Bioengineering a Human Dermal Equivalent Using Induced Pluripotent Stem Cell-Derived Fibroblasts to Support the Formation of a Full-Thickness Skin Construct

TL;DR

Researchers created a human skin model using stem cell-derived fibroblasts, offering a consistent and customizable alternative to traditional methods.

Contribution

The study introduces a novel method to generate a full-thickness skin construct using iPSC-derived fibroblasts.

Findings

iPSC-derived fibroblasts formed a dermal equivalent with structure and composition similar to primary fibroblasts.

The skin model expressed key skin markers in the organized epidermis, improving on previous models.

The model supports an overlying epidermis and demonstrates potential for customized skin equivalents.

Abstract

In vitro tissue models offer a flexible complementary study system for use alongside in vivo human tissue samples. Achieving accurate in vitro models relies on combining appropriate scaffolds, growth factors and cell populations to recreate human tissue complexity. Balancing a consistent cell supply with the creation of healthy tissue models can be challenging; established cell lines are often cancerous, with altered cellular function compared to healthy populations, and primary cells require repeated isolation, with associated batch-to-batch variation. Pluripotent stem cell-derived populations offer a consistent supply, as well as the ability to model disease phenotypes through cell reprogramming using patient-derived cells. In this study, we have used an induced pluripotent stem cell-derived fibroblast population to develop a dermal equivalent model. These cells form a consistent tissue construct with a structure and composition similar to primary fibroblast controls, which are able to support an overlying epidermis. The resultant full-thickness skin model demonstrates the expression of various key skin-related markers, correctly localised within the organised epidermis, notably improving on previous models of a similar nature. Providing proof of concept using an established in vitro protocol, this study paves the way for future work developing consistent, customised, full-thickness human skin equivalents using iPSC-derived populations.

Figures