Reconstructed human skin shows epidermal invagination towards integrated neopapillae indicating early hair follicle formation in vitro

Vahav, Irit; Broek, Lenie J. van den; Thon, Maria; Monsuur, Hanneke N.; Spiekstra, Sander W.; Ataç, Beren; Scheper, Rik J.; Lauster, Roland; Lindner, G; Marx, Uwe; Gibbs, Susan

doi:10.1002/term.3039

Cited by 32 publications

(45 citation statements)

References 47 publications

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“…2 c). Vimentin is an extracellular matrix component secreted by DP cells while cytokeratin 15 (K15) is an epithelial stem-cell marker 13 , 14 . The cell aggregate containing HUVECs was designated as vHFG.…”

Section: Resultsmentioning

confidence: 99%

Hair follicle germs containing vascular endothelial cells for hair regenerative medicine

Kageyama

Chun

Fukuda

2021

Sci Rep

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Hair regenerative medicine has emerged as a promising approach for the treatment of severe hair loss. Recent advances in three-dimensional tissue engineering, such as formation of hair follicle germs (HFGs), have considerably improved hair regeneration after transplantation in animal models. Here, we proposed an approach for fabricating HFGs containing vascular endothelial cells. Epithelial, dermal papilla, and vascular endothelial cells initially formed a single aggregate, which subsequently became a dumbbell-shaped HFG, wherein the vascular endothelial cells localized in the region of dermal papilla cells. The HFGs containing vascular endothelial cells exhibited higher expression of hair morphogenesis-related genes in vitro, along with higher levels of hair shaft regeneration upon transplantation to the dorsal side of nude mice, than those without vascular endothelial cells. The generated hair follicles represented functional characteristics, such as piloerection, as well as morphological characteristics comparable to those of natural hair shafts. This approach may provide a promising strategy for fabricating tissue grafts with higher hair inductivity for hair regenerative medicine.

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Section: Resultsmentioning

confidence: 99%

Hair follicle germs containing vascular endothelial cells for hair regenerative medicine

Kageyama

Chun

Fukuda

2021

Sci Rep

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“…Thereafter, melanocytes and epidermal cells mixed with the neopapillae to eventually form hair-containing microfollicles with all relevant cell types and structures (Figure 9; Lindner et al, 2011). Additionally, a recent study with neopapillae incorporated in a human full skin equivalent showed an epithelial downgrowth of keratinocytes toward DP spheres and differentiation toward an IRS precursor (Vahav et al, 2020).…”

Section: In Vitro and In Vivo Bioengineered Germs Using Different Cell Populationsmentioning

confidence: 93%

“…Because the main ECM component in the skin is collagen, most studies that track the development of neopapillae employ collagen I scaffolds (Abaci et al, 2018;Lalley and Boyce, 2019;Vahav et al, 2020). When rodent LGR6-positive keratinocytes are loaded in collagen I scaffolds, the keratinocytes are capable of inducing epithelization, hair growth, and angiogenesis in full-thickness wounds (Lough et al, 2016).…”

Section: In Vitro Requirement Of Ecm Proteins For Hf Neogenesismentioning

confidence: 99%

Back to the Future: From Appendage Development Toward Future Human Hair Follicle Neogenesis

Groot

Ulrich

Gho

et al. 2021

Front. Cell Dev. Biol.

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Hair disorders such as alopecia and hirsutism often impact the social and psychological well-being of an individual. This also holds true for patients with severe burns who have lost their hair follicles (HFs). HFs stimulate proper wound healing and prevent scar formation; thus, HF research can benefit numerous patients. Although hair development and hair disorders are intensively studied, human HF development has not been fully elucidated. Research on human fetal material is often subject to restrictions, and thus development, disease, and wound healing studies remain largely dependent on time-consuming and costly animal studies. Although animal experiments have yielded considerable and useful information, it is increasingly recognized that significant differences exist between animal and human skin and that it is important to obtain meaningful human models. Human disease specific models could therefore play a key role in future therapy. To this end, hair organoids or hair-bearing skin-on-chip created from the patient’s own cells can be used. To create such a complex 3D structure, knowledge of hair genesis, i.e., the early developmental process, is indispensable. Thus, uncovering the mechanisms underlying how HF progenitor cells within human fetal skin form hair buds and subsequently HFs is of interest. Organoid studies have shown that nearly all organs can be recapitulated as mini-organs by mimicking embryonic conditions and utilizing the relevant morphogens and extracellular matrix (ECM) proteins. Therefore, knowledge of the cellular and ECM proteins in the skin of human fetuses is critical to understand the evolution of epithelial tissues, including skin appendages. This review aims to provide an overview of our current understanding of the cellular changes occurring during human skin and HF development. We further discuss the potential implementation of this knowledge in establishing a human in vitro model of a full skin substitute containing hair follicles and the subsequent translation to clinical use.

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“…LbL-DPC aggregation is akin to that of primary DPCs and has the capacity to restore HF induction potential in vitro and regenerate HFs in vivo. 97 Other biomaterials that contribute to the restoration of HF-inducive ability include human placenta ECM hydrogel, 98 synthesized ECM 99 and a chitosan/polyvinyl alcohol nanofibre sponge with an open-cell cellular structure, 100 which expands the biomaterial libraries for the optimization of the culture environment in vitro to restore the ability of DPCs to regenerate HFs. 3D printing technology for HF regeneration by recapitulating the physiological 3D organization of cells in the HF microenvironment is an innovative biomimetic approach.…”

Section: In Vivo Strategies For Functional Regeneration Of Hfsmentioning

confidence: 99%

Functional hair follicle regeneration: an updated review

Zhu

Sun

et al. 2021

Sig Transduct Target Ther

114

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The hair follicle (HF) is a highly conserved sensory organ associated with the immune response against pathogens, thermoregulation, sebum production, angiogenesis, neurogenesis and wound healing. Although recent advances in lineage-tracing techniques and the ability to profile gene expression in small populations of cells have increased the understanding of how stem cells operate during hair growth and regeneration, the construction of functional follicles with cycling activity is still a great challenge for the hair research field and for translational and clinical applications. Given that hair formation and cycling rely on tightly coordinated epithelial–mesenchymal interactions, we thus review potential cell sources with HF-inducive capacities and summarize current bioengineering strategies for HF regeneration with functional restoration.

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Reconstructed human skin shows epidermal invagination towards integrated neopapillae indicating early hair follicle formation in vitro

Cited by 32 publications

References 47 publications

Hair follicle germs containing vascular endothelial cells for hair regenerative medicine

Hair follicle germs containing vascular endothelial cells for hair regenerative medicine

Back to the Future: From Appendage Development Toward Future Human Hair Follicle Neogenesis

Functional hair follicle regeneration: an updated review

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