Platform for Alternative Skin Tests for sustainable FUTURE science

This project will create a “Platform for Alternative Skin Tests for sustainable Future science” (PAST4FUTURE) which aims to generate general, versatile and sustainable cell sources for the development and implementation of organotypic models in which skin biology and skin diseases can be studied and therapeutics can be screened. PAST4FUTURE will foster the development, targeted optimisation and benchmarking of user-friendly and freely available organotypic skin models by a public private partnership of four science institutes leading the field of experimental dermatology in The Netherlands with two industrial partners active in the field of antibiotics development (TropIQ) and cell culture supplies (CELLnTEC).

The skin is at the interface between the body and the external world, thus playing a major role in protecting and fostering the life it encloses. Skin health and a normal skin appearance is a major denominator of human wellbeing. Unfortunately, many people suffer from skin conditions ranging from benign mild conditions like dry and sensitive skin, to more severe chronic inflammatory disease like psoriasis, atopic eczema or acne and malignant skin cancers. Research aimed at the fundamental understanding of skin function or at the development of dermatological therapies heavily relies on experimental animal models since molecular manipulation is not compatible with the currently available alternative models to study biological processes in the skin. The implementation of alternative organotypic skin models, basically little pieces of cultured skin, in academia is falling behind considering the lack in flexibility in the model development and experimental challenges regarding the genome editing protocols for human skin cells.

This project will create a powerful momentum to fuel experimental and industrial use of alternatives and empower researchers worldwide to make the change and replace experimental animals by organotypic models of human skin. The development of large scale and more complex multi-cellular human skin measurement models in the future will be accelerated by this first ever nation-wide collaboration of experts in the field of skin tissue engineering by the following project objectives/deliverables:

1. Constructing immortalised keratinocyte cell lines amenable for genome editing strategies
2. Creating a sustainable keratinocyte cell source from well characterised, freely available hiPSC lines
3. Development of standardised, consumer friendly laboratory protocols
4. Benchmarking and multi-site testing for validation of the organotypic skin models
5. Generating high-end (single cell) transcriptomic profiles of organotypic skin models
6. Providing proof-of-concept studies for:

• 6.1 – Genome editing to replace (conditional) knockout or transgenic mice
• 6.2 – Host-microbe interaction in organotypic skin
• 6.3 – Screening of antibiotic activity in physiologically relevant models