Stem Cells in Keloid Lesions: A Review

Keloid disorder (KD) is a fibroproliferative condition associated with excessive dermal collagen deposition into the extracellular matrix (ECM), in response to wounding of the skin.1,2 In contrast to hypertrophic scars, keloid lesions (KLs) extend beyond the boundaries of the original wound and rarely regress. The most common sites of predilection for KLs are the anterior chest, shoulders, upper back, and earlobes.3 These lesions present as firm, shiny, rubbery lesions and are often associated with pruritus, pain, disfigurement, and joint contracture.4 Disfiguring KLs can lead to profound functional and psychological sequelae, impacting the patient’s quality of life.5,6 KLs can occur in individuals of any ethnicity but it is most prevalent in patients with darker skin pigmentation especially those of African descent with an incidence of 6%–16%.3,7 Conversely, KLs are extremely rare in albinos.8 KD affects men and women equally, with a peak age of onset of 10–30 years.3,9 Several studies investigating patients with a positive family history of KD suggest a predominantly autosomal dominant pattern of inheritance with incomplete penetrance in the predisposition.10,11 Additionally, human leukocyte antigens polymorphisms have been implicated in KD.12 Two genome-wide association studies have also isolated 4 single-nucleotide polymorphisms associated with KD.11,13,14 The mainstay treatment for KLs includes intralesional corticosteroid injections, either as a monotherapy or in combination with other treatment modalities15 including cryotherapy, 5-flurouracil, radiotherapy, laser therapy, surgical excision, or silicon occlusive dressing. Despite a plethora of treatment options, the outcome of the treatment is often unsatisfactory with recurrence rates of 45%–100%.16,17 Stem cells are cells that possess unlimited self-renewal capacity and the ability to give rise to daughter cells capable of undergoing differentiation into specialized differentiated cells.18,19 There is increasing evidence of the involvement of stem cells, the renin-angiotensin system (RAS), and the immune system, in the pathogenesis of KD.20,21 This review outlines the characteristic of the major cell populations within KLs, focuses on the role of stem cells and their potential roles in the generation of the aberrant fibroblasts and myofibroblasts, the RAS, and the immune system, in KD.