C7 N: Cardiac function after trauma and MSC-based regenerative strategies

PI: M. Kalbitz, H. Schrezenmeier

Heart injury was identified as an independent predictor for poor outcome after trauma. However, little is known about the molecular mechanisms of posttraumatic cardiac dysfunction. Therefore, the first part of the study will investigate the consequences of experimental blunt chest trauma or femur fracture and the combination of both as a result of direct mechanical damage and systemic inflammation on cardiac function in mice. Besides cardiac function molecular and structural alterations and gap junction pathologies as well as local and systemic inflammation will be evaluated and correlated. As a second goal of the study underlying molecular mechanisms of posttraumatic cardiac dysfunction will be elucidated. Here, human and murine cardiomyocytes (CMs) will be exposed to trauma-relevant inflammation and damage molecules (e.g. IL-1β, IL-6, TNF, complement activation products C5a and C3a, HMGB-1, extracellular histones and cfDNA, as well as trauma sera). Cardiac damage markers such as troponin and heart-type fatty acid binding protein in cell culture supernatants will be analyzed. Furthermore, cultured CMs will be examined e.g. concerning altered calcium handling, electrophysiological parameters such as resting membrane potential, contractile function, inflammation, mitochondrial pathologies and gap junction modifications. In co-culture experiments the influence of mesenchymal stromal cells (MSC) and MSC-derived effectors on CMs exposed to inflammation and damage molecules will be determined. In the third part of the study, we aim to investigate in vivo whether MSCs or MSC-derived effectors may have a protective effect on cardiac function after trauma. For this cardiac tissue will be examined with regard to molecular, cellular and functional alterations.

Projektleiter

PD Dr. Med. Miriam Kalbitz
Universitätsklinikum Ulm
Zentrum für Chirurgie, Klinik für Unfall-, Hand-, Plastische und Wiederherstellungschirurgie
Albert-Einstein-Allee 23
89081 Ulm
Tel.: +49 731 500 54561
E-mail: miriam.kalbitz(at)uniklinik-ulm.de


Prof. Dr. med. Hubert Schrezenmeier
Universitätsklinikum Ulm
Institut für Transfusionsmedizin
Helmholtzstraße 10
89081 Ulm
Tel.: +49 731 150 550
E-mail: h.schrezenmeier(at)blutspende.de