TY - JOUR A1 - Borojević, Ana A1 - Jauković, Aleksandra A1 - Kukolj, Tamara A1 - Mojsilović, Slavko A1 - Obradović, Hristina A1 - Trivanović, Drenka A1 - Živanović, Milena A1 - Zečević, Željko A1 - Simić, Marija A1 - Gobeljić, Borko A1 - Vujić, Dragana A1 - Bugarski, Diana T1 - Vitamin D3 stimulates proliferation capacity, expression of pluripotency markers, and osteogenesis of human bone marrow mesenchymal stromal/stem cells, partly through SIRT1 signaling JF - Biomolecules N2 - The biology of vitamin D3 is well defined, as are the effects of its active metabolites on various cells, including mesenchymal stromal/stem cells (MSCs). However, the biological potential of its precursor, cholecalciferol (VD3), has not been sufficiently investigated, although its significance in regenerative medicine — mainly in combination with various biomaterial matrices — has been recognized. Given that VD3 preconditioning might also contribute to the improvement of cellular regenerative potential, the aim of this study was to investigate its effects on bone marrow (BM) MSC functions and the signaling pathways involved. For that purpose, the influence of VD3 on BM-MSCs obtained from young human donors was determined via MTT test, flow cytometric analysis, immunocytochemistry, and qRT-PCR. Our results revealed that VD3, following a 5-day treatment, stimulated proliferation, expression of pluripotency markers (NANOG, SOX2, and Oct4), and osteogenic differentiation potential in BM-MSCs, while it reduced their senescence. Moreover, increased sirtuin 1 (SIRT1) expression was detected upon treatment with VD3, which mediated VD3-promoted osteogenesis and, partially, the stemness features through NANOG and SOX2 upregulation. In contrast, the effects of VD3 on proliferation, Oct4 expression, and senescence were SIRT1-independent. Altogether, these data indicate that VD3 has strong potential to modulate BM-MSCs' features, partially through SIRT1 signaling, although the precise mechanisms merit further investigation. KW - bone marrow mesenchymal stromal cells (BM-MSCs) KW - vitamin D3 (cholecalciferol, VD3) KW - SIRT1 KW - regenerative potential KW - stemness KW - osteogenesis Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-262203 SN - 2218-273X VL - 12 IS - 2 ER - TY - JOUR A1 - Trivanović, Drenka T1 - Adult stem cells in aging JF - Journal of Personalized Medicine N2 - No abstract available KW - adult stem cells Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-275226 SN - 2075-4426 VL - 12 IS - 5 ER - TY - JOUR A1 - Pereira, Ana Rita A1 - Trivanović, Drenka A1 - Stahlhut, Philipp A1 - Rudert, Maximilian A1 - Groll, Jürgen A1 - Herrmann, Marietta T1 - Preservation of the naïve features of mesenchymal stromal cells in vitro: Comparison of cell- and bone-derived decellularized extracellular matrix JF - Journal of Tissue Engineering N2 - The fate and behavior of bone marrow mesenchymal stem/stromal cells (BM-MSC) is bidirectionally influenced by their microenvironment, the stem cell niche, where a magnitude of biochemical and physical cues communicate in an extremely orchestrated way. It is known that simplified 2D in vitro systems for BM-MSC culture do not represent their naïve physiological environment. Here, we developed four different 2D cell-based decellularized matrices (dECM) and a 3D decellularized human trabecular-bone scaffold (dBone) to evaluate BM-MSC behavior. The obtained cell-derived matrices provided a reliable tool for cell shape-based analyses of typical features associated with osteogenic differentiation at high-throughput level. On the other hand, exploratory proteomics analysis identified native bone-specific proteins selectively expressed in dBone but not in dECM models. Together with its architectural complexity, the physico-chemical properties of dBone triggered the upregulation of stemness associated genes and niche-related protein expression, proving in vitro conservation of the naïve features of BM-MSC. KW - decellularization KW - bone model KW - stem cell niche KW - stemness KW - osteogenesis KW - 3D models Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-268835 VL - 13 ER - TY - JOUR A1 - Herrmann, Marietta A1 - Diederichs, Solvig A1 - Melnik, Svitlana A1 - Riegger, Jana A1 - Trivanović, Drenka A1 - Li, Shushan A1 - Jenei-Lanzl, Zsuzsa A1 - Brenner, Rolf E. A1 - Huber-Lang, Markus A1 - Zaucke, Frank A1 - Schildberg, Frank A. A1 - Grässel, Susanne T1 - Extracellular Vesicles in Musculoskeletal Pathologies and Regeneration JF - Frontiers in Bioengineering and Biotechnology N2 - The incidence of musculoskeletal diseases is steadily increasing with aging of the population. In the past years, extracellular vesicles (EVs) have gained attention in musculoskeletal research. EVs have been associated with various musculoskeletal pathologies as well as suggested as treatment option. EVs play a pivotal role in communication between cells and their environment. Thereby, the EV cargo is highly dependent on their cellular origin. In this review, we summarize putative mechanisms by which EVs can contribute to musculoskeletal tissue homeostasis, regeneration and disease, in particular matrix remodeling and mineralization, pro-angiogenic effects and immunomodulatory activities. Mesenchymal stromal cells (MSCs) present the most frequently used cell source for EV generation for musculoskeletal applications, and herein we discuss how the MSC phenotype can influence the cargo and thus the regenerative potential of EVs. Induced pluripotent stem cell-derived mesenchymal progenitor cells (iMPs) may overcome current limitations of MSCs, and iMP-derived EVs are discussed as an alternative strategy. In the last part of the article, we focus on therapeutic applications of EVs and discuss both practical considerations for EV production and the current state of EV-based therapies. KW - extracellular vesicles KW - exosomes KW - musculoskeletal diseases KW - MSC KW - iMP KW - cell-free therapeutics Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-222882 SN - 2296-4185 VL - 8 ER -