Secreted cytokines by transplanted cells can have positive effects such as immunomodulation, angiogenesis and tissue regeneration. However, transplanted cells are difficult to retain in a specific place to maximize the release of cytokines on site. Here, we developed a hollow electrospun scaffold with one open and one closed end for the in vivo delivery of cells as ?secretory factories? in a hydrogel, termed the hydrocup. Because of the closed end, a (cell-laden) hydrogel can easily be dispensed into the open end of the hydrocup, after which the open end is closed with sutures. As part of the ERC starting grant where this application stems from, we showed that adult stem cells encapsulated inside the hydrocups remained viable for 28 days in vitro and released functional cytokines similar to hMSCs in hydrogels alone. In addition, the hydrocups remained intact and fixed in place for 6 weeks after subcutaneous implantation in rats. In this ERC proof of concept proposal, we aim at further studying the hydrocup as a device for a wide variety of cell-based cytokine secretion or drug-laden hydrogel applications. We will further refine the device for applications in the cardiac regeneration market where stem cell based therapies suffer so far from low viability of cells after injection. We will make a market analysis study of competitors in the cell therapy field and propose an initial business plan for seeking further investments to create a spin-off company at the end of the grant.

The TIME project aims to ascertain the time at which the toxicity observed in classic galactosemia begins, particularly if it begins prenatally. Recent advances in the molecular bases of classic galactosemia have taken research a step further towards therapy development. Therefore, it is of utmost importance to elucidate when the damage accurately begins, in order to define the time at which therapy should be initiated so that it can effectively prevent the development of long-term complications. The Galactosemia Research Group (GRG) in Maastricht has recently developed a zebrafish model of classic galactosemia, which is particularly indicated for studying developmental processes. I will use transient embryological- and whole life-knockout galt-zebrafish to analyze damage in target-organs at different stages of pre- and post-natal development and compare them to the wild-type fish, which will allow determining the exact time of damage onset in classic galactosemia. The GRG is a world-renowned multidisciplinary group that will strongly enhance my professional and personal qualifications as a researcher. In turn, I will contribute with my expertise in molecular bases of rare metabolic disorders. This project constitutes a major milestone for this disorder, as it will allow the development of an effective treatment, which in turn will decrease galactosemic patients' requirement for medical assistance and by making them fit to work and to fully engage in the society. Prof. Patrick Cunningham (Trinity College, Dublin) once said: To be a researcher is not just to be in the laboratory, you work for the world, you work for the society. This sentence illustrates what I have always felt to be my purpose as a researcher. Ever since I initiated my scientific career that I am fully committed in taking research in rare disorders towards the improvement of patients’ health and lives, and this fellowship constitutes an important step towards that commitment.