Scalable production of controllable dermal papilla spheroids on PVA surfaces and the effects of spheroid size on hair follicle regeneration

Huang, Yi‐Ching; Chan, Chih‐Chieh; Lin, Wei-Cheng; Chiu, Hsien-Yi; Tsai, Ren‐Yeu; Tsai, Tsung‐Hua; Chan, Jung-Yi; Lin, Sung‐Jan

doi:10.1016/j.biomaterials.2012.09.083

Cited by 94 publications

(102 citation statements)

References 45 publications

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“…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%

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.

319

379

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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: 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.

319

379

View full text Add to dashboard Cite

show abstract

“…One focus of effort has been on replacing injured hair follicles from scratch, essentially recapitulating the developmental process in vivo or in vitro. Methods for the expansion of both rodent and human DP cells in culture that either maintain or restore their trichogenic activity have been reported (Kishimoto et al 2000;Shimizu and Morgan 2004;Osada et al 2007;Rendl et al 2008;Soma et al 2012;Huang et al 2013;Thangapazham et al 2014). The trichogenic activity of human DP cells has been shown on murine keratinocytes.…”

Section: The Dp In Hair Loss and Restorationmentioning

confidence: 99%

The Dermal Papilla: An Instructive Niche for Epithelial Stem and Progenitor Cells in Development and Regeneration of the Hair Follicle

Morgan

2014

Cold Spring Harbor Perspectives in Medicine

181

151

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The dermal papilla (DP) of the hair follicle is both a chemical and physical niche for epithelial progenitor cells that regenerate the cycling portion of the hair follicle and generate the hair shaft. Here, we review experiments that revealed the importance of the DP in regulating the characteristics of the hair shaft and frequency of hair follicle regeneration. More recent work showed that the size of this niche is dynamic and actively regulated and reduction in DP cell number per follicle is sufficient to cause hair thinning and loss. The formation of the DP during follicle neogenesis provides a context to contemplate the mechanisms that maintain DP size and the potential to exploit these processes for hair preservation or restoration.

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“…Recently, non-cell adherent polymers have been utilized for 3D spheroid formation and culture. [7][8][9] In this case, cells may not adhere to the substrate but could form spheroids on the non-adherent substrate because cell-cell interactions are favored over cell-substrate interactions. In this regard, chitosan, a deacetylated chitin, has been widely studied as a non-adherent polymer to promote the formation of self-assembled 3D cellular spheroids.…”

Section: Introductionmentioning

confidence: 99%

Bioinspired tuning of glycol chitosan for 3D cell culture

Cho

Shim

et al. 2016

NPG Asia Mater

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Three-dimensional (3D) cell culture systems have promising applications compared with conventional two-dimensional cell culture systems. Herein, we report a facile method for the formation of 3D spheroids using novel thermo-reversible polysaccharide-based hydrogels. A series of thermo-reversible hydrogels consisting of N-acyl glycol chitosans (NAGCs) are synthesized through a simple N-acylation reaction, and the degree of acylation is finely tuned to obtain adequate thermoreversible properties and gel stability. Among the NAGCs, N-hexanoyl glycol chitosan is the most thermo-sensitive and is highly effective for forming multi-cellular spheroids when used to coat the surfaces of cell culture dishes. Cell spheroids are effectively formed at various cell concentrations, and their spheroid shape and cellular functions are well maintained for longer times. The hydrogel culture system is also useful for co-cultures that mimic a biological microenvironment. Our thermo-reversible hydrogels may offer a convenient method for the development of in vitro 3D cell culture systems to provide enhanced performance in tissue regeneration, organ-on-chips, drug screening research and other biomedical applications.

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Scalable production of controllable dermal papilla spheroids on PVA surfaces and the effects of spheroid size on hair follicle regeneration

Cited by 94 publications

References 45 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

The Dermal Papilla: An Instructive Niche for Epithelial Stem and Progenitor Cells in Development and Regeneration of the Hair Follicle

Bioinspired tuning of glycol chitosan for 3D cell culture

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