Sphere Formation Increases the Ability of Cultured Human Dermal Papilla Cells to Induce Hair Follicles from Mouse Epidermal Cells in a Reconstitution Assay

Kang, Byungjun; Kwack, Mi Hee; Kim, Moon Kyu; Kim, Jung Chul; Sung, Young Kwan

doi:10.1038/jid.2011.250

Cited by 81 publications

(71 citation statements)

References 15 publications

(1 reference statement)

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“…In the late 1990s, we demonstrated that intact human dermal sheath was inductive in human skin (14) whereas, more recently, the inductive properties of intact human dermal papilla were exhibited when they were recombined with bulge-derived epithelial cells, isolated from human hair follicles (46). Nevertheless, despite intense interest, until now, the same claim could not be made for cultured human dermal papilla because they have previously been shown to induce only chimeric human/rodent hair follicles in recipient rodent tissues, and not entirely human hair follicles (19,47). Here, we demonstrate that cultured human dermal papilla spheroids are capable of inducing de novo hair follicles in intact recipient human skin.…”

Section: Discussionmentioning

confidence: 86%

“…Nevertheless, within our system, the aggregation of papilla cells in a 3D spheroid enabled partial reprogramming, which in itself was sufficient to initiate hair follicle induction in recipient human tissue. Importantly, as demonstrated when using the murine patch assay (47,50), dermal spheroids are capable of responding to reciprocal signals from the adjacent epithelium. It is in this context that final reprogramming to a dermal papilla likely occurs.…”

Section: Discussionmentioning

confidence: 99%

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

Higgins¹,

Chen

Cerise³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

301

364

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This Feature Article is part of a series identified by the Editorial Board as reporting findings of exceptional significance.Edited by Zena Werb, University of California, San Francisco, CA, and approved September 5, 2013 (received for review May 28, 2013) 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 hairinducing 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.

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Section: Discussionmentioning

confidence: 86%

Section: Discussionmentioning

confidence: 99%

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

Higgins¹,

Chen

Cerise³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

301

364

View full text Add to dashboard Cite

show abstract

“…Growth of mouse dermal papilla cells in spheroid culture can extend their inductive phenotype by several passages compared with monolayer cultures [92]. Moreover, human dermal papilla cells grown as spheroids, and combined with mouse epithelial cells in the patch assay, are capable of inducing hair growth while monolayer cultures lack this capacity [95]. This advance is of great interest, as it is an intrinsic modification of the cells, rather than the introduction of an external factor, that is conferring an inductive effect upon the papilla cells.…”

Section: Regeneration Of Hair Follicles Using Hair Follicle Cell Cultmentioning

confidence: 98%

Regenerative Medicine and Hair Loss: How Hair Follicle Culture has Advanced our Understanding of Treatment Options for Androgenetic Alopecia

Christiano

2013

Regen. Med.

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Many of the current drug therapies for androgenetic alopecia were discovered serendipitously, with hair growth observed as an off-target effect when drugs were used to treat a different disorder. Subsequently, several studies using cultured cells have enabled identification of hair growth modulators with similar properties to the currently available drugs, which may also provide clinical benefit. In situations where the current therapeutics do not work, follicular unit transplantation is an alternative surgical option. More recently, the concept of follicular cell implantation, or hair follicle neogenesis, has been attempted, exploiting the inherent properties of cultured hair follicle cells to induce de novo hair growth in balding scalp. In this review, we discuss both the advances in cell culture techniques that have led to a wider range of potential therapeutics to promote hair growth, in addition to detailing current knowledge on follicular cell implantation, and the challenges in making this approach a reality.

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“…39 “Patch” assays, formed by injecting hDPCs, grown as spheroids, together with mouse epidermal cells in reconstitution, have been shown to increase the ability of cultured hDPCs to induce hair follicles from mouse epidermal cells. 40 A key factor for generating hair follicle–like structures is the use of a mesenchymal component (murine DPCs), which is the same species as the recipient. However, the use of immunodeficient host mice in these in vivo models possesses drawbacks especially when applying these systems to the regeneration of human hair follicles.…”

Section: Dpcs and Hair Follicle Tissue Engineeringmentioning

confidence: 99%

A review of adipocyte lineage cells and dermal papilla cells in hair follicle regeneration

et al. 2014

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Alopecia is an exceedingly prevalent problem effecting men and women of all ages. The standard of care for alopecia involves either transplanting existing hair follicles to bald areas or attempting to stimulate existing follicles with topical and/or oral medication. Yet, these treatment options are fraught with problems of cost, side effects, and, most importantly, inadequate long-term hair coverage. Innovative cell-based therapies have focused on the dermal papilla cell as a way to grow new hair in previously bald areas. However, despite this attention, many obstacles exist, including retention of dermal papilla inducing ability and maintenance of dermal papilla productivity after several passages of culture. The use of adipocyte lineage cells, including adipose-derived stem cells, has shown promise as a cell-based solution to regulate hair regeneration and may help in maintaining or increasing dermal papilla cells inducing hair ability. In this review, we highlight recent advances in the understanding of the cellular contribution and regulation of dermal papilla cells and summarize adipocyte lineage cells in hair regeneration.

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Sphere Formation Increases the Ability of Cultured Human Dermal Papilla Cells to Induce Hair Follicles from Mouse Epidermal Cells in a Reconstitution Assay

Cited by 81 publications

References 15 publications

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

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

Regenerative Medicine and Hair Loss: How Hair Follicle Culture has Advanced our Understanding of Treatment Options for Androgenetic Alopecia

A review of adipocyte lineage cells and dermal papilla cells in hair follicle regeneration

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