The importance of follicular stem cells in veterinary medicine in the context of skin tumours

Abstract

We read with special interest the article 'Canine hair-follicle keratinocytes enriched with bulge cells have the highly proliferative characteristic of stem cells' by Kobayashi et al. 1 published in Veterinary Dermatology. The study showed encouraging results, suggesting the existence of an epithelial stem cell compartment, based on immunohistochemistry, culture, microdissection and flow cytometry analysis.Currently, there is increasing interest in the follicular stem cell compartment, because this cell type is characterized by extensive growth and differentiation capacity, which may be applied to the development of new strategies in regenerative medicine and gene therapy. 2,3 Although occasionally forgotten, one of the applications of this new field of research resides in the better understanding of adnexal tumour differentiation and further elucidation of the histogenesis of a given tumour. 3 Despite interest in this approach, there are few studies describing the use of immunohistochemical markers to localize stem cell candidates in animal neoplasms. 1,2,4,5 Among these markers, CK15, CD34 and nestin are the only proteins that have been used in stem cell identification in veterinary medicine. 1,2,4,5 Immunolabelling for cytokeratin 15 (CK15) has been reported in sweat gland neoplasms, basal cell carcinomas, trichilemmomas and squamous cell carcinomas. [6][7][8] In contrast, pilomatricomas and Merkel cell carcinoma yielded negative results, [9][10][11] and in a clear cell adnexal carcinoma of a dog only 1% of neoplastic cells, which are supposed to have follicular origin, were positive for CK15. 12 The protein CD34, a hallmark of haematopoietic stem cells, recently demonstrated its value as a follicular stem cell marker in murine bulge keratinocytes. 13 The presence of mRNA and CD34 glycoprotein was demonstrated in the isthmic region of canine hair follicles by in situ hybridization and immunohistochemistry. 7 These findings support the hypothesis that dogs have a bulge-like region, similar to humans and mice. 5 Despite this, no studies regarding CD34 expression in cutaneous neoplasms from animals have been made to date.Finally, the neuroepithelial stem cell protein nestin, which was initially identified as a marker for neuronal progenitor cells, 3 was identified in the middle region of hair follicles in healthy dogs. 2 Nestin expression was variable in sweat gland tumours, 6 squamous cell carcinomas, 8 peritumoural stroma of basal cell carcinomas, trichoblastomas and trichoepitheliomas, 3 but was negative in Merkel cell carcinomas. 8 Expression patterns of other stem cell markers, such as B-lymphocyte-induced maturation protein-1, p63, CK19, CD200 and pleckstrin homology-like domain family A member 1, 3 need to be investigated in veterinary medicine, both in normal skin and in neoplastic skin disorders.

Equine Epidermis: A Source of Epithelial-Like Stem/Progenitor Cells with In Vitro and In Vivo Regenerative Capacities

“…Moreover, in the intact skin samples, both markers only coincided in areas where EpSCs were located: the epidermal basal cell layer, transition of dermal papilla, and bulge of the hair follicle. Indeed, the presence of stem cells has been previously reported in these areas [8,9].…”

“…On the other hand, ongoing regeneration of the skin is achieved through somatic stem cell differentiation within the epidermis and the hair follicle. The skin may, hence, serve as an excellent source of epithelial-like stem/progenitor cells (EpSCs) [8,9]. Accordingly, it has been proposed that EpSCs might be useful in the treatment of several diseases, such as burn wounds, chronic wounds, and ulcers [10].…”

Sphere-Forming Capacity as an Enrichment Strategy for Epithelial-Like Stem Cells from Equine Skin

“…In particular, it has been suggested as the main source of epithelial-like stem cells (EpSCs) [15,32]. Besides the presence of somatic stem cells in hair follicles and dermis, the epidermis also contains a compartment of stem cells [9,14] which are of different maturity levels.…”

Stem cell therapy in veterinary dermatology

“…In a letter to the editor of Veterinary Dermatology , Grandi et al. 53 noted that use of immunohistochemical markers found on bulge stem cells might help to elucidate the histogenesis of certain tumours. In particular, ceratokeratin (CK15), CD34 and nestin have been reported in the veterinary literature 6,50,54,55 .…”