Research progress of hair follicle and related stem cells in scar-free wound healing_Chinese Journal of Reparative and Reconstructive Surgery

Authors：

ZHOU Zhentao ¹ , ZHAO Qinyuan ² , ZHAO Jun ³ ,  ZHANG Jufang ²

1. The Fourth Clinical College of Zhejiang Chinese Medicine University, Hangzhou Zhejiang, 310013, P.R.China;
2. Department of Plastic Surgery, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou Zhejiang, 310006, P.R.China;
3. Nanjing Medical University, Nanjing Jiangsu, 211100, P.R.China;

Corresponding author：

ZHANG Jufang, Email: zhjuf@vip.sina.com

Keywords：

Hair follicle; hair follicle stem cells; dermal papilla cells; dermal sheath cells; wound healing; scarring

DOI：

10.7507/1002-1892.202005086

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

Objective To explore the research progress of hair follicle and related stem cells in scar-free skin healing in recent years.Methods The literature related to hair follicle and related stem cells, wound healing, and scar formation in recent years was extensively reviewed and summarized from the aspects of cell function and molecular mechanism.Results Scar tissue after wound healing treated with hair follicle transplantation and related stem cell therapy is more mild or even without scar formation. The cell types and molecular mechanisms of the above phenomena are complex, and the bone morphogenetic protein signal transduction pathway and Wnt signal transduction pathway are strongly correlated.Conclusion The research of hair follicle and related stem cells in scar-free skin healing is at the initial stage at present. Strengthening the mechanism research may provide new ideas for the treatment of wound and scar.

Citation： ZHOU Zhentao, ZHAO Qinyuan, ZHAO Jun, ZHANG Jufang. Research progress of hair follicle and related stem cells in scar-free wound healing. Chinese Journal of Reparative and Reconstructive Surgery, 2021, 35(2): 241-245. doi: 10.7507/1002-1892.202005086 Copy

