Microenvironmental reprogramming by three-dimensional culture enables dermal papilla cells to induce de novo human hair-follicle growth.

De novo organ regeneration has been observed in several lower organisms, as well as rodents; however, demonstrating these regenerative properties in human cells and tissues has been challenging. In the hair follicle, rodent hair follicle-derived dermal cells can interact with local epithelia and induce de novo hair follicles in a variety of hairless recipient skin sites. However, multiple attempts to recapitulate this process in humans using human dermal papilla cells in human skin have failed, suggesting that human dermal papilla cells lose key inductive properties upon culture. Here, we performed global gene expression analysis of human dermal papilla cells in culture and discovered very rapid and profound molecular signature changes linking their transition from a 3D to a 2D environment with early loss of their hair-inducing capacity. We demonstrate that the intact dermal papilla transcriptional signature can be partially restored by growth of papilla cells in 3D spheroid cultures. This signature change translates to a partial restoration of inductive capability, and we show that human dermal papilla cells, when grown as spheroids, are capable of inducing de novo hair follicles in human skin

Multifaceted role of hair follicle dermal cells in bioengineered skins

Background The method of generating bioengineered skin constructs was pioneered several decades ago; nowadays these constructs are used regularly for the treatment of severe burns and nonhealing wounds. Commonly, these constructs are comprised of skin fibroblasts within a collagen scaffold, forming the skin dermis, and stratified keratinocytes overlying this, forming the skin epidermis. In the past decade there has been a surge of interest in bioengineered skins, with researchers seeking alternative cell sources, or scaffolds, from which constructs can be established, and for more biomimetic equivalents with skin appendages. Objectives To evaluate whether human hair follicle dermal cells can act as an alternative cell source for engineering the dermal component of engineered skin constructs. Methods We established in vitro skin constructs by incorporating into the collagenous dermal compartment: (i) primary interfollicular dermal fibroblasts, (ii) hair follicle dermal papilla cells or (iii) hair follicle dermal sheath cells. In vivo skins were established by mixing dermal cells and keratinocytes in chambers on top of immunologically compromised mice. Results All fibroblast subtypes were capable of supporting growth of overlying epithelial cells, both in vitro and in vivo. However, we found hair follicle dermal sheath cells to be superior to fibroblasts in their capacity to influence the establishment of a basal lamina. Conclusions Human hair follicle dermal cells can be readily interchanged with interfollicular fibroblasts and used as an alternative cell source for establishing the dermal component of engineered skin both in vitro and in vivo

A spontaneous mutation in the desmoglein 4 gene underlies hypotrichosis in a new lanceolate hair rat model

A recessive hairless mutation arose spontaneously in a congenic line of spontaneously hypertensive rats SHR.BN-(D1mit3-Igf2)/Ipcv. The mutant rats develop generalized alopecia except for partial hair growth on their heads. Affected animals of the congenic line were crossed with LEW rats and randomly bred for several generations. A genome scan in 74 affected and 75 unaffected offspring localized the mutant gene on rat chromosome 18pl2, near the marker D18Rat107, which is closely linked to the desmosomal cadherin gene cluster, syntenic to mouse chromosome 18 and human chromosome 18q12. Recently, the mouse and rat phenotypes lah/lah (lanceolate hair) and lah J/lah J(lanceolate hair-J) were found to be caused by mutations in the desmoglein 4 (Dsg4) gene. Direct sequencing of the Dsg4 gene in the SHR revealed a homozygous C-to-T transition generating a premature termination codon within exon 8 in the affected animals. Further studies on the skin histology in affected rats demonstrated features consistent with a lanceolate hair mutation, providing further support for the crucial role of desmoglein 4 in hair shaft differentiation