 2013) and Fig. 1; animated versions in Video S1).…”

“…We previously reported that partial‐thickness wounding of young human skin triggers a proliferative response in ESGs and PSUs underlying the wound (Rittié et al ., 2013). To assess whether reduced outgrowth from ESGs in aged skin stemmed from reduced proliferative response, we compared spatial distribution of proliferative cells within PSUs and ESGs in young and aged skins following wounding.…”

“…Wounds created by this procedure are highly reproducible and heal according to a typical repair process that can be readily studied (Orringer et al ., 2004; Rittié et al ., 2011, 2013). Using this method, we have shown that humans heal in a unique way, in that eccrine sweat glands (ESGs) play a major role in contributing new keratinocytes for epidermal repair, alongside less abundant hair follicles (Rittié et al ., 2013). …”