Derivation of hair-inducing cell from human pluripotent stem cells

Dermal Papillae (DP) is a unique population of mesenchymal cells that was shown to regulate hair follicle formation and growth cycle. During development most DP cells are derived from mesoderm, however, functionally equivalent DP cells of cephalic hairs originate from Neural Crest (NC). Here we dire...

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Veröffentlicht in:PloS one 2015-01, Vol.10 (1), p.e0116892-e0116892
Hauptverfasser: Gnedeva, Ksenia, Vorotelyak, Ekaterina, Cimadamore, Flavio, Cattarossi, Giulio, Giusto, Elena, Terskikh, Vasiliy V, Terskikh, Alexey V
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creator Gnedeva, Ksenia
Vorotelyak, Ekaterina
Cimadamore, Flavio
Cattarossi, Giulio
Giusto, Elena
Terskikh, Vasiliy V
Terskikh, Alexey V
description Dermal Papillae (DP) is a unique population of mesenchymal cells that was shown to regulate hair follicle formation and growth cycle. During development most DP cells are derived from mesoderm, however, functionally equivalent DP cells of cephalic hairs originate from Neural Crest (NC). Here we directed human embryonic stem cells (hESCs) to generate first NC cells and then hair-inducing DP-like cells in culture. We showed that hESC-derived DP-like cells (hESC-DPs) express markers typically found in adult human DP cells (e.g., p-75, nestin, versican, SMA, alkaline phosphatase) and are able to induce hair follicle formation when transplanted under the skin of immunodeficient NUDE mice. Engineered to express GFP, hESC-derived DP-like cells incorporate into DP of newly formed hair follicles and express appropriate markers. We demonstrated that BMP signaling is critical for hESC-DP derivation since BMP inhibitor dorsomorphin completely eliminated hair-inducing activity from hESC-DP cultures. DP cells were proposed as the cell-based treatment for hair loss diseases. Unfortunately human DP cells are not suitable for this purpose because they cannot be obtained in necessary amounts and rapidly loose their ability to induce hair follicle formation when cultured. In this context derivation of functional hESC-DP cells capable of inducing a robust hair growth for the first time shown here can become an important finding for the biomedical science.
doi_str_mv 10.1371/journal.pone.0116892
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During development most DP cells are derived from mesoderm, however, functionally equivalent DP cells of cephalic hairs originate from Neural Crest (NC). Here we directed human embryonic stem cells (hESCs) to generate first NC cells and then hair-inducing DP-like cells in culture. We showed that hESC-derived DP-like cells (hESC-DPs) express markers typically found in adult human DP cells (e.g., p-75, nestin, versican, SMA, alkaline phosphatase) and are able to induce hair follicle formation when transplanted under the skin of immunodeficient NUDE mice. Engineered to express GFP, hESC-derived DP-like cells incorporate into DP of newly formed hair follicles and express appropriate markers. We demonstrated that BMP signaling is critical for hESC-DP derivation since BMP inhibitor dorsomorphin completely eliminated hair-inducing activity from hESC-DP cultures. DP cells were proposed as the cell-based treatment for hair loss diseases. Unfortunately human DP cells are not suitable for this purpose because they cannot be obtained in necessary amounts and rapidly loose their ability to induce hair follicle formation when cultured. 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Unfortunately human DP cells are not suitable for this purpose because they cannot be obtained in necessary amounts and rapidly loose their ability to induce hair follicle formation when cultured. In this context derivation of functional hESC-DP cells capable of inducing a robust hair growth for the first time shown here can become an important finding for the biomedical science.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>25607935</pmid><doi>10.1371/journal.pone.0116892</doi><oa>free_for_read</oa></addata></record>
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subjects Alkaline phosphatase
Animals
Biomarkers
Biomarkers - metabolism
Bone morphogenetic proteins
Cell culture
Cell Differentiation
Cells, Cultured
Derivation
Embryo cells
Embryonic stem cells
Embryos
Epigenetics
Flow cytometry
Follicles
Gene expression
Hair
Hair Follicle - cytology
Hair Follicle - drug effects
Hair Follicle - growth & development
Hair Follicle - metabolism
Human Embryonic Stem Cells - cytology
Human Embryonic Stem Cells - metabolism
Human Embryonic Stem Cells - transplantation
Humans
Immunodeficiency
Intermediate filament proteins
Medical treatment
Mesenchyme
Mesoderm
Mesoderm - cytology
Mesoderm - metabolism
Mice
Mice, Nude
Nestin
Neural crest
Neural Crest - cytology
Neural Crest - metabolism
Papillae
Phosphatase
Pluripotency
Pyrazoles - pharmacology
Pyrimidines - pharmacology
Signaling
Skin
Stem cell transplantation
Stem cells
Versican
title Derivation of hair-inducing cell from human pluripotent stem cells
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