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1.
PLoS One ; 19(3): e0294497, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38527018

RESUMEN

Previous research has shown that perceived existential threat experienced during or shortly after the first wave of the global COVID-19 pandemic, engendered anticipated scarcity and stockpiling behavior. However, the relationship between anticipated scarcity and stockpiling may not hold unambiguously for everyone. Across two studies and one preregistered replication (N = 644), we show that perceived threat of COVID-19 is associated with stockpiling tendencies by increasing the anticipation of product scarcity-a resource threat. The association between anticipated product scarcity and stockpiling depends, however, on childhood socio-economic status (SES) and materialism. For individuals with low childhood SES, the anticipation of product scarcity was only associated with stockpiling among those who valued materialism. Individuals with high childhood SES, by contrast, stockpiled in response to anticipated scarcity regardless of their level of materialism. Our findings qualify previous literature on the association between perceived threat of COVID-19, anticipated scarcity and stockpiling during the COVID-19 pandemic and help reconcile contradictory predictions about the role of childhood SES in individuals' consumption behavior in response to adversity.


Asunto(s)
COVID-19 , Humanos , COVID-19/epidemiología , Pandemias , Clase Social
2.
Front Bioeng Biotechnol ; 10: 860138, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35782512

RESUMEN

Stem cell-derived kidney organoids have been shown to self-organize from induced pluripotent stem cells into most important renal structures. However, the structures remain immature in culture and contain endothelial networks with low connectivity and limited organoid invasion. Furthermore, the nephrons lose their phenotype after approximately 25 days. To become applicable for future transplantation, further maturation in vitro is essential. Since kidneys in vivo develop in hypoxia, we studied the modulation of oxygen availability in culture. We hypothesized that introducing long-term culture at physiological hypoxia, rather than the normally applied non-physiological, hyperoxic 21% O2, could initiate angiogenesis, lead to enhanced growth factor expression and improve the endothelial patterning. We therefore cultured the kidney organoids at 7% O2 instead of 21% O2 for up to 25 days and evaluated nephrogenesis, growth factor expression such as VEGF-A and vascularization. Whole mount imaging revealed a homogenous morphology of the endothelial network with enhanced sprouting and interconnectivity when the kidney organoids were cultured in hypoxia. Three-dimensional vessel quantification confirmed that the hypoxic culture led to an increased average vessel length, likely due to the observed upregulation of VEGFA-189 and VEGFA-121, and downregulation of the antiangiogenic protein VEGF-A165b measured in hypoxia. This research indicates the importance of optimization of oxygen availability in organoid systems and the potential of hypoxic culture conditions in improving the vascularization of organoids.

3.
Adv Sci (Weinh) ; 9(20): e2200543, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35567354

RESUMEN

Pluripotent stem cell-derived kidney organoids offer a promising solution to renal failure, yet current organoid protocols often lead to off-target cells and phenotypic alterations, preventing maturity. Here, various dynamic hydrogel architectures are created, conferring a controlled and biomimetic environment for organoid encapsulation. How hydrogel stiffness and stress relaxation affect renal phenotype and undesired fibrotic markers are investigated. The authors observe that stiff hydrogel encapsulation leads to an absence of certain renal cell types and signs of an epithelial-mesenchymal transition (EMT), whereas encapsulation in soft, stress-relaxing hydrogels leads to all major renal segments, fewer fibrosis or EMT associated proteins, apical proximal tubule polarization, and primary cilia formation, representing a significant improvement over current approaches to culture kidney organoids. The findings show that engineering hydrogel mechanics and dynamics have a decided benefit for organoid culture. These structure-property-function relationships can enable the rational design of materials, bringing us closer to functional engraftments and disease-modeling applications.


Asunto(s)
Organoides , Células Madre Pluripotentes , Transición Epitelial