Regenerative medicine strategies for hair growth and regeneration: A narrative review of literature

Abstract

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.

Keywords: AA, alopecia areata; AA-PRP, autologous activated PRP; AD-MSCs, adipose tissue derived mesenchymal stromal cells; ADRCs, adipose-derived regenerative cells; ADSVCs, adipose-derived stromal vascular cells; AE, anagen effluvium; AGA, androgenetic alopecia; Alopecia; BM-MSCs, bone marrow derived mesenchymal stromal cells; CA, cicatricial alopecia; CD, cluster of differentiation; CM, conditioned medium; DHT, dihydrotestosterone; ECM, extracellular matrix; EGF, epidermal growth factor; EMA, European Medicines Agency; EMI, epithelial–mesenchymal interaction; EVs, extracellular vesicles; FDA, United States Food and Drug Administration; FGF, fibroblast growth factor; FPHL, female-pattern hair loss; GMP, good manufacturing practice; GVHD, graft-versus-host disease; HF, hair follicle; HFSCs, hair follicle stem cells; Hair follicle regeneration; Hair loss; Hair regrowth; IGF, insulin-like growth factor; IL, interleukin; ISSCR, The International Society for Stem Cell Research; KGF, keratinocyte growth factor; LA, lipedematous alopecia; LS, lipedematous scalp; MAPK/ERK, mitogen-activated protein kinases or extracellular signal-regulated kinases; MCP1, monocyte chemoattractant protein 1; MMP, matrix metalloproteinase; MPHL, male-pattern hair loss; MSCs, mesenchymal stromal cells; OS, oxidative stress; PDGF, platelet-derived growth factor; PG, prostaglandin; PI3K/Akt, phosphatidylinositol 3-kinase/protein kinase B; PMD-Act, pharmaceuticals and Medical Devices Agency-Act; PRP, platelet-rich plasma; ROS, reactive oxygen species; SALT, severity of alopecia tool; SCs, stem cells; SLE, systemic lupus erythematosus; SVF, stromal vascular fraction; Stem cell extracellular vesicles; Stem cell therapy; TA, traction alopecia; TE, telogen effluvium; TGF-β, transforming growth factor β; TNF, tumor necrosis factor; TTM, trichotillomania; Th, T helper; Treg, regulatory T cells; VEGF, vascular endothelial growth factor; Wnt, wingless/integrated-1; hDPCs, human dermal papilla cells; hUC-MSCs, umbilical cord blood-derived mesenchymal stromal cells; iPSC-MSCs, induced pluripotent stem cells derived mesenchymal stem cells; iPSCs, induced pluripotent stem cells; non-CA, non-cicatricial alopecia.