One of the emerging strategies for hair regeneration is to recover or replenish the signals responsible for hair development by the use of stem cells. Out of many, the following two strategies using stem cells hold the strongest prospects:
1. Conditioned Medium derived from stem cell culture
Recently, “Conditioned Medium”, the nutrient medium containing the abundant stem cell secretome has emerged as a possible therapeutic solution for hair regeneration [1]. Stem cell-derived CM is rich in a number of paracrine factors that can be explored as hair regenerative medicine. The factors that are secreted by stem cell and that can be found in CM are vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF), hepatocyte growth factor (HGF), platelet-derived growth factor (PDGF), bone morphogenic proteins (BMP), interleukin-6 (IL-6), macrophage colony-stimulating factor (M-CSF) and other cytokines that have been reported to be associated with hair regeneration via a variety of mechanisms[2]. VEGF, for instance, speeds up hair regeneration and augments the size of Hair Follicles and hair shafts by inducing perifollicular vascularization [3]. Dermal papilla cells (DPCs) are activated by both IGF -1/ IGF-1 binding protein-1 [4] complex and BMPs [5]. HGF, on the other hand, is a paracrine hormone that promotes follicular growth most probably by increasing the expression of B-catenin, a major player in different signalling pathways [6]. Additionally, IL-6 and M-CSF are found to play a role in hair wound-induced hair regrowth [7]. A large number of experimental studies have focused on modulating the composition and up-regulating the secretome of the stem cells, hence enhancing its therapeutic functions.
2. Stem-cell derived exosomes as vehicles of hair regenerating signals
Exosomes are a sub-group of extracellular vesicles of 40-120um in size that are used as a transportation medium for cellular cargo from cell to cell [8]. Exosomes are carriers of all sorts of molecules like RNA, DNA and proteins. It has been reported that hydrophobic surface proteins on the exosomes, namely Wnt, was found to induce B-catenin activation over a distance, which is a critical signalling pathway in the regulation of hair morphogenesis and regeneration [9]. Mesenchymal stem cell-derived exosomes are one of the best candidates that have shown promise when it comes to hair regrowth, as shown by a patented experimental observation [10]. Since exosomes are involved in paracrine signalling, it is now evident that regulatory functions of DPCs in hair follicle regeneration can be exploited by DPCs derived exosomal vehicles [11].
References:
1. Kim, H.O., Choi, S.M., Kim, H.S., 2013. Mesenchymal stem cell-derived secretome and microvesicles as cell-free therapeutics for neurodegenerative disorders.
2. Kruglikov, I.L., Scherer, P.E., 2016. Dermal adipocytes and hair cycling: Is spatial heterogeneity a characteristic feature of the dermal adipose tissue depot? Exp. Dermatol. 25, 258–262 https://doi.org/10.1111/exd.12941
3. Yano, K., Brown, L.F., Detmar, M., 2001. Control of hair growth and follicle size by VEGF-mediated angiogenesis. J. Clin. Invest. 107, 409–417. https://doi.org/10.1172/JCI11317
4. Bak, D.H., Choi, M.J., Kim, S.R., Lee, B.C., Kim, J.M., Jeon, E.S., Oh, W., Lim, E.S., Park, B.C., Kim, M.J., Na, J., Kim, B.J., 2018. Human umbilical cord blood mesenchymal stem cells engineered to overexpress growth factors accelerate outcomes in hair growth. Korean J. Physiol. Pharmacol. 22, 555–566. 471 https://doi.org/10.4196/kjpp.2018.22.5.555
5. Rendl, M., Polak, L., Fuchs, E., 2008. BMP signaling in dermal papilla cells is required for their hair follicle-inductive properties. Genes Dev. 22, 543–557. https://doi.org/10.1101/gad.1614408
6. Qi, Y., Li, M., Xu, L., Chang, Z., Shu, X., Zhou, L., 2016. Therapeutic role of human hepatocyte growth factor (HGF) in treating hair loss. PeerJ 4, e2624. https://doi.org/10.7717/peerj.2624
7. Talavera-Adame, D., Newman, D., Newman, N., 2017. Conventional and novel stem cell based therapies for androgenic alopecia. Stem Cells Cloning Adv. Appl. 10, 11–19. https://doi.org/10.2147/SCCAA.S138150
8. Jiang, X.C., Gao, J.Q., 2017. Exosomes as novel bio-carriers for gene and drug 640 delivery. Int. J. Pharm., 167–175. https://doi.org/10.1016/j.ijpharm.2017.02.038
9. Dey-Rao, R., Sinha, A.A., 2017. A genomic approach to susceptibility and pathogenesis leads to identifying potential novel therapeutic targets in 531 androgenetic alopecia. Genomics 109, 165–176. https://doi.org/10.1016/j.ygeno.2017.02.005
10. Levi, S.K.L., Yeo, M.S.W., Chen, T.S., Lai, R.C., 2013. Use of exosomes to promote or enhance hair growth. US20130209528A1
11. Zhou, L., Wang, H., Jing, J., Yu, L., Wu, X., Lu, Z., 2018. Regulation of hair follicle 915 development by exosomes derived from dermal papilla cells. Biochem. Biophys. 916 Res. Commun. 500, 325–332. https://doi.org/10.1016/j.bbrc.2018.04.067
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