1.	Alam M, Cooley J, Plotczyk M, et al. Distinct patterns of hair graft survival after transplantation into 2 nonhealing ulcers: Is location everything? Dermatol Surg, 2019, 45(4): 557-565.
2.	Plikus MV, Guerrero-Juarez CF, Ito M, et al. Regeneration of fat cells from myofibroblasts during wound healing. Science, 2017, 355(6326): 748-752.
3.	Lim CH, Sun Q, Ratti K, et al. Hedgehog stimulates hair follicle neogenesis by creating inductive dermis during murine skin wound healing. Nat Commun, 2018, 9(1): 4903.
4.	Bernard BA. The hair follicle enigma. Exp Dermatol, 2017, 26(6): 472-477.
5.	张菊芳. 现代毛发移植技术. 杭州: 浙江科学技术出版社, 2018: 8.
6.	Paus R, Cotsarelis G. The biology of hair follicles. N Engl J Med, 1999, 341(7): 491-497.
7.	Taylor G, Lehrer MS, Jensen PJ, et al. Involvement of follicular stem cells in forming not only the follicle but also the epidermis. Cell, 2000, 102(4): 451-461.
8.	Janis JE, Harrison B. Wound healing: partⅠ. Basic science. Plast Reconstr Surg, 2014, 133(2): 199e-207e.
9.	Berman B, Maderal A, Raphael B. Keloids and hypertrophic scars: pathophysiology, classification, and treatment. Dermatol Surg, 2017, 43(Suppl 1): S3-S18.
10.	Pakshir P, Hinz B. The big five in fibrosis: Macrophages, myofibroblasts, matrix, mechanics, and miscommunication. Matrix Biol, 2018, 68-69: 81-93.
11.	Eming SA, Wynn TA, Martin P. Inflammation and metabolism in tissue repair and regeneration. Science, 2017, 356(6342): 1026-1030.
12.	Chen Z, Wang Z, Jin T, et al. Fibrogenic fibroblast-selective near-infrared phototherapy to control scarring. Theranostics, 2019, 9(23): 6797-6808.
13.	Martínez ML, Escario E, Poblet E, et al. Hair follicle-containing punch grafts accelerate chronic ulcer healing: A randomized controlled trial. J Am Acad Dermatol, 2016, 75(5): 1007-1014.
14.	杨震. 毛囊单位移植对创面修复的作用及创面愈合质量的研究. 上海: 复旦大学, 2009.
15.	Yang Z, Liu J, Zhu N, et al. Comparison between hair follicles and split-thickness skin grafts in cutaneous wound repair. Int J Clin Exp Med, 2015, 8(9): 15822-15827.
16.	刘家祺, 何安琪, 杨燕文, 等. 毛囊单位移植在皮肤创面修复中的应用. 中国美容医学, 2018, 27(2): 15-18.
17.	Narushima M, Mihara M, Yamamoto Y, et al. Hair transplantation for reconstruction of scalp defects using artificial dermis. Dermatol Surg, 2011, 37(9): 1348-1350.
18.	Willyard C. Unlocking the secrets of scar-free skin healing. Nature, 2018, 563(7732): S86-S88.
19.	Dituri F, Mancarella S, Cigliano A, et al. TGF-β as multifaceted orchestrator in HCC progression: signaling, EMT, immune microenvironment, and novel therapeutic perspectives. Semin Liver Dis, 2019, 39(1): 53-69.
20.	Ito M, Yang Z, Andl T, et al. Wnt-dependent de novo hair follicle regeneration in adult mouse skin after wounding. Nature, 2007, 447(7142): 316-320.
21.	Li B, Hu W, Ma K, et al. Are hair follicle stem cells promising candidates for wound healing? Expert Opin Biol Ther, 2019, 19(2): 119-128.
22.	Mathur AN, Zirak B, Boothby IC, et al. Treg-cell control of a CXCL5-IL-17 inflammatory axis promotes hair-follicle-stem-cell differentiation during skin-barrier repair. Immunity, 2019, 50(3): 655-667.
23.	Jensen KB, Collins CA, Nascimento E, et al. Lrig1 expression defines a distinct multipotent stem cell population in mammalian epidermis. Cell Stem Cell, 2009, 4(5): 427-439.
24.	Wang X, Chen H, Tian R, et al. Macrophages induce AKT/β-catenin-dependent Lgr5⁺ stem cell activation and hair follicle regeneration through TNF. Nat Commun, 2017, 8: 14091.
25.	Snippert HJ, Haegebarth A, Kasper M, et al. Lgr6 marks stem cells in the hair follicle that generate all cell lineages of the skin. Science, 2010, 327(5971): 1385-1389.
