Self-assembly of differentiated progenitor cells facilitates spheroid human skin organoid formation and planar skin regeneration

Theranostics, 2021 · DOI: 10.7150/thno.59661 · Published: July 25, 2021

Biomedical Dermatology Regenerative Medicine & Stem Cells

Simple Explanation

This study explores the creation of skin-like structures from skin cells. The researchers were able to grow both a 3D ball-shaped structure and a flat skin layer. The process involved using human platelet lysate, which is rich in growth factors. These factors helped the skin cells organize themselves into the desired structures. The generated skin structures could potentially be used for drug testing or to help heal severe skin wounds.

Study Duration

Not specified

Participants

Human tissues from healthy donors (8 donors for skin, 3 for umbilical cord blood) and immune-deficient NOD.Cg-Prkdcscid Il2rgtm1WjI/SzJ mice

Evidence Level

Level 3; Experimental study using in vitro and in vivo models

Key Findings

1
Adult and iPSC-derived fibroblasts, keratinocytes, and endothelial progenitors can self-assemble into both planar human skin in vivo and spheroid-shaped skin organoids in vitro.
2
Human platelet lysate (hPL) promotes the self-organization and de novo transplant vasculogenesis, mimicking wound repair processes in vitro and in vivo.
3
Transplantation of hiPSC-derived single-cell suspensions resulted in proper organization into epidermal and dermal layers with proliferating cells in the basal keratinocyte layer.

Research Summary

The study demonstrates the self-assembly of skin progenitor cells into vascularized spheroid floating skin organoids (FSOs) in vitro and properly stratified rapidly vascularized human skin in vivo. Human platelet lysate (hPL) plays a critical role in orchestrating self-organization and de novo transplant vasculogenesis, mimicking wound repair processes. hiPSC-derived skin cells can be generated and used for self-assembly into skin organoids and for single-cell suspension transplants, resulting in the formation of human skin in vivo.

Practical Implications

Drug Testing

The spheroid skin organoids (FSOs) can be used for rapid 3D skin-related pharmaceutical high-content testing opportunities.

Wound Healing

Multi-cell transplant self-organization facilitates the development of iPSC-based organ regeneration strategies using cell suspension transplantation supported by human platelet factors, potentially improving wound healing.

Spray-on Skin Improvement

Addition of hPL to transplanted cell suspensions in spray-on skin applications might offer the opportunity to better repair wounds with small amounts of regional cells.

Study Limitations

1
The engineered skin transplants lack hair and skin appendages, limiting their complexity compared to native skin.
2
The study lacks mechanistic explanations for the cell self-assembly in the presence of hPL.
3
Clinical application without immune suppression will depend on either using autologous cells or histocompatible iPSC sources.

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