Reno-cardiovascular disease and regeneration: focus on interactions with the immune system

PhD thesis, Merle M. Krebber

The goal of this thesis was to gain insight in how the interplay between inflammation, fibrosis and regeneration in reno-cardiovascular (reno-CVD) disease models influences organ function and how we can improve regenerative medicine (RM) with this knowledge. Our cell-, animal- and dataset-models showed that risk factors associated with reno-CVD have a broad array of effects on these processes. An important finding is however that macrophage-driven inflammation, fibrosis and regeneration primarily appear to be regulated independently. Tailored treatments may be recommended for reno-CVD patients. Novel therapies could focus on interfering with cellular metabolism of specific immune cells, mediating the transition from inflammation to regeneration. Within RM, in situ (in place) tissue engineering (TE) appears promising. Here, a synthetic design in any shape directly replaces non-functional tissue such as a blood vessel. We are the first to show that blood vessel in situ TE combined with a milieu of chronic kidney disease leads to promising results. The characteristics of the degradable synthetic material appear more important than the presence of reno-CVD. Adaptation to the material’s surface could further contribute to improved function of (blood vessel) tissue.