26.	Heidari F, Yari A, Rasoolijazi H, et al. Bulge hair follicle stem cells accelerate cutaneous wound healing in rats. Wounds, 2016, 28(4): 132-141.
27.	Quan R, Du W, Zheng X, et al. VEGF165 induces differentiation of hair follicle stem cells into endothelial cells and plays a role in in vivo angiogenesis. J Cell Mol Med, 2017, 21(8): 1593-1604.
28.	Du KT, Deng JQ, He XG, et al. MiR-214 regulates the human hair follicle stem cell proliferation and differentiation by targeting EZH2 and Wnt/β-catenin signaling way in vitro. Tissue Eng Regen Med, 2018, 15(3): 341-350.
29.	Choi YS, Zhang Y, Xu M, et al. Distinct functions for Wnt/β-catenin in hair follicle stem cell proliferation and survival and interfollicular epidermal homeostasis. Cell Stem Cell, 2013, 13(6): 720-733.
30.	Wei J, Melichian D, Komura K, et al. Canonical Wnt signaling induces skin fibrosis and subcutaneous lipoatrophy: a novel mouse model for scleroderma? Arthritis Rheum, 2011, 63(6): 1707-1717.
31.	Cheon SS, Cheah AY, Turley S, et al. beta-Catenin stabilization dysregulates mesenchymal cell proliferation, motility, and invasiveness and causes aggressive fibromatosis and hyperplastic cutaneous wounds. Proc Natl Acad Sci U S A, 2002, 99(10): 6973-6978.
32.	Bastakoty D, Saraswati S, Cates J, et al. Inhibition of Wnt/β-catenin pathway promotes regenerative repair of cutaneous and cartilage injury. FASEB J, 2015, 29(12): 4881-4892.
33.	Qiu W, Lei M, Li J, et al. Activated hair follicle stem cells and Wnt/β-catenin signaling involve in pathnogenesis of sebaceous neoplasms. Int J Med Sci, 2014, 11(10): 1022-1028.
34.	Sato M. Upregulation of the Wnt/beta-catenin pathway induced by transforming growth factor-beta in hypertrophic scars and keloids. Acta Derm Venereol, 2006, 86(4): 300-307.
35.	Madaan A, Verma R, Singh AT, et al. Review of hair follicle dermal papilla cells as in vitro screening model for hair growth. Int J Cosmet Sci, 2018, 40(5): 429-450.
36.	Rippa AL, Kalabusheva EP, Vorotelyak EA. Regeneration of dermis: scarring and cells involved. Cells, 2019, 8(6): 607.
37.	Qi SH, Liu P, Xie JL, et al. Experimental study on repairing of nude mice skin defects with composite skin consisting of xenogeneic dermis and epidermal stem cells and hair follicle dermal papilla cells. Burns, 2008, 34(3): 385-392.
38.	Leirós GJ, Kusinsky AG, Drago H, et al. Dermal papilla cells improve the wound healing process and generate hair bud-like structures in grafted skin substitutes using hair follicle stem cells. Stem Cells Transl Med, 2014, 3(10): 1209-1219.
39.	Yoshida Y, Soma T, Kishimoto J. Characterization of human dermal sheath cells reveals CD36-expressing perivascular cells associated with capillary blood vessel formation in hair follicles. Biochem Biophys Res Commun, 2019, 516(3): 945-950.
40.	Ma D, Kua JE, Lim WK, et al. In vitro characterization of human hair follicle dermal sheath mesenchymal stromal cells and their potential in enhancing diabetic wound healing. Cytotherapy, 2015, 17(8): 1036-1051.
41.	Tao Y, Yang Q, Wang L, et al. β-catenin activation in hair follicle dermal stem cells induces ectopic hair outgrowth and skin fibrosis. J Mol Cell Biol, 2019, 11(1): 26-38.
42.	李幼忱, 刘杰, 王德文, 等. 毛囊真皮鞘细胞在皮肤创伤愈合中作用的实验研究. 军事医学科学院院刊, 2009, 33(2): 144-147.
43.	Higgins CA, Roger MF, Hill RP, et al. Multifaceted role of hair follicle dermal cells in bioengineered skins. Br J Dermatol, 2017, 176(5): 1259-1269.
44.	Kaur P. Hair-follicle dermal papilla and sheath fibroblasts provide a supportive microenvironment for human skin regeneration. Br J Dermatol, 2017, 176(5): 1123-1124.
45.	Reynolds AJ, Lawrence C, Cserhalmi-Friedman PB, et al. Trans-gender induction of hair follicles. Nature, 1999, 402(6757): 33-34.

