| 研究生: |
王彥淮 Wang, Yen-Huai |
|---|---|
| 論文名稱: |
以細胞模式篩選促毛髮生成之相關因子 In vitro screening for hair formation-related factors |
| 指導教授: |
黃玲惠
Huang, Lynn L.H. |
| 學位類別: |
碩士 Master |
| 系所名稱: |
生物科學與科技學院 - 生物科技與產業科學系 Department of Biotechnology and Bioindustry Sciences |
| 論文出版年: | 2019 |
| 畢業學年度: | 107 |
| 語文別: | 中文 |
| 論文頁數: | 78 |
| 中文關鍵詞: | 細胞交互作用 、毛囊再生 、細胞增生 、細胞移行 、生長因子 |
| 外文關鍵詞: | hair formation, cell proliferation, cell migration, growth factor |
| 相關次數: | 點閱:67 下載:0 |
| 分享至: |
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人類毛髮在外觀上扮演著極重要的角色。毛髮生長起始自毛囊發育,毛髮成熟後會進入周而復始的毛髮週期。其中,真皮細胞和表皮細胞之間的交互作用扮演毛髮生成之重要角色。在此發育過程中有許多不同的生長因子參與其中。過去實驗室探究HR1於毛髮再生的影響。於是,本研究欲進一步使用一個可以運用在毛囊再生實驗上的細胞模式,並以此作為篩選平台,探討可幫助毛髮生成中,細胞層次的影響。在這邊,本實驗將以細胞增生、移行做為細胞模式篩選平台,篩選出促毛髮生成之HR因子與適當濃度,再將有效的HR因子分別以100 ng/ml濃度方式組合成為雞尾酒混合組,觀察兩組配對、三組配對與四組配對是否有促進增生或移行的效果。真皮細胞實驗結果顯示,HR1、3、4可促進真皮細胞增生,且HR3有最顯著之效果,HR1、4可促進真皮細胞移行,且HR4有最顯著之效果。表皮細胞HaCaT實驗結果顯示,HR1、3、4、8可促進表皮細胞增生與移行,但於表皮細胞增生中均無較突出之組別,不過在表皮細胞移行中,凡是涉及HR3者均有較為顯著的效果。綜合上述,以此細胞模式篩選平台篩選對真皮、表皮細胞增生、移行有效之毛髮生成相關因子、濃度與混合組合可做為未來幫助毛髮生長研究。
During the beginning of hair development, hair follicles develop to hair fibers and go to hair cycle. Hair formation involved multiple factors and epidermal-dermal cell interaction. In our pilot study a member found HR(Hair Regeneration)1 can enhance hair formation, so here we used the in vitro platform on hair formation to screen other optimal HR factors at cell level. In our study, we added HR factors, which were some mitogens for hair formation, to test how they affected hair formation. We performed proliferation and migration assays for screening and found optimal concentrations for HR factors. After single HR factor screening, we use the concentration of 100 ng/ml for each HR factor, later combine different factors together to designate as the cocktail treatment groups, for the optimization of HR effect. In our results, we found HR1, 3, and 4 enhanced dermal cell proliferation and HR3 has the best effect. In the migration assay, both HR1 and HR4 enhanced dermal cell migration and HR4 had the best effect. Using HaCaT as the cell model for epidermal cell, we found HR1, 3, 4, and 8 had positive effect on proliferation, and HR1, 3, 4, and 8 also have positive effect on migration. In cocktail treatments, we found that several groups involved HR4 can enhance dermal cell migration. The groups involved HR3 can enhance HaCaT migration. According to this study, in vitro screening assay can be a good platform for searching benefit factor on hair formation, and HR factors can enhance proliferation or migration of dermal and epidermal cells under different situations. Last but not least, we can use this cell platform to screen the optimal hair formation-related factors and their optimal concentration beneficial for hair formation.
