Activating β-catenin signaling in CD133-positive dermal papilla cells increases hair inductivity.
Bioengineering hair follicles using cells isolated from human tissue remains a difficult task. Dermal papilla (DP) cells are known to guide the growth and cycling activities of hair follicles by interacting with keratinocytes. However, DP cells quickly lose their inductivity during in vitro passaging. Rodent DP cell cultures need external addition of growth factors, including WNT and BMP molecules, to maintain the hair inductive property. CD133 is expressed by a subpopulation of DP cells that are capable of inducing hair follicle formation in vivo. We report here that expression of a stabilized form of β-catenin promoted clonal growth of CD133-positive (CD133+) DP cells in in vitro three-dimensional hydrogel culture while maintaining expression of DP markers, including alkaline phosphatase (AP), CD133, and integrin α8. After a 2-week in vitro culture, cultured CD133+ DP cells with up-regulated β-catenin activity led to an accelerated in vivo hair growth in reconstituted skin compared to control cells. Further analysis showed that matrix cell proliferation and differentiation were significantly promoted in hair follicles when β-catenin signaling was up-regulated in CD133+ DP cells. Our data highlight an important role for β-catenin signaling in promoting the inductive capability of CD133+ DP cells for in vitro expansion and in vivo hair follicle regeneration, which could potentially be applied to cultured human DP cells.
Division of Pharmaceutical Sciences, College of Pharmacy, University of Cincinnati, OH, USA.
Linli
L
Zhou
Division of Pharmaceutical Sciences, College of Pharmacy, University of Cincinnati, OH, USA.
Kun
K
Yang
Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, PA, USA.
Mingang
M
Xu
Burnett School of Biomedical Sciences, University of Central Florida, Orlando, FL, USA.
Thomas
T
Andl
Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, PA, USA.
Sarah E
SE
Millar
Department of Surgery, College of Medicine, University of Cincinnati, OH, USA.|Research Department, Shriners Hospitals for Children, Cincinnati, OH, USA.
Steven
S
Boyce
Division of Pharmaceutical Sciences, College of Pharmacy, University of Cincinnati, OH, USA.
Yuhang
Y
Zhang
D000071916:AC133 Antigen / Q000032:analysis* / Q000235:genetics; D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D020405:Dermis / Q000166:cytology*; D005347:Fibroblasts / Q000378:metabolism; D018859:Hair Follicle / Q000166:cytology / Q000254:growth & development*; D008822:Mice, Transgenic; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000378:metabolism*
D000071916:AC133 Antigen; C000606024:Prom1 protein, mouse; D051176:beta Catenin
CD133; dermal papilla; hair follicle; regeneration; β-catenin