1. Alam M, Cooley J, Plotczyk M, et al. Distinct patterns of hair graft survival after transplantation into 2 nonhealing ulcers: Is location everything? Dermatol Surg, 2019, 45(4): 557-565.
2. Plikus MV, Guerrero-Juarez CF, Ito M, et al. Regeneration of fat cells from myofibroblasts during wound healing. Science, 2017, 355(6326): 748-752.
3. Lim CH, Sun Q, Ratti K, et al. Hedgehog stimulates hair follicle neogenesis by creating inductive dermis during murine skin wound healing. Nat Commun, 2018, 9(1): 4903.
4. Bernard BA. The hair follicle enigma. Exp Dermatol, 2017, 26(6): 472-477.
5. 张菊芳. 现代毛发移植技术. 杭州: 浙江科学技术出版社, 2018: 8.
6. Paus R, Cotsarelis G. The biology of hair follicles. N Engl J Med, 1999, 341(7): 491-497.
7. Taylor G, Lehrer MS, Jensen PJ, et al. Involvement of follicular stem cells in forming not only the follicle but also the epidermis. Cell, 2000, 102(4): 451-461.
8. Janis JE, Harrison B. Wound healing: partⅠ. Basic science. Plast Reconstr Surg, 2014, 133(2): 199e-207e.
9. Berman B, Maderal A, Raphael B. Keloids and hypertrophic scars: pathophysiology, classification, and treatment. Dermatol Surg, 2017, 43(Suppl 1): S3-S18.
10. Pakshir P, Hinz B. The big five in fibrosis: Macrophages, myofibroblasts, matrix, mechanics, and miscommunication. Matrix Biol, 2018, 68-69: 81-93.
11. Eming SA, Wynn TA, Martin P. Inflammation and metabolism in tissue repair and regeneration. Science, 2017, 356(6342): 1026-1030.
12. Chen Z, Wang Z, Jin T, et al. Fibrogenic fibroblast-selective near-infrared phototherapy to control scarring. Theranostics, 2019, 9(23): 6797-6808.
13. Martínez ML, Escario E, Poblet E, et al. Hair follicle-containing punch grafts accelerate chronic ulcer healing: A randomized controlled trial. J Am Acad Dermatol, 2016, 75(5): 1007-1014.
14. 杨震. 毛囊单位移植对创面修复的作用及创面愈合质量的研究. 上海: 复旦大学, 2009.
15. Yang Z, Liu J, Zhu N, et al. Comparison between hair follicles and split-thickness skin grafts in cutaneous wound repair. Int J Clin Exp Med, 2015, 8(9): 15822-15827.
16. 刘家祺, 何安琪, 杨燕文, 等. 毛囊单位移植在皮肤创面修复中的应用. 中国美容医学, 2018, 27(2): 15-18.
17. Narushima M, Mihara M, Yamamoto Y, et al. Hair transplantation for reconstruction of scalp defects using artificial dermis. Dermatol Surg, 2011, 37(9): 1348-1350.
18. Willyard C. Unlocking the secrets of scar-free skin healing. Nature, 2018, 563(7732): S86-S88.
19. Dituri F, Mancarella S, Cigliano A, et al. TGF-β as multifaceted orchestrator in HCC progression: signaling, EMT, immune microenvironment, and novel therapeutic perspectives. Semin Liver Dis, 2019, 39(1): 53-69.
20. Ito M, Yang Z, Andl T, et al. Wnt-dependent de novo hair follicle regeneration in adult mouse skin after wounding. Nature, 2007, 447(7142): 316-320.
21. Li B, Hu W, Ma K, et al. Are hair follicle stem cells promising candidates for wound healing? Expert Opin Biol Ther, 2019, 19(2): 119-128.
22. Mathur AN, Zirak B, Boothby IC, et al. Treg-cell control of a CXCL5-IL-17 inflammatory axis promotes hair-follicle-stem-cell differentiation during skin-barrier repair. Immunity, 2019, 50(3): 655-667.
23. Jensen KB, Collins CA, Nascimento E, et al. Lrig1 expression defines a distinct multipotent stem cell population in mammalian epidermis. Cell Stem Cell, 2009, 4(5): 427-439.
24. Wang X, Chen H, Tian R, et al. Macrophages induce AKT/β-catenin-dependent Lgr5⁺ stem cell activation and hair follicle regeneration through TNF. Nat Commun, 2017, 8: 14091.
25. Snippert HJ, Haegebarth A, Kasper M, et al. Lgr6 marks stem cells in the hair follicle that generate all cell lineages of the skin. Science, 2010, 327(5971): 1385-1389.
26. Heidari F, Yari A, Rasoolijazi H, et al. Bulge hair follicle stem cells accelerate cutaneous wound healing in rats. Wounds, 2016, 28(4): 132-141.
27. Quan R, Du W, Zheng X, et al. VEGF165 induces differentiation of hair follicle stem cells into endothelial cells and plays a role in in vivo angiogenesis. J Cell Mol Med, 2017, 21(8): 1593-1604.
