Biology subjects

Osch, G. v.

Publications and source records attributed to Osch, G. v..

3 recordsLinked to original sources

bioRxiv2023

Senescence during early differentiation reduced the chondrogenic differentiation capacity of mesenchymal progenitor cells

Mesenchymal stromal/progenitor cells (MSCs) are promising for cartilage cell-based therapies due to their differentiation capacity. However, MSCs can become senescent during in vitro expansion, a state characterized by stable cell cycle arrest, metabolic alterations, and substantial changes in the gene expression and secretory profile of the cell. In this study, we aimed to investigate how senescence and the senescence associated secretory phenotype (SASP) affect chondrogenic differentiation of MSCs. To study the effect of senescence, we exposed MSCs to gamma irradiation during expansion or during chondrogenic differentiation (pellet culture). When senescence was induced during expansion or at day-7 of chondrogenic differentiation, we observed a significant reduction in cartilage matrix. Interestingly, when senescence was induced at day-14 of differentiation, chondrogenesis was not significantly altered. Moreover, exposing chondrogenic pellets to medium conditioned by senescent pellets had no significant effect on the expression of anabolic or catabolic cartilage markers, suggesting a neglectable paracrine effect of senescence on cartilage generation in our model. Finally, we show that senescent MSCs had lower phosphorylated SMAD2 levels after TGF{beta}1stimulation compared to control MSCs. Overall, these results suggest that the occurrence of senescence in MSCs during expansion or early differentiation could be detrimental for cartilage tissue engineering.

bioengineering↗

bioRxiv2023

Rational positioning of 3D printed micro-bricks to realize high-fidelity, multi-functional soft-hard interfaces

AO_SCPLOWBSTRACTC_SCPLOWLiving organisms have developed design principles, such as functional gradients (FGs), to interface hard materials with soft ones (e.g., bone and tendon). Mimicking such design principles can address the challenges faced when developing engineered constructs with soft-hard interfaces. To date, implementing these FG design principles has been primarily performed by varying the ratio of the hard phase to that of the soft phase. Such design approaches, however, lead to inaccurate mechanical properties within the transition zone. That is due to the highly nonlinear relationship between the material distribution at the microscale and the macroscale mechanical properties. Here, we 3D print micro-bricks from either a soft or a hard phase and study the nonlinear relationship between their arrangements within the transition zone and the resulting macroscale properties. We carry out experiments at the micro- and macroscales as well as finite element simulations at both scales. Based on the obtained results, we develop a co-continuous power-law model relating the arrangement of the micro-bricks to the local mechanical properties of the micro-brick composites. We then use this model to rationally design FGs at the individual micro-brick level and create two types of biomimetic soft-hard constructs, including a specimen modeling bone-ligament junctions in the knee and another modeling the nucleus pulposus-annulus fibrosus interface in intervertebral discs. We show that the implemented FGs drastically enhance the stiffness, strength, and toughness of both types of specimens as compared to non-graded designs. Furthermore, we hypothesize that our soft-hard FGs regulate the behavior of murine preosteoblasts and primary human bone marrow-derived mesenchymal stromal cells (hBMSCc). We culture those cells to confirm the effects of soft-hard interfaces on cell morphology as well as on regulating the expression of focal adhesion kinase, subcellular localization, and YAP nuclear translocation of hBMSCs. Taken together, our results pave the way for the rational design of soft-hard interfaces at the micro-brick level and (biomedical) applications of such designs.

bioengineering↗

bioRxiv2020

TWIST1 controls cellular senescence and energy metabolism in mesenchymal stem cells

Mesenchymal stem cells (MSC) are promising cells for regenerative medicine therapies, because they can differentiate towards multiple cell lineages. However, heterogeneity in differentiation capacity is one of the main drawbacks that limit their use clinically. Differences in the occurrence of cellular senescence and in the expression of the senescence associated secretory phenotype (SASP) in MSC populations contribute to their heterogeneity. Here, we show the involvement of TWIST1 expression in the regulation of MSC senescence, demonstrating that silencing of TWIST1 in MSCs increased the occurrence of senescence. These senescent MSCs had a SASP that was different from irradiation-induced senescent MSCs. In addition, metabolic evaluation performed by the Seahorse XF apparatus showed that both TWIST1 silencing-induced and irradiation-induced senescent MSCs had a higher oxygen consumption compared to control MSCs, while TWIST1 silencing-induced senescent MSCs had a low extracellular acidification rate compared to the irradiation-induced senescent MSCs. Overall, our data indicate how TWIST1 regulation influences senescence in human MSCs and that TWIST1 silencing-induced senescence is characterized by a specific expression of the SASP and the metabolic state.

cell biology↗