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Growth of de novo hair follicles in adult skin occurs by a process known as hair neogenesis. One way of initiating neogenesis is to place dermal papillae isolated from the hair follicle in contact with an overlying epidermis where they reprogram the epidermis to adopt a follicular fate. This approach, however, has not been successful using cultured human dermal papilla cells in human skin because the cells lose their ability to induce hair growth after expansion in vitro. In this paper, we demonstrate that by manipulating cell culture conditions to establish three-dimensional papilla spheroids, we restore dermal papilla inductivity. We also use several systems biology approaches to gain a comprehensive understanding of the molecular mechanisms that underlie this regenerative process.
Growth of de novo hair follicles in adult skin occurs by a process known as hair neogenesis. One way of initiating neogenesis is to place dermal papillae isolated from the hair follicle in contact with an overlying epidermis where they reprogram the epidermis to adopt a follicular fate. This approach, however, has not been successful using cultured human dermal papilla cells in human skin because the cells lose their ability to induce hair growth after expansion in vitro. In this paper, we demonstrate that by manipulating cell culture conditions to establish three-dimensional papilla spheroids, we restore dermal papilla inductivity. We also use several systems biology approaches to gain a comprehensive understanding of the molecular mechanisms that underlie this regenerative process.
In conclusion, we have demonstrated that adult human hair-follicle dermal papilla cells can be partially reprogrammed to become capable of inducing hair-follicle neogenesis simply by manipulating their cellular microenvironment. This partial reprogramming in itself is sufficient to initiate hair-follicle neogenesis in non-hair-bearing human skin; however, we have identified several additional transcriptional regulators that we predict will enable complete recapitulation of the genetic profile of a fully functioning dermal papilla. These findings represent a significant advance within the field of tissue engineering as it relates to cellular therapy of the skin and hair follicle.
Over many decades, a large body of literature has demonstrated that epithelial–mesenchymal interactions result in secondary induction and organ development. Here, we show a dramatic example of how organ neogenesis can be achieved by exploiting the inherent properties of interacting cells to create new structures. We show that it is possible to harness the inductive properties of adult cells to direct de novo organogenesis and translate this concept to demonstrate that cultured human dermal papilla cells can instruct and initiate human hair-follicle induction. Although further work will be required to increase the efficiency of this process, this crucial first step represents a milestone advance for bioengineering of human hair.
Growth of de novo hair follicles in adult skin occurs by a process known as hair neogenesis. One way of initiating neogenesis is to place dermal papillae isolated from the hair follicle in contact with an overlying epidermis where they reprogram the epidermis to adopt a follicular fate. This approach, however, has not been successful using cultured human dermal papilla cells in human skin because the cells lose their ability to induce hair growth after expansion in vitro. In this paper, we demonstrate that by manipulating cell culture conditions to establish three-dimensional papilla spheroids, we restore dermal papilla inductivity. We also use several systems biology approaches to gain a comprehensive understanding of the molecular mechanisms that underlie this regenerative process.
Growth of de novo hair follicles in adult skin occurs by a process known as hair neogenesis. One way of initiating neogenesis is to place dermal papillae isolated from the hair follicle in contact with an overlying epidermis where they reprogram the epidermis to adopt a follicular fate. This approach, however, has not been successful using cultured human dermal papilla cells in human skin because the cells lose their ability to induce hair growth after expansion in vitro. In this paper, we demonstrate that by manipulating cell culture conditions to establish three-dimensional papilla spheroids, we restore dermal papilla inductivity. We also use several systems biology approaches to gain a comprehensive understanding of the molecular mechanisms that underlie this regenerative process.
In conclusion, we have demonstrated that adult human hair-follicle dermal papilla cells can be partially reprogrammed to become capable of inducing hair-follicle neogenesis simply by manipulating their cellular microenvironment. This partial reprogramming in itself is sufficient to initiate hair-follicle neogenesis in non-hair-bearing human skin; however, we have identified several additional transcriptional regulators that we predict will enable complete recapitulation of the genetic profile of a fully functioning dermal papilla. These findings represent a significant advance within the field of tissue engineering as it relates to cellular therapy of the skin and hair follicle.
Over many decades, a large body of literature has demonstrated that epithelial–mesenchymal interactions result in secondary induction and organ development. Here, we show a dramatic example of how organ neogenesis can be achieved by exploiting the inherent properties of interacting cells to create new structures. We show that it is possible to harness the inductive properties of adult cells to direct de novo organogenesis and translate this concept to demonstrate that cultured human dermal papilla cells can instruct and initiate human hair-follicle induction. Although further work will be required to increase the efficiency of this process, this crucial first step represents a milestone advance for bioengineering of human hair.
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