Platelet sonicates activate hair follicle stem cells and mediate enhanced hair follicle regeneration

Abstract

An increasing number of studies show that platelet-rich plasma (PRP) is effective for androgenic alopecia (AGA). However, the underlying cellular and molecular mechanisms along with its effect on hair follicle stem cells are poorly understood. In this study, we designed to induce platelets in PRP to release factors by calcium chloride (PC) or by sonication where platelet lysates (PS) or the supernatants of platelet lysate (PSS) were used to evaluate their effect on the hair follicle activation and regeneration. We found that PSS and PS exhibited a superior effect in activating telogen hair follicles than PC. In addition, PSS injection into the skin activated quiescent hair follicles and induced K15 + hair follicle stem cell proliferation in K14-H2B-GFP mice.Moreover, PSS promoted skin-derived precursor (SKP) survival in vitro and enhanced hair follicle formation in vivo. In consistence, protein array analysis of different PRP preparations revealed that PSS contained higher levels of 16 growth factors (out of 41 factors analysed) than PC, many of them have been known to promote hair follicle regeneration. Thus, our data indicate that sonicated PRP promotes hair follicle stem cell activation and de novo hair follicle regeneration. K E Y W O R D Sandrogenic alopecia, hair follicle regeneration, hair follicle stem cells, platelet sonicate, platelet-rich plasma

PI3K/Akt signaling pathway is essential for de novo hair follicle regeneration

“…These molecules included growth factors, cytokines, and ECM molecules, and many of them potentially activated PI3K/ Akt pathway [18,19]. This is consistent with recent findings that platelets and mesenchymal stem cells (MSCs) promote wound healing and hair regrowth through paracrine factors, which potentially induce activation of PI3K/Akt pathway in effector cells [33][34][35][36]. Platelets are the first cell type to arrive at the site of tissue injury, where they play diverse roles through the release of various bioactive molecules [37].…”

“…These studies imply an effect of PRP on hair follicle stem cells, which are key effector cells for hair follicle growth. Indeed, in our recent study, we found that PRP, which contained various growth factors, activated quiescent hair follicle stem cells to proliferate, resulting in the transition of telogen (resting phase) to anagen (growing phase) hair follicles in mice [35]. In line with these observations, recent studies showed that transplantation of autologous cells prepared from the hair follicle could form de novo hair follicles in AGA patients [53,54].…”

“…Platelets are the first cell type to arrive at the site of tissue injury, where they play diverse roles through the release of various bioactive molecules [37]. A growing number of preclinical studies have shown that platelet-rich plasma (PRP), which contains a variety of growth factors [35], has multiple activities in enhancing injury repair of various tissues, such as the bone, tendon, ligament, and muscle [38,39]. As multipotent stem cells, MSCs can differentiate into cells in the bone, cartilage, and fat [40].…”

Platelet-rich plasma accelerates skin wound healing by promoting re-epithelialization

“…Damage to or the absence of skin appendages not only delays wound healing but also leads to incomplete skin function and scar outcomes [ 43 ]. There have been clinical cases of PRP used in the treatment of alopecia [ 44 , 45 ], and further in-depth research found that it could affect the hair growth cycle and is beneficial to hair follicle reconstruction [ 46 , 47 ]. Interestingly, the hair follicles and sebaceous glands were distributed in the newborn skin in the PRP group on day 14, which is consistent with previous research.…”

Thymosin β4 Identified by Transcriptomic Analysis from HF Anagen to Telogen Promotes Proliferation of SHF-DPCs in Albas Cashmere Goat

“…For adipose-derived research [44][45][46], the components that are typically used for aesthetic and dermal applications consist of nanofat, stromal vascular fraction cells (SVFs), adipose-derived mesenchymal stem cells (AD-MSCs), and extracellular vesicle (EVs), which have all shown capability to repair, regenerate, and rejuvenate surrounding tissue. For blood-derived research [47][48][49][50][51], studies focused on platelet-rich plasma (PRP), which is a whole-blood centrifuged concentrate that contains proteins and growth factors (GFs) but not red blood cells. However, although many papers on PRP have been published, the results are often contradictory.…”