Differentiating Human Pluripotent Stem Cells to Dermal Papilla Precursors
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Solution Overview
Problem
Current methods for inducing hair follicle neogenesis using human dermal papilla cells are limited by the rapid loss of hair follicle-forming ability when cultured in vitro, and there is no established protocol for differentiating dermal papilla cells from human pluripotent stem cells with hair follicle-forming ability.
Innovation Solution
A medium composition comprising Dulbecco's Modified Eagle's Medium/Nutrient Mixture F-12 (DMEM/F12) with fibroblast growth factor-2 (FGF2), a glycogen synthase kinase-3 (GSK-3) inhibitor, and bone morphogenetic protein 4 (BMP4) is used to differentiate dermal papilla precursor cells from human pluripotent stem cells, which are then co-cultured with epithelial stem cells to induce hair follicle neogenesis.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If human dermal papilla cells are cultured in vitro, then cell proliferation is achieved, but hair follicle-forming ability is rapidly lost
Solution Approach 1:
The patent applies preliminary action by differentiating human pluripotent stem cells into dermal papilla precursor cells under controlled in vitro conditions before they lose their hair follicle-forming ability. The specific differentiation protocol using DMEM/F12 medium with bFGF and other growth factors creates the desired cell type in advance, preserving the hair follicle-forming capability that would otherwise be lost during prolonged culture.
2Reliability
If human pluripotent stem cells are differentiated into dermal papilla cells, then hair follicle-forming ability is maintained, but there is no established protocol for differentiation
Solution Approach 1:
The patent applies parameter changes by optimizing specific culture conditions including medium composition (DMEM/F12 with defined supplements), growth factor concentrations (bFGF at 2-10 ng/mL, TGF-β at 1-5 ng/mL), and culture duration to achieve successful differentiation of human pluripotent stem cells into dermal papilla precursor cells while maintaining their hair follicle-forming ability.
3Reliability
If dermal papilla cells are used for hair follicle neogenesis, then hair regeneration is achieved, but autologous transplantation is limited in patients with intractable hair loss
Solution Approach 1:
The patent applies universality by using human pluripotent stem cells as a universal starting material that can be differentiated into dermal papilla precursor cells for any patient regardless of their current hair loss status. This approach overcomes the limitation of autologous transplantation by providing a renewable source of hair follicle-forming cells that can be generated from pluripotent stem cells rather than requiring existing healthy hair follicles.
Data Source
AI summary
Provided is a medium composition for differentiation of a human induced pluripotent stem cell to a dermal papilla precursor cell, a differentiation method, and a use for inducing hair follicle neogenesis using the differentiated dermal papilla precursor cell. Further provided is a method for differentiating a human induced pluripotent stem cell into a dermal papilla precursor cell having hair follicle forming ability and a composition of a dermal papilla precursor cell specific differentiation medium for the above differentiation, and have effectively induced hair follicle neogenesis consisting only of human cells without conventional mouse-human hybrid hair follicles by using the human induced dermal papilla precursor cell and a human induced epidermal precursor cell obtained through the differentiation method. Human hair follicle tissue produced is expected to be useful as a therapeutic method for patients suffering from hair loss by overcoming the limitations of hair loss treatments.