28. Du KT, Deng JQ, He XG, et al. MiR-214 regulates the human hair follicle stem cell proliferation and differentiation by targeting EZH2 and Wnt/β-catenin signaling way in vitro. Tissue Eng Regen Med, 2018, 15(3): 341-350.
29. Choi YS, Zhang Y, Xu M, et al. Distinct functions for Wnt/β-catenin in hair follicle stem cell proliferation and survival and interfollicular epidermal homeostasis. Cell Stem Cell, 2013, 13(6): 720-733.
30. Wei J, Melichian D, Komura K, et al. Canonical Wnt signaling induces skin fibrosis and subcutaneous lipoatrophy: a novel mouse model for scleroderma? Arthritis Rheum, 2011, 63(6): 1707-1717.
31. Cheon SS, Cheah AY, Turley S, et al. beta-Catenin stabilization dysregulates mesenchymal cell proliferation, motility, and invasiveness and causes aggressive fibromatosis and hyperplastic cutaneous wounds. Proc Natl Acad Sci U S A, 2002, 99(10): 6973-6978.
32. Bastakoty D, Saraswati S, Cates J, et al. Inhibition of Wnt/β-catenin pathway promotes regenerative repair of cutaneous and cartilage injury. FASEB J, 2015, 29(12): 4881-4892.
33. Qiu W, Lei M, Li J, et al. Activated hair follicle stem cells and Wnt/β-catenin signaling involve in pathnogenesis of sebaceous neoplasms. Int J Med Sci, 2014, 11(10): 1022-1028.
34. Sato M. Upregulation of the Wnt/beta-catenin pathway induced by transforming growth factor-beta in hypertrophic scars and keloids. Acta Derm Venereol, 2006, 86(4): 300-307.
35. Madaan A, Verma R, Singh AT, et al. Review of hair follicle dermal papilla cells as in vitro screening model for hair growth. Int J Cosmet Sci, 2018, 40(5): 429-450.
36. Rippa AL, Kalabusheva EP, Vorotelyak EA. Regeneration of dermis: scarring and cells involved. Cells, 2019, 8(6): 607.
37. Qi SH, Liu P, Xie JL, et al. Experimental study on repairing of nude mice skin defects with composite skin consisting of xenogeneic dermis and epidermal stem cells and hair follicle dermal papilla cells. Burns, 2008, 34(3): 385-392.
38. Leirós GJ, Kusinsky AG, Drago H, et al. Dermal papilla cells improve the wound healing process and generate hair bud-like structures in grafted skin substitutes using hair follicle stem cells. Stem Cells Transl Med, 2014, 3(10): 1209-1219.
39. Yoshida Y, Soma T, Kishimoto J. Characterization of human dermal sheath cells reveals CD36-expressing perivascular cells associated with capillary blood vessel formation in hair follicles. Biochem Biophys Res Commun, 2019, 516(3): 945-950.
40. Ma D, Kua JE, Lim WK, et al. In vitro characterization of human hair follicle dermal sheath mesenchymal stromal cells and their potential in enhancing diabetic wound healing. Cytotherapy, 2015, 17(8): 1036-1051.
41. Tao Y, Yang Q, Wang L, et al. β-catenin activation in hair follicle dermal stem cells induces ectopic hair outgrowth and skin fibrosis. J Mol Cell Biol, 2019, 11(1): 26-38.
42. 李幼忱, 刘杰, 王德文, 等. 毛囊真皮鞘细胞在皮肤创伤愈合中作用的实验研究. 军事医学科学院院刊, 2009, 33(2): 144-147.
43. Higgins CA, Roger MF, Hill RP, et al. Multifaceted role of hair follicle dermal cells in bioengineered skins. Br J Dermatol, 2017, 176(5): 1259-1269.
44. Kaur P. Hair-follicle dermal papilla and sheath fibroblasts provide a supportive microenvironment for human skin regeneration. Br J Dermatol, 2017, 176(5): 1123-1124.
45. Reynolds AJ, Lawrence C, Cserhalmi-Friedman PB, et al. Trans-gender induction of hair follicles. Nature, 1999, 402(6757): 33-34.

Previous Article
Research progress of adipose-derived stem cells in skin scar prevention and treatment
Next Article
The causes of Latarjet surgery failure and the revision surgeries

Chinese Journal of Reparative and Reconstructive Surgery

Research progress of hair follicle and related stem cells in scar-free wound healing

Abstract Full text Figures/Tables Video References Cited by

Previous Article

Next Article

Format

Content