陳彥蓉,Wnt10b 及β-catenin 在毛囊發育的表現,國立成功大學生物科技研究所碩士論文,2014。
梁志豪,HR1因子對於毛囊再生的作用,國立成功大學生物科技研究所碩士論文,2016。
黃珮青,血小板生長因子之功能性分析,國立成功大學生物科技研究所碩士論文,2011。
蔡淯亘,Wnt蛋白質在小鼠毛髮不同發育階段的分布,國立成功大學生物科技研究所碩士論文,2012。
羅韻綺,以體外皮膚培養系統研究微環境對於毛囊之初始發育,國立成功大學生物科技研究所碩士論文,2009。
Ahtiainen, L., Lefebvre, S., Lindfors, P.H., Renvoise, E., Shirokova, V., Vartiainen, M.K., Thesleff, I., and Mikkola, M.L. Directional cell migration, but not proliferation, drives hair placode morphogenesis. Developmental Biology 28, 588-602, 2014.
Alonso, L., and Fuchs, E. The hair cycle. Journal of Cell Science 119, 391-393, 2006.
Baker, R.E., and Murray, P.J. Understanding hair follicle cycling: a systems approach. Current Opinion in Genetics and Development 22, 607-612, 2012.
Bhushan, B., Wei, G., and Haddad, P. Friction and wear studies of human hair and skin. Wear 259, 1012-1021, 2005.
Blume, U., Ferracin, J., Verschoore, M., Czernielewski, J.M., and Schaefer, H. Physiology of the vellus hair follicle: hair growth and sebum excretion. British Journal of Dermatology 124, 21-28, 1991.
Bonacich, E. A theory of ethnic antagonism: The split labor market. American Sociological Review, 547-559, 1972.
Botchkarev, V.A., and Paus, R. Molecular biology of hair morphogenesis: development and cycling. Journal of Experimental Zoology Part B Molecular and Developmental Evolution 298, 164-180, 2003.
Cheng, P., Gao, Z.Q., Liu, Y.H., and Xue, Y.X. Platelet-derived growth factor BB promotes the migration of bone marrow-derived mesenchymal stem cells towards C6 glioma and up-regulates the expression of intracellular adhesion molecule-1. Neuroscience Letters 451, 52-56, 2009.
Chiu, H.C., Chang, C.H., Chen, J.S., and Jee, S.H. Human hair follicle dermal papilla cell, dermal sheath cell and interstitial dermal fibroblast characteristics. Journal of the Formosan Medical Association 95, 667-674, 1996.
Commo, S., Gaillard, O., and Bernard, B.A. Human hair greying is linked to a specific depletion of hair follicle melanocytes affecting both the bulb and the outer root sheath. British Journal of Dermatology 150, 435-443, 2004.
Cotsarelis, G. Epithelial stem cells: a folliculocentric view. Journal of Investigative Dermatology 126, 1459-1468, 2006.
Couchman, J.R. Rat hair follicle dermal papillae have an extracellular matrix containing basement membrane components. Journal of Investigative Dermatology 87, 762-767, 1986.
Cutrone, M., and Grimalt, R. Transient neonatal hair loss: a common transient neonatal dermatosis. European Journal of Pediatrics 164, 630-632, 2005.
DasGupta, R., and Fuchs, E. Multiple roles for activated LEF/TCF transcription complexes during hair follicle development and differentiation. Development 126, 4557-4568, 1999.
Driskell, R.R., Clavel, C., Rendl, M., and Watt, F.M. Hair follicle dermal papilla cells at a glance. Journal of Cell Science 124, 1179-1182, 2011.
Ellis, J.A., Sinclair, R., and Harrap, S.B. Androgenetic alopecia: pathogenesis and potential for therapy. Expert Reviews in Molecular Medicine 4, 1-11, 2002.
Eun Kim, J., Ahn, B.C., Won Lee, H., Hwang, M.H., Hyun Shin, S., Woo Lee, S., Kwan Sung, Y., and Lee, J. In vivo monitoring of survival and proliferation of hair stem cells in a hair follicle generation animal model. Molecular Imaging 12, 310-317, 2013.
