Assembling Composite Dermal Papilla Spheres with Adipose-derived Stem Cells to Enhance Hair Follicle Induction.

Chin-Fu Huang,Cheng-Ming Chuong,Chia-Wei Huang,Ya-Ju Chang,Tzu-Chieh Huang,Yuan-Yu Hsueh,Yi-Ting Wu,Fong-Chin Su,Michael Hughes,Chia-Ching Wu,Duo-Hsiang Wang

doi:10.1038/srep26436

Abstract

Intradermal adipose tissue plays an essential role for hair follicles (HFs) regeneration by regulating hair cycles. However, the effect of reconstruction of HFs and the involvement of adipose-related cells are poorly understood. We investigated assembly strategies for the interactions of dermal papilla (DP) cells with adipose-derived stem cells (ASCs) in promoting hair formation. DP cells lose DP traits during adherent culture, but preserved DP markers with a unified sphere diameter by seeding on chitosan-coated microenvironments. Next, ASCs isolated from rats were co-cultured with DP spheres by different assembling approaches to determine their interactions; a mixed sphere of ASCs with DP cells (MA-DPS), or a core-shell structure, outer ASCs shell and an inner DP core (CSA-DPS). CSA-DPS exhibited superior DP characteristics compared to MA-DPS. Conditional medium from ASCs, but not differentiated adipocytes, promoted DP markers and functional alkaline phosphatase activity from the DP cells. In vivo patch assay showed the core-shell assembling of CSA-DPS can reconstruct cellular arrangements and microenvironmental niches as dominated by PPARα signal in ASCs to induce the greater hair induction than MA-DPS or DP spheres alone. Therefore, the assembling of a core-shell sphere for DP with ASCs could reconstruct the HF cellular arrangement for hair formation. This paper set the groundwork for further evaluation of the input of other cell types.

Highlights

Hair loss or alopecia is associated with aging or hormonal perturbance in males and females that results in the loss of follicular stem cell activity to form hair germs for hair follicle regeneration[1]
The dermal papilla (DP) characteristics can be preserved in 3D microenvironments by chitosan-coating surface
To maintain the DP characteristics in culturing of adherent DP cells, several previous studies proposed various methods; the addition of Wnt3a, bone morphogenetic protein 6 (BMP6), or FGF2 to mouse DP cells[15,29,30], the culture of rat DP cells with conditional media (CM) harvested from sole skin KC31, and the supplement of human DP cells with CM from neonatal foreskin KC32

Summary

Introduction

Hair loss or alopecia is associated with aging or hormonal perturbance in males and females that results in the loss of follicular stem cell activity to form hair germs for hair follicle regeneration[1]. The activity of hair stem cells can be influenced by the microenvironment inside the HFs or the macroenvironmnet outside the HFs. The mature HF is a complex structure which contains several concentric epithelial cylinders of keratinocytes and a specialized mesenchyme of dermal papilla (DP) cells. Some cells have potential hair-inductive capacity, including DP cells, dermal sheath cells, skin-derived precursor cells, and mesenchymal stem cells (MSCs)[11]. During the telogen-to-anagen transition, adipocyte progenitor cells are activated to proliferate and form mature adipocytes surrounding the regenerating HF26. This outer layer of MSC-like cells surrounding the DPs may optimize the microenvironment to promote hair growth. The roles of different adipose-related cells in HF formation or regeneration and tissue engineering are still unknown, especially in the contribution of PPAR signaling from ASCs or mature adipocytes.

Methods

Results

Conclusion