Human fibroblast‐derived extracellular vesicles promote hair growth in cultured human hair follicles

Abstract

Hair loss is a prevalent medical condition affecting both genders. In this study, we investigate the effects of a specific class of extracellular vesicles (EVs), namely human normal fibroblast‐derived EVs (hFB‐EVs), on human dermal papilla (DP) and outer root sheath (ORS) cells and examine the molecular mechanisms responsible for hair growth in hair follicles (HFs). We find that Wnt3a, which maintains the hair‐generating activity of DP cells, is enriched and more strongly associated with hFB‐EVs than with fibroblasts. Furthermore, hFB‐EV‐associated Wnt3a mediated receptor activation in cultured DP cells, leading to an increase in β‐catenin in the cytoplasm and its translocation into the nucleus, thereby elevating expression of the target genes Axin2 and Lef1. Additionally, hFB‐EVs promoted the migration, proliferation, and differentiation of ORS cells and elongation of the hair shaft in human HFs. These findings revealed a novel mechanism by which hFB‐EVs influence hair growth.

Application of Cell-Derived Extracellular Vesicles and Engineered Nanovesicles for Hair Growth: From Mechanisms to Therapeutics

“…In addition, treatment also increased the cell proliferation and migration and expression of keratin 6, 16, 17, and 75 in ORSCs. Finally, treatment of hFB-EVs increased the shaft elongation of human HFs ex vivo ( Rajendran et al, 2021b ).…”

“…Macrophage-derived EVs and EMs have both been shown to increase the levels of β-catenin, ALP, versican, and survival markers (pAKT, pERK, and Bcl-2) in DPCs ( Rajendran et al, 2020 ; Rajendran et al, 2021a ). Similarly, fibroblast-derived EVs carry Wnt3a or Norrin that activate the Wnt/β-catenin-relayed signaling pathways in DPCs ( Riche et al, 2019 ; Rajendran et al, 2021b ). In addition, fibroblast-derived EVs induced ORSC differentiation by increasing the transcriptional expression of keratins ( Rajendran et al, 2021b ), whereas activated fibroblast-derived EVs regulated the Norrin-encoding genes of DPCs ( Riche et al, 2019 ).…”

Extracellular Vesicles: Emerging Therapeutics in Cutaneous Lesions

“… 20 Furthermore, dermal fibroblasts and Dermal Papilla Cells (DPCs) have the capacity to enhance hair growth through EVs and this will be discussed in detail in the subsequent sections. 21 , 22 In addition to cutaneous lesions, skin cell-derived EVs can also be used to treat other diseases. For example, skin-derived precursor Schwann cells (SKP-SCs) have been reported to have a neuroprotective effect in the peripheral nervous system.…”

“… Promoted the migration, proliferation, and differentiation of ORS cells and elongation of the hair shaft in human HFs. [ 21 ] Macrophage Not specific DPC Enhanced the hair follicle growth associated with Wnt3a, Wnt7b, phosphorylated Akt and Bcl-2. In Balb/c mice, promoted HF growth and increased hair shaft size in a short period in human HFs.…”

Extracellular Vesicles Act as Nano-Transporters of Tyrosine Kinase Inhibitors to Revert Iodine Avidity in Thyroid Cancer

“…EVs are classified as exosomes, microvesicles, and apoptotic bodies based on their biogenesis and release pathways. EVs deliver proteins, lipids, miRNA, mRNA, and even DNA to recipient cells [5][6][7]. Hence, research scientists are concentrating on exploiting EVs as a drug delivery nano-transporter.…”