Derivation of Hair-Inducing Cell from Human Pluripotent Stem Cells

Abstract

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.

Tissue engineering strategies for human hair follicle regeneration: How far from a hairy goal?

“…To overcome the constraints of cell population scarcity and/or technical isolation, non‐autologous reprogramed pluripotent stem cells have been considered as these represent an inexhaustible source of cells with multi‐lineage differentiation ability . To date, several groups have already attempted HF regeneration using human‐induced pluripotent stem cells (hiPSCs) . Differentiation of hiPSCs obtained from non‐hair cell sources can be used to generate both DPCs and HFSCs, or simply an inductive dermal and receptive epidermal cell population.…”

“…Also, human embryonic stem cells (hESCs) have been tested for differentiation into HF cell lineages. Recently, a two‐step procedure reported the derivation of hESCs into neural crest cells and then hair inductive DP‐like cells . Lastly, recent studies described the transformation of human dermal fibroblasts into hair‐inducing cells with HF regenerative competence …”

“…80 To date, several groups have already attempted HF regeneration using human-induced pluripotent stem cells (hiPSCs). [73][74][75] Differentiation of hiPSCs obtained from non-hair cell sources can be used to generate both DPCs and HFSCs, or simply an inductive dermal and receptive epidermal cell population. Indeed, hiPSCs may enable HF bioengineering through a 3D integumentary organ system in vitro.…”

“…Recently, a two-step procedure reported the derivation of hESCs into neural crest cells and then hair inductive DP-like cells. 75 Lastly, recent studies described the transformation of human dermal fibroblasts into hair-inducing cells with HF regenerative competence. 67,69 In sum, several cellular sources are currently being investigated for human HF bioengineering (Figure 2) that will deliver distinct HF equivalents in vitro with attractive potential to specific research/clinical applications (eg, preclinical models for drug efficacy testing and reconstructed skin models 76,83 ), even if do not answer the demand for functional/cycling/oriented bioengineered HF required for hair cloning.…”

Hair Follicle Reconstruction and Stem Cells

“…For example, the derivation of functional DP-like cells from human embryonic stem cells was recently reported [102]. Derivation of multipotent progenitors of the epithelial lineage [103,104] gives an opportunity to combine trichogenic cells at their early stages of commitment with hopefully beter results.…”