Franco, C.D. Connective tissues associated with peripheral nerves. Regional Anesthesia and Pain Medicine 37, 363-365, 2012.
Gat, U., DasGupta, R., Degenstein, L., and Fuchs, E. De Novo hair follicle morphogenesis and hair tumors in mice expressing a truncated beta-catenin in skin. Cell 95, 605-614, 1998.
Gensure, R.C. Parathyroid hormone-related peptide and the hair cycle - is it the agonists or the antagonists that cause hair growth? Experimental Dermatology 23, 865-867, 2014.
Gupta, A.K., and Charrette, A. The efficacy and safety of 5alpha-reductase inhibitors in androgenetic alopecia: a network meta-analysis and benefit-risk assessment of finasteride and dutasteride. Journal of Dermatological Treatment 25, 156-161, 2014.
Hadshiew, I.M., Foitzik, K., Arck, P.C., and Paus, R. Burden of hair loss: stress and the underestimated psychosocial impact of telogen effluvium and androgenetic alopecia. Journal of Investigative Dermatology 123, 455-457, 2004.
Hammel, H.T. Regulation of internal body temperature. Annual Review of Physiology 30, 641-710, 1968.
Hennessy, A., Oh, C., Diffey, B., Wakamatsu, K., Ito, S., and Rees, J. Eumelanin and pheomelanin concentrations in human epidermis before and after UVB irradiation. Pigment Cell Research 18, 220-223, 2005.
Iida, M., Ihara, S., and Matsuzaki, T. Hair cycle-dependent changes of alkaline phosphatase activity in the mesenchyme and epithelium in mouse vibrissal follicles. Development, Growth and Differentiation 49, 185-195, 2007.
Ito, M., Kizawa, K., Hamada, K., and Cotsarelis, G. Hair follicle stem cells in the lower bulge form the secondary germ, a biochemically distinct but functionally equivalent progenitor cell population, at the termination of catagen. Differentiation 72, 548-557, 2004.
Ivanov, V.N., and Ronai, Z. p38 protects human melanoma cells from UV-induced apoptosis through down-regulation of NF-kappaB activity and Fas expression. Oncogene 19, 3003-3012, 2000.
Jahoda, C., and Oliver, R.F. The growth of vibrissa dermal papilla cells in vitro. British Journal of Dermatology 105, 623-627, 1981.
Jing, J., Wu, X.J., Li, Y.L., Cai, S.Q., Zheng, M., and Lu, Z.F. Expression of decorin throughout the murine hair follicle cycle: hair cycle dependence and anagen phase prolongation. Experimental Dermatology 23, 486-491, 2014.
Kimura-Ueki, M., Oda, Y., Oki, J., Komi-Kuramochi, A., Honda, E., Asada, M., Suzuki, M., and Imamura, T. Hair cycle resting phase is regulated by cyclic epithelial FGF18 signaling. Journal of Investigative Dermatology 132, 1338-1345, 2012.
Klein, W.M., Wu, B.P., Zhao, S., Wu, H., Klein-Szanto, A.J., and Tahan, S.R. Increased expression of stem cell markers in malignant melanoma. Modern Pathology 20, 102-107, 2007.
Kligman, A.M. Pathologic dynamics of human hair loss. I. Telogen effuvium. Archives of Dermatology 83, 175-198, 1961.
Kollar, E.J. The induction of hair follicles by embryonic dermal papillae. Journal of Investigative Dermatology 55, 374-378, 1970.
Kopan, R., and Fuchs, E. A new look into an old problem: keratins as tools to investigate determination, morphogenesis, and differentiation in skin. Genes and Development 3, 1-15, 1989.
Lachgar, S., Charveron, M., Gall, Y., and Bonafe, J. Minoxidil upregulates the expression of vascular endothelial growth factor in human hair dermal papilla cells. The British Journal of Dermatology 138, 407-411, 1998.
Lademann, J., Richter, H., Meinke, M., Sterry, W., and Patzelt, A. Which skin model is the most appropriate for the investigation of topically applied substances into the hair follicles? Skin Pharmacology and Physiology 23, 47-52, 2010.
Lamoreux, M.L., Wakamatsu, K., and Ito, S. Interaction of major coat color gene functions in mice as studied by chemical analysis of eumelanin and pheomelanin. Pigment Cell Research 14, 23-31, 2001.
Lien, W.H., Polak, L., Lin, M., Lay, K., Zheng, D., and Fuchs, E. In vivo transcriptional governance of hair follicle stem cells by canonical Wnt regulators. Nature Cell Biology 16, 179-190, 2014.
Lim, J., and Thiery, J.P. Epithelial-mesenchymal transitions: insights from development. Development 139, 3471-3486, 2012.
Liu, S., Zhang, H., and Duan, E. Epidermal development in mammals: key regulators, signals from beneath, and stem cells. International Journal of Molecular Sciences 14, 10869-10895, 2013.
Mangelsdorf, S., Vergou, T., Sterry, W., Lademann, J., and Patzelt, A. Comparative study of hair follicle morphology in eight mammalian species and humans. Skin Research and Technology 20, 147-154, 2014.
McGill, G.G., Horstmann, M., Widlund, H.R., Du, J., Motyckova, G., Nishimura, E.K., Lin, Y.L., Ramaswamy, S., Avery, W., Ding, H.F., Jordan, S.A., Jackson, I.J., Korsmeyer, S.J., Golub, T.R., and Fisher, D.E. Bcl2 regulation by the melanocyte master regulator Mitf modulates lineage survival and melanoma cell viability. Cell 109, 707-718, 2002.
Morasso, M.I., and Tomic-Canic, M. Epidermal stem cells: the cradle of epidermal determination, differentiation and wound healing. Biology of the Cell 97, 173-183, 2005.
Nakamura, M., and Tokura, Y. Epithelial–mesenchymal transition in the skin. Journal of Dermatological Science 61, 7-13, 2011.
Nordvig, A.S., Owens, D.M., and Morris, R.J. CD133 in the selection of epidermal stem cells in mice: steps in the right direction. Journal of Investigative Dermatology 132, 2492-2494, 2012.
Ohyama, M., and Veraitch, O. Strategies to enhance epithelial-mesenchymal interactions for human hair follicle bioengineering. Journal of Dermatological Science 70, 78-87, 2013.
Ohyama, M., Zheng, Y., Paus, R., and Stenn, K.S. The mesenchymal component of hair follicle neogenesis: background, methods and molecular characterization. Experimental Dermatology 19, 89-99, 2010.
Oliveira, T., Dourado, L., Alves, L.D., Silva, I.M.B.M., Mendonca, L.S., Queiroz, L.F., Avila, M.P., and Gabriel, L.A.R. A new form of syndromic cone dystrophy: First case report of a 21 year old female with cone dystrophy associated with short anagen hair syndrome. Investigative Ophthalmology and Visual Science 55, 3278-3278, 2014.
Olsen, E.A., and Weiner, M.S. Topical minoxidil in male pattern baldness: effects of discontinuation of treatment. Journal of the American Academy of Dermatology 17, 97-101, 1987.
Olsen, E.A., Whiting, D.A., Savin, R., Rodgers, A., Johnson-Levonas, A.O., Round, E., Rotonda, J., Kaufman, K.D., and Male Pattern Hair Loss Study, G. Global photographic assessment of men aged 18 to 60 years with male pattern hair loss receiving finasteride 1 mg or placebo. Journal of the American Academy of Dermatology 67, 379-386, 2012.
Ouji, Y., Yoshikawa, M., Shiroi, A., and Ishizaka, S. Wnt-10b promotes differentiation of skin epithelial cells in vitro. Biochemical and Biophysical Research Communications 342, 28-35, 2006.
Pal, H.C., Baxter, R.D., Hunt, K.M., Agarwal, J., Elmets, C.A., Athar, M., and Afaq, F. Fisetin, a phytochemical, potentiates sorafenib-induced apoptosis and abrogates tumor growth in athymic nude mice implanted with BRAF-mutated melanoma cells. Oncotarget 6, 28296-28311, 2015.
Park, P.J., Moon, B.S., Lee, S.H., Kim, S.N., Kim, A.R., Kim, H.J., Park, W.S., Choi, K.Y., Cho, E.G., and Lee, T.R. Hair growth-promoting effect of Aconiti Ciliare Tuber extract mediated by the activation of Wnt/beta-catenin signaling. Life Sciences 91, 935-943, 2012.
Patzelt, A., Knorr, F., Blume-Peytavi, U., Sterry, W., and Lademann, J. Hair follicles, their disorders and their opportunities. Drug Discovery Today: Disease Mechanisms 5, e173-e181, 2008.
Pilcher, B.K., Dumin, J.A., Sudbeck, B.D., Krane, S.M., Welgus, H.G., and Parks, W.C. The activity of collagenase-1 is required for keratinocyte migration on a type I collagen matrix. The Journal of Cell Biology 137, 1445-1457, 1997.
Plikus, M.V., Vollmers, C., de la Cruz, D., Chaix, A., Ramos, R., Panda, S., and Chuong, C.M. Local circadian clock gates cell cycle progression of transient amplifying cells during regenerative hair cycling. Proceedings of the National Academy of Sciences of the United States of America 110, E2106-E2115, 2013.
Plog, S., Mundhenk, L., Langbein, L., and Gruber, A.D. Synthesis of porcine pCLCA2 protein during late differentiation of keratinocytes of epidermis and hair follicle inner root sheath. Cell and Tissue Research 350, 445-453, 2012.
Reddy, S., Andl, T., Bagasra, A., Lu, M.M., Epstein, D.J., Morrisey, E.E., and Millar, S.E. Characterization of Wnt gene expression in developing and postnatal hair follicles and identification of Wnt5a as a target of Sonic hedgehog in hair follicle morphogenesis. Mechanisms of Development 107, 69-82, 2001.
Rho, K.S., Jeong, L., Lee, G., Seo, B.M., Park, Y.J., Hong, S.D., Roh, S., Cho, J.J., Park, W.H., and Min, B.M. Electrospinning of collagen nanofibers: effects on the behavior of normal human keratinocytes and early-stage wound healing. Biomaterials 27, 1452-1461, 2006.
Robinson, S.J., and Healy, E. Human melanocortin 1 receptor (MC1R) gene variants alter melanoma cell growth and adhesion to extracellular matrix. Oncogene 21, 8037-8046, 2002.
Schmidt-Ullrich, R., and Paus, R. Molecular principles of hair follicle induction and morphogenesis. Bioessays 27, 247-261, 2005.
Schneider, M.R., Schmidt-Ullrich, R., and Paus, R. The hair follicle as a dynamic miniorgan. Current Biology 19, R132-R142, 2009.
Song, W.C., Hwang, W.J., Shin, C., and Koh, K.S. A new model for the morphology of the arrector pili muscle in the follicular unit based on three-dimensional reconstruction. Journal of Anatomy 208, 643-648, 2006.
Stenn, K., Parimoo, S., Zheng, Y., Barrows, T., Boucher, M., and Washenik, K. Bioengineering the hair follicle. Organogenesis 3, 6-13, 2007.
Stenn, K., and Paus, R. Controls of hair follicle cycling. Physiological Reviews 81, 449-494, 2001.
Tallarida, R.J. Drug synergism: its detection and applications. Journal of Pharmacology and Experimental Therapeutics 298, 865-872, 2001.
Tobin, D.J., and Bystryn, J.C. Different populations of melanocytes are present in hair follicles and epidermis. Pigment Cell Research 9, 304-310, 1996.
Trempus, C.S., Morris, R.J., Bortner, C.D., Cotsarelis, G., Faircloth, R.S., Reece, J.M., and Tennant, R.W. Enrichment for living murine keratinocytes from the hair follicle bulge with the cell surface marker CD34. Journal of Investigative Dermatology 120, 501-511, 2003.
Vogt, A., Hadam, S., Heiderhoff, M., Audring, H., Lademann, J., Sterry, W., and Blume-Peytavi, U. Morphometry of human terminal and vellus hair follicles. Experimental Dermatology 16, 946-950, 2007.
Wheeler, P.E. The evolution of bipedality and loss of functional body hair in hominids. Journal of Human Evolution 13, 91-98, 1984.
Whiting, D.A. Structural abnormalities of the hair shaft. Journal of the American Academy of Dermatology 16, 1-25, 1987.
Widelitz, R.B., Jiang, T.X., Lu, J., and Chuong, C.M. beta-catenin in epithelial morphogenesis: conversion of part of avian foot scales into feather buds with a mutated beta-catenin. Developmental Biology 219, 98-114, 2000.
Xia, L., Liu, Q., Zhang, W., Zhou, G., Cao, Y., and Liu, W. Enhanced proliferation and functions of in vitro expanded human hair follicle outer root sheath cells by low oxygen tension culture. Tissue Engineering Part C: Methods 18, 603-613, 2012.
Xing, Y.Z., Wang, R.M., Yang, K., Guo, H.Y., Deng, F., Li, Y.H., Ye, J.X., He, L., Lian, X.H., and Yang, T. Adenovirus-mediated Wnt5a expression inhibits the telogen-to-anagen transition of hair follicles in mice. International Journal of Medical Sciences 10, 908-914, 2013.
Yan, L., Cao, R., Wang, L., Liu, Y., Pan, B., Yin, Y., Lv, X., Zhuang, Q., Sun, X., and Xiao, R. Epithelial-mesenchymal transition in keloid tissues and TGF-beta1-induced hair follicle outer root sheath keratinocytes. Wound Repair and Regeneration 23, 601-610, 2015.
Yang, C.-C., and Cotsarelis, G. Review of hair follicle dermal cells. Journal of Dermatological Science 57, 2-11, 2010.
Yang, C.C., Sheu, H.M., Chung, P.L., Chang, C.H., Tsai, Y.S., Hughes, M.W., Tuan, T.L., and Huang, L.L. Leptin of dermal adipose tissue is differentially expressed during the hair cycle and contributes to adipocyte-mediated growth inhibition of anagen-phase vibrissa hair. Experimental Dermatology 24, 57-60, 2015.
Yim, E., Nole, K.L.B., and Tosti, A. 5α-Reductase inhibitors in androgenetic alopecia. Current Opinion in Endocrinology, Diabetes and Obesity 21, 493-498, 2014.
Zabierowski, S.E., and Herlyn, M. Melanoma stem cells: the dark seed of melanoma. Journal of Clinical Oncology 26, 2890-2894, 2008.
Zanoni, T.B., Tiago, M., Faião-Flores, F., de Moraes Barros, S.B., Bast, A., Hageman, G., de Oliveira, D.P., and Maria-Engler, S.S. Basic Red 51, a permitted semi-permanent hair dye, is cytotoxic to human skin cells: Studies in monolayer and 3D skin model using human keratinocytes (HaCaT). Toxicology Letters 227, 139-149, 2014.
Zhang, P., Ravuri, S.K., Wang, J., Marra, K.G., Kling, R.E., and Chai, J. Exogenous connective tissue growth factor preserves the hair-inductive ability of human dermal papilla cells. International Journal of Cosmetic Science 36, 442-450, 2014.
Zheng, Y., Du, X., Wang, W., Boucher, M., Parimoo, S., and Stenn, K.S. Organogenesis from dissociated cells: generation of mature cycling hair follicles from skin-derived cells. Journal of Investigative Dermatology 124, 867-876, 2005.