@article{AshmwePosaRuehrnoessletal., author = {Ashmwe, Mohamed and Posa, Katja and R{\"u}hrn{\"o}ßl, Alexander and Heinzel, Johannes Christoph and Heimel, Patrick and Mock, Michael and Sch{\"a}dl, Barbara and Keibl, Claudia and Couillard-Despres, Sebastien and Redl, Heinz and Mittermayr, Rainer and Hercher, David}, title = {Effects of Extracorporeal Shockwave Therapy on Functional Recovery and Circulating miR-375 and miR-382-5p after Subacute and Chronic Spinal Cord Contusion Injury in Rats}, series = {Biomedicines}, volume = {2022}, journal = {Biomedicines}, number = {10(7)}, doi = {https://doi.org/10.3390/biomedicines10071630}, pages = {1630}, abstract = {Extracorporeal shockwave therapy (ESWT) can stimulate processes to promote regeneration, including cell proliferation and modulation of inflammation. Specific miRNA expression panels have been established to define correlations with regulatory targets within these pathways. This study aims to investigate the influence of low-energy ESWT-applied within the subacute and chronic phase of SCI (spinal cord injury) on recovery in a rat spinal cord contusion model. Outcomes were evaluated by gait analysis, µCT and histological analysis of spinal cords. A panel of serum-derived miRNAs after SCI and after ESWT was investigated to identify injury-, regeneration- and treatment-associated expression patterns. Rats receiving ESWT showed significant improvement in motor function in both a subacute and a chronic experimental setting. This effect was not reflected in changes in morphology, µCT-parameters or histological markers after ESWT. Expression analysis of various miRNAs, however, revealed changes after SCI and ESWT, with increased miR-375, indicating a neuroprotective effect, and decreased miR-382-5p potentially improving neuroplasticity via its regulatory involvement with BDNF. We were able to demonstrate a functional improvement of ESWT-treated animals after SCI in a subacute and chronic setting. Furthermore, the identification of miR-375 and miR-382-5p could potentially provide new targets for therapeutic intervention in future studies.}, subject = {Tissue Engineering}, language = {en} } @article{BernhardMaroltPresenLietal., author = {Bernhard, Jonathan C and Marolt Presen, Darja and Li, Ming and Monforte, Xavier and Ferguson, James and Leinfellner, Gabriele and Heimel, Patrick and Betti, Susanne L and Shu, Sharon and Teuschl-Woller, Andreas H and Tangl, Stefan and Redl, Heinz and Vunjak-Novakovic, Gordana}, title = {Effects of Endochondral and Intramembranous Ossification Pathways on Bone Tissue Formation and Vascularization in Human Tissue-Engineered Grafts}, series = {Cells}, volume = {11}, journal = {Cells}, number = {19:3070}, doi = {10.3390/cells11193070}, abstract = {Bone grafts can be engineered by differentiating human mesenchymal stromal cells (MSCs) via the endochondral and intramembranous ossification pathways. We evaluated the effects of each pathway on the properties of engineered bone grafts and their capacity to drive bone regeneration. Bone-marrow-derived MSCs were differentiated on silk scaffolds into either hypertrophic chondrocytes (hyper) or osteoblasts (osteo) over 5 weeks of in vitro cultivation, and were implanted subcutaneously for 12 weeks. The pathways' constructs were evaluated over time with respect to gene expression, composition, histomorphology, microstructure, vascularization and biomechanics. Hypertrophic chondrocytes expressed higher levels of osteogenic genes and deposited significantly more bone mineral and proteins than the osteoblasts. Before implantation, the mineral in the hyper group was less mature than that in the osteo group. Following 12 weeks of implantation, the hyper group had increased mineral density but a similar overall mineral composition compared with the osteo group. The hyper group also displayed significantly more blood vessel infiltration than the osteo group. Both groups contained M2 macrophages, indicating bone regeneration. These data suggest that, similar to the body's repair processes, endochondral pathway might be more advantageous when regenerating large defects, whereas intramembranous ossification could be utilized to guide the tissue formation pattern with a scaffold architecture.}, subject = {bone tissue engineering}, language = {en} } @article{RomanelliBielerHeimeletal., author = {Romanelli, Pasquale and Bieler, Lara and Heimel, Patrick and Škokić, Siniša and Jakubecova, Dominika and Kreutzer, Christina and Zaunmair, Pia and Smolčić, Tomislav and Benedetti, Bruno and Rohde, Eva and Gimona, Mario and Hercher, David and Dobrivojević Radmilović, Marina and Couillard-Despres, Sebastien}, title = {Enhancing Functional Recovery Through Intralesional Application of Extracellular Vesicles in a Rat Model of Traumatic Spinal Cord Injury}, series = {Front Cell Neurosci}, volume = {15}, journal = {Front Cell Neurosci}, doi = {10.3389/fncel.2021.795008}, abstract = {Local inflammation plays a pivotal role in the process of secondary damage after spinal cord injury. We recently reported that acute intravenous application of extracellular vesicles (EVs) secreted by human umbilical cord mesenchymal stromal cells dampens the induction of inflammatory processes following traumatic spinal cord injury. However, systemic application of EVs is associated with delayed delivery to the site of injury and the necessity for high doses to reach therapeutic levels locally. To resolve these two constraints, we injected EVs directly at the lesion site acutely after spinal cord injury. We report here that intralesional application of EVs resulted in a more robust improvement of motor recovery, assessed with the BBB score and sub-score, as compared to the intravenous delivery. Moreover, the intralesional application was more potent in reducing inflammation and scarring after spinal cord injury than intravenous administration. Hence, the development of EV-based therapy for spinal cord injury should aim at an early application of vesicles close to the lesion.}, subject = {exosomes}, language = {en} } @article{FeichtingerHeimelTangletal., author = {Feichtinger, Xaver and Heimel, Patrick and Tangl, Stefan and Keibl, Claudia and N{\"u}rnberger, Sylvia and Schanda, Jakob Emanuel and Hercher, David and Kocijan, Roland and Redl, Heinz and Grillari, Johannes and Fialka, Christian and Mittermayr, Rainer}, title = {Improved biomechanics in experimental chronic rotator cuff repair after shockwaves is not reflected by bone microarchitecture}, series = {PLoS One}, volume = {17}, journal = {PLoS One}, number = {1}, doi = {10.1371/journal.pone.0262294}, subject = {chronic rotator cuff repair}, language = {en} }