Human iPS Cell-Derived Cell Aggregates Exhibited Dermal Papilla Cell Properties in in vitro Three-Dimensional Assemblage Mimicking Hair Follicle Structures
| Autor: | Yoshimi Yamazaki, Aki Tsukashima, Masahiro Fukuyama, Manabu Ohyama, Momoko Kimishima, Hideyuki Okano |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
QH301-705.5 Cell dermal papilla 03 medical and health sciences epithelial–mesenchymal interactions 0302 clinical medicine WNT signaling Keratin medicine Biology (General) Induced pluripotent stem cell chemistry.chemical_classification Matrigel hair follicle Chemistry Mesenchymal stem cell Wnt signaling pathway Cell Biology Hair follicle Cell aggregation Cell biology human induced pluripotent stem cells 030104 developmental biology medicine.anatomical_structure regeneration 030217 neurology & neurosurgery Developmental Biology |
| Zdroj: | Frontiers in Cell and Developmental Biology, Vol 9 (2021) |
| ISSN: | 2296-634X |
| DOI: | 10.3389/fcell.2021.590333 |
| Popis: | Current approaches for human hair follicle (HF) regeneration mostly adopt cell-autonomous tissue reassembly in a permissive murine intracorporeal environment. This, together with the limitation in human-derived trichogenic starting materials, potentially hinders the bioengineering of human HF structures, especially for the drug discovery and treatment of hair loss disorders. In this study, we attempted to reproduce the anatomical relationship between an epithelial main body and the dermal papilla (DP) within HFin vitroby three-dimensionally assembling columnarly molded human keratinocytes (KCs) and the aggregates of DP cells and evaluated how HF characteristics were reproduced in the constructs. The replaceability of human-induced pluripotent stem cell (hiPSC)-derived DP substitutes was assessed using the aforementioned reconstruction assay. Human DP cell aggregates were embedded into Matrigel as a cluster. Subsequently, highly condensed human KCs were cylindrically injected onto DP spheroids. After 2-week culture, the structures visually mimicking HFs were obtained. KC-DP constructs partially reproduced HF microanatomy and demonstrated differential keratin (KRT) expression pattern in HFs: KRT14 in the outermost part and KRT13, KRT17, and KRT40, respectively, in the inner portion of the main body. KC-DP constructs tended to upregulate HF-related genes,KRT25,KRT33A,KRT82,WNT5A, andLEF1. Next, DP substitutes were prepared by exposing hiPSC-derived mesenchymal cells to retinoic acid and subsequently to WNT, BMP, and FGF signal activators, followed by cell aggregation. The resultant hiPSC-derived DP substitutes (iDPs) were combined with KCs in the invented assay. KC-iDP constructs morphologically resemble KC-DP constructs and analogously mimicked KRT expression pattern in HF. iDP in the constructs expressed DP-related markers, such as vimentin and versican. Intriguingly, KC-iDP constructs more intensely expressedKRT33A,KRT82, andLEF1, which were stepwisely upregulated by the addition of WNT ligand and the mixture of WNT, SHH, and EDA signaling activators, supporting the idea that iDP exhibited biological properties analogous to DP cell aggregates in the constructsin vitro. These preliminary findings suggested the possibility of regenerating DP equivalents within vitrohair-inductive capacity using hiPSC-derived cell composites, which potentially reduce the necessity of human tissue-derived trichogenic cell subset and eventually allow xeno-free bioengineering of human HFs. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|