Extracellular Biotechnology

Selected Publications

Tissue Regeneration and Aging

Regenerative capacity of organs and tissues decreases with age and first signs of diminished resilience of elderly as compared to young individuals are observed as early as at the age of 45 to 50 after traumatic injuries. Besides several other factors, cellular senescence has been identified as a key driver of aging, age-associated diseases and thus also of diminished resilience. Indeed, eliminating senescent cells in various pre-clinical models of age-associated diseases including osteoarthritis or osteoporosis, but also in cartilage or bone regeneration after traumatic injuries leads to later onset or improvement of the specific conditions.

In order to understand how senescent cells that accumulate within organisms with age negatively impact on organ and tissue function and regeneration, we focus on function of miRNAs (Brenner et al., 2021; Terlecki-Zaniewicz et al., 2019) and proteins differentially regulated in senescent and stressed cells, in tissue culture models (Weinmuellner et al., 2017; Weinmüllner et al., 2020) and their impact on tissue regeneration and organismal aging (Heissenberger et al., 2020, 2019; Schosserer et al., 2015), which also allows for identifying novel senolytic targets and therapeutics. In addition, the pro-inflammatory activity of senescent cells via its senescence associated secretory phenotype (SASP) is considered a prominent driver of the aging process and inhibitor of sufficiently boosting pro-regenerative activity of the endogenous repair mechanisms. Therefore, we focus on SASP factors including lipids (Narzt et al., 2020; Pils et al., 2021) and circulating miRNAs as biomarkers for senescent cell loads in organisms or as diagnostics in age-associated diseases as well as on the pro-inflammatory SASP (Grillari et al., 2020; Hackl et al., 2015; Heilmeier et al., 2022; Morsiani et al., 2021) as a therapeutic target. We are specifically interested in developing extracellular vesicles of MSCs into potential therapeutic strategies for tissue regeneration in young and elderly individuals as a platform technology (Gimona et al., 2021; Vogt et al., 2021, 2018) that will be tested in cooperation with all groups of LBI Trauma, especially in the context of wound healing, as well as in bone, cartilage and neuroregeneration.

Vascular Biology

In most higher organisms, vessels play a fundamental role. They transport blood from the heart throughout the body and drain tissue fluid back into the blood circulation. The cells that line up the inner side of these vessels are called endothelial cells. In the human body they weigh approximately one kilogram and if all vessels are laid end-to-end together they could encompass the earth twice.

The group of Wolfgang Holnthoner focuses on basic functions of endothelial cells in the formation and growth of blood and lymphatic vessels. In tissue regeneration new vessels are expected to sprout so that organs can be supplied with oxygen and nutrients. Further research emphasis is put on:

Isolation of endothelial cells and their progenitor cells (EPC) from peripheral blood and fat tissue
Co-cultures of endothelial cells and mesenchymal stem cells as tools for vascularization for tissue engineering
The role of endothelial cells in blood coagulation
The role of extracellular vesicles such as microparticles and exosomes in vascular biology
The influence of purinergic signaling on endothelial sprouting

The aim is to develop vascularization strategies that can be used in a clinical setting. Central for that is the characterization of artificial vascular structures. Furthermore, the regeneration of existing blood and lymphatic vessels represents a focus of the research in the endothelial cell group.

Nanoparticle-based Therapies

The major research focus is the development of methods for quantitative analysis of biological systems at the nanoscale. Our group has long-time experience in single molecule fluorescence microscopy, force microscopy as well as 2D/3D nanolithography. By precisely localising and measuring the dynamics of biomolecules and determining molecular interactions, we seek to understand their function in model systems as well as in living cells. We are currently engaged in method development for the characterisation and understanding of physical properties of individual cells, nanobioparticles or lipids and proteins. Another important aspect of our work is the application of our research to the development of device technologies and image processing tools.