Stem Cell-Derived Keratinocyte Tissue Engineering

Stem cell-derived keratinocyte tissue engineering harnesses the ability of pluripotent and somatic stem cells to generate functional epidermal cells for reconstructing or repairing human skin. Keratinocytes, the principal cell type in the outer skin layer, are derived through directed differentiation of embryonic stem cells or induced pluripotent stem cells (iPSCs), or by direct lineage reprogramming of accessible somatic cells. In vitro approaches combine stage-specific modulation of signalling pathways—such as TGFβ, BMP, WNT and NOTCH—with defined culture conditions to produce keratinocyte progenitors and mature keratinocytes. These cells can be assembled into two-dimensional sheets, three-dimensional skin equivalents or delivered as cell-secreted microvesicles that carry RNAs and proteins critical for matrix remodelling, re-epithelialisation and vascularisation. Advances in good-manufacturing-practice-compliant protocols have enabled the production of clinical-grade composites incorporating keratinocytes and fibroblasts within biomimetic scaffolds or fibrin matrices. The convergence of cell biology, materials science and translational medicine has established a versatile toolkit for treating burns, chronic wounds, genetic skin disorders and for modelling epidermal development and disease in vitro.

Research from Nature Portfolio

Recent studies have demonstrated that iPSC-derived microvesicles encapsulating specific mRNAs and proteins can upregulate collagen Iα1 and III expression in dermal fibroblasts without altering their proliferative capacity or stemness markers. In rodent burn models, local administration of these microvesicles accelerates re-epithelialisation and neovascularisation while avoiding significant immune activation. This work underlines the potential of cell-free, microvesicle-based therapies as adjuncts or alternatives to cell transplantation for skin regeneration.

Stem Cell-Derived Keratinocyte Tissue Engineering publication trend

The graph below shows the total number of articles in stem cell-derived keratinocyte tissue engineering across all publications each year (not limited to Nature Index journals).

Technical terms

Induced pluripotent stem cell (iPSC): A somatic cell reprogrammed to an embryonic-like pluripotent state capable of differentiating into various cell types.

Keratinocyte: The predominant epithelial cell in the epidermis responsible for barrier formation and continuous tissue renewal.

Microvesicle: A membrane-bound extracellular vesicle released by cells that transports proteins, lipids and nucleic acids to recipient cells.

Re-epithelialisation: The process by which epithelial cells migrate, proliferate and cover a wound surface during skin repair.

Good Manufacturing Practice (GMP): A system ensuring that products are consistently produced and controlled according to quality standards for clinical use.

References

1. Transcriptomic and in vivo approaches introduced human iPSC-derived microvesicles for skin rejuvenation. Scientific Reports (2023).
2. Long-term expansion of directly reprogrammed keratinocyte-like cells and in vitro reconstitution of human skin. Journal of Biomedical Science (2020).
3. Stagewise keratinocyte differentiation from human embryonic stem cells by defined signal transduction modulators. International Journal of Biological Sciences (2020).
4. Clinical Grade Human Pluripotent Stem Cell-Derived Engineered Skin Substitutes Promote Keratinocytes Wound Closure In Vitro. Cells (2022).