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.
Messner Z, Carro-Vazquez D, Haschka J, Grillari J, Resch H, Muschitz C, Pietschmann P, Zwerina J, Hackl M, Kocijan R (2022). Circulating miRNAs Respond to Denosumab Treatment after Two Years in Postmenopausal Women with Osteoporosis. J Clin Endocrinol Metab. 2022 Nov 19:dgac667.
Schanda JE, Heher P, Weigl M, Drechsler S, Schädl B, Prueller J, Kocijan R, Heuberer PR, Hackl M, Muschitz C, Grillari J, Redl H, Feichtinger X, Fialka C, Mittermayr R (2022). Muscle-Specific Micro-Ribonucleic Acids miR-1-3p, miR-133a-3p, and miR-133b Reflect Muscle Regeneration After Single-Dose Zoledronic Acid Following Rotator Cuff Repair in a Rodent Chronic Defect Model. Am J Sports Med. 2022 Oct;50(12):3355-3367.
Carro Vázquez D, Emini L, Rauner M, Hofbauer C, Grillari J, Diendorfer AB, Eastell R, Hofbauer LC, Hackl M (2022) Effect of Anti-Osteoporotic Treatments on Circulating and Bone MicroRNA Patterns in Osteopenic ZDF Rats. Int J Mol Sci. 2022 Jun 10;23(12):6534.
Muschitz C, Hummer M, Grillari J, Hlava A, Birnger AH, Hemetsberger M, Bimai HP (2022) Epidemiology and economic burden of fragility fractures in Austria. Osteoporos Int 2022. Mar;33(3):637-647.
Zupan J, Strazar K, Kocijan R, Nau T, Grillari J, Marolt Presen D (2021) Age-related alterations and senescence of mesenchymal stromal cells: Implications for regenerative treatments of bones and joints. Mech Ageing Dev 2021 Sep;198:111539.
Vogt S, Bobbili MR, Stadlmayr G, Stadlbauer K, Kjems J, Rüker F, Grillari J, Wozniak-Knopp (2021). An engineered CD81-based combinatorial library for selecting recombinant binders to cell surface proteins: Laminin binding CD81 enhances cellular uptake of extracellular vesicles. J Extracell Vesicles. 2021 Sep;10(11):e12139.
Pils V, . 2021 Sep;198:111527.The role of lipid-based signalling in wound healing and senescence. Mech Ageing Dev
Kocijan R, Weigl M, Skalicky S, Geiger E, Ferguson J, Leinfellner G, Heimel P, Pietschmann P, Grillari J, Redl H, Hackl M (2020) MicroRNA levels in bone and blood change during bisphosphonate and teriparatide therapy in an animal model of postmenopausal osteoporosis. Bone. 2020 Feb;131:115104.