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Cell-Based Models of Human Mucosal Immunity with Multiple Commercial Applications

Final Report Summary - HUMUNITY (Cell-Based Models of Human Mucosal Immunity with Multiple Commercial Applications)

HUMUNITY (Cell-Based Models of Human Mucosal Immunity with Multiple Commercial Applications; has been a PhD school that trained young scientists in advanced human cell culture and analysis, and taught the processes for their translation into industrially-exploitable and medically-useful tools. The scientific goal was to develop advanced cell-biological models in which different types of human primary cells mimic in culture the architecture and the interactions of the original tissue. Specifically, students were engaged in developing novel systems in which the innate inflammatory response to agents presented at mucosal surfaces (lung, gut) were studied in both healthy and pathological conditions. These culture systems were the basis for development of preclinical models with multiple applications, from testing of candidate therapeutics or health-promoting agents to screening for health risk from environmental or dietary contaminants. Collectively, these models have robustly reproduced the reactivity of human tissues in vivo, a finding that is important for future strategies of reduction of animal experimentation.

HUMUNITY aimed at delivering industry-oriented PhD training in the field of advanced in vitro models. The four selected Early-Stage Researchers (ESRs) have experienced an intersectoral training programme encompassing an 18-month internship in a UK SME (AvantiCell Science Ltd., ACS), expert in isolation and culture of human primary cells, and 18 months in the Laboratory of Innate Immunity and Inflammation of the Italian National Research Council (CNR). Secondments to the associated partners University of Pisa (UNIPI, Italy) and Paris-Lodron University of Salzburg (PLUS, Austria) have been performed during the fellowships. Students have been enrolled in the PhD programme of PLUS, have been engaged in training-by-research, and participated in a series of scientific and technical training courses provided by each institution. Fellows also participated to joint scientific meetings and transferable skills courses organised by the associated partner ALTA. The trainees also gained experience in transferring their technology to relevant industry sectors, from pharmaceutical, food and healthcare to environmental safety.

ESR1 has spent the first 18 months at CNR, being engaged in differentiating mucosal-like dendritic cells to be included in the lung model. In the industrial internship at ACS, the fellow worked at setting up human primary bronchial epithelial cell cultures, necessary for assembling the in vitro co-culture model of healthy lung.
ESR2 started at ACS by working at isolation and characterisation of human primary lung epithelial cells, and engaged in a thorough study of cryopreservation procedures. During the subsequent stay at CNR, the fellow assembled and validated co-cultures of human primary monocytes and inflamed lung epithelial cells that mimicked a pathological lung tissue.
ESR3 at CNR did set up a protocol for differentiating human primary monocytes into gut tissue-like macrophages, and studied their reactivity to various inflammatory and infectious stimuli as compared to circulating monocytes in 2D cultures and in the present of matrigel scaffolds. At ACS, the fellow has developed and refined the technique for isolating primary enterocytes, starting from bovine tissue, providing to the company a new technology of significant commercial value.
ESR4 has worked at ACS at isolating and characterising bovine and human gut cells for the in vitro model of inflamed gut. At CNR the fellow has assembled a co-culture model using differentiated Caco-2 cells as epithelial partner and human gut-like macrophages and innate immune counterpart, and tested and validated it.

All fellows have actively participated to outreach activities: seminars and demonstrations to secondary school kids and demonstrations to the general public during science fairs.

All fellows have successfully presented their research results during the two project meetings (Naples, October 2014; Salzburg, September 2015). Apart from ESR1, who resigned on August 2016, all fellows presented their final results to the HUMUNITY workshop “Novel In Vitro Methods for Assessing Human Innate Responses at the Mucosal Level” organised in Naples on September 2016.
They also participated to several training activities organised by the beneficiaries and Associated Partners, including three Short Courses of Transferable training/SCTs).
The SCTs have been organised by the Associated Partner ALTA, in conjunction with the scientific events, and consisted in a series of lessons and lectures dealing with:
• Scientific Communication and Grant Writing Skills (Naples, October 2014).
• Ethical issues (Salzburg, September 2015).
• Entrepreneurship and Marketing Strategies (Naples, September 2016).

Eventually, they have jointly written and published a review paper in “International Trends in Immunity” in November 2014, and contributed to other three peer-reviewed articles.
Apart from ESR1 who dropped the PhD enrolment, the fellows are currently preparing scientific articles and the PhD theses, which will be defended at the Associated Partner PLUS in 2017.

The logo of the HUMUNITY project is attached.