Hair loss, or alopecia, is associated with several psychosocial and medical comorbidities, and it remains an economic burden to individuals and the society. Alopecia is attributable to varied mechanisms and features a multifactorial predisposition, and the available conventional medical interventions have several limitations. Thus, several therapeutic strategies for alopecia in regenerative medicine are currently being explored, with increasing evidence suggesting that mesenchymal stem cell (MSC) implantation, MSC-derived secretome treatment, and blood-derived platelet-rich plasma therapies are potential treatment options. In this review, we searched the Cochrane Library, MEDLINE (PubMed), EMBASE, and Scopus using various combinations of terms, such as \"stem cell,\" \"alopecia,\" \"hair loss,\" \"Androgenetic alopecia,\" \"male-pattern hair loss,\" \"female-pattern hair loss,\" \"regenerative hair growth,\" \"cell therapy,\" \"mesenchymal stem cells,\" \"MSC-derived extracellular vesicles,\" \"MSC-derived exosomes,\" and \"platelet-rich plasma\" and summarized the most promising regenerative treatments for alopecia. Moreover, further opportunities of improving efficacy and innovative strategies for promoting clinical application were discussed.

Lichen planopilaris (LPP) and frontal fibrosing alopecia (FFA) are primary, lymphocytic cicatricial hair loss disorders. These model epithelial stem cell (SC) diseases are thought to result from a CD8+ T-cell‒dominated immune attack on the hair follicle (HF) SC niche (bulge) after the latter has lost its immune privilege (IP) for as yet unknown reasons. This induces both apoptosis and pathological epithelial‒mesenchymal transition in epithelial SCs, thus depletes the bulge, causes fibrosis, and ultimately abrogates the HFs\' capacity to regenerate. In this paper, we synthesize recent progress in LPP and FFA pathobiology research, integrate our limited current understanding of the roles that genetic, hormonal, environmental, and other factors may play, and define major open questions. We propose that LPP and FFA share a common initial pathobiology, which then bifurcates into two distinct clinical phenotypes, with macrophages possibly playing a key role in phenotype determination. As particularly promising translational research avenues toward direly needed progress in the management of these disfiguring, deeply distressful cicatricial alopecia variants, we advocate to focus on the development of bulge IP and epithelial SC protectants such as, for example, topically effective, HF‒penetrating and immunoinhibitory preparations that contain tacrolimus, peroxisome proliferator-activated receptor-γ, and/or CB1 agonists.

The diverse populations of tissue-resident and transitory T cells present in the skin share a common functional need to enter, traverse, and interact with their environment. These processes are largely dependent on the regulated expression of adhesion molecules, such as selectins and integrins, which mediate bidirectional interactions between immune cells and skin stroma. Dysregulation and engagement of adhesion pathways contribute to ectopic T-cell activity in tissues, leading to the initiation and/or exacerbation of chronic inflammation. In this paper, we review how the molecular interactions supported by adhesion pathways contribute to T-cell dynamics and function in the skin. A comprehensive understanding of the molecular mechanisms underpinning T-cell adhesion in inflammatory skin disorders will facilitate the development of novel tissue-specific therapeutic strategies.

An exploding public health crisis is the exponential growth in the incidence of chronic nonhealing ulcers associated with diseases such as diabetes. Various modalities have been developed to stimulate wound closure that is otherwise recalcitrant to standard clinical treatments. However, these approaches primarily focus on the process of re-epithelialization and are often deficient in regenerating the full spectrum of structures necessary for normal skin function. Autologous hair follicle grafting is a recent therapy to stimulate the closure of such nonhealing wounds, and we observed effects beyond the epidermis to other important components of the dermis. We found that hair follicle grafting facilitated the reappearance of various undifferentiated and differentiated layers of the epidermis with the restoration of epidermal junctions. In addition, other important structures that are critical for cutaneous health and function such as the blood and lymph vasculature, nerve fibers, and sweat gland structures were restored in postgrafted wounds. Interestingly, both immune cells and inflammatory signals were substantially decreased, indicating a reduction in the chronic inflammation that is a hallmark of nonhealing wounds. Our observation that punch wounds created on the postgrafted area likewise healed suggests that this is a self-sustaining long-term therapy for patients with chronic wounds.

DP (dermal papilla) is a mesenchyme-derived structure situated at the base of the HF (hair follicle) that plays an important role in embryonic hair morphogenesis and maintenance of the hair growth cycle. hMSCs (human mesenchymal stem cells) have gained widespread attention in the field of tissue engineering, but not much is known about the differentiation of hMSCs into DP cells. hMSCs involved in HF formation were examined in our previous study. Here, we have explored the differentiation potential of hMSCs into DP cells by co-culturing hMSCs with DP cells, which proved to be the case. During the differentiation process, the expression of versican, CD133, SCF (stem cell factor), ET-1 (endothelin-1) and bFGF (basic fibroblast growth factor) increased. Compared with hMSCs alone, the aggregate number clearly increased when co-cultured with DP cells. The expression in vivo of HLA-I (human leucocyte antigen class I) was confined to DP of the newly formed HF. The data suggest that hMSCs possess the potential to differentiate into DP cells in vivo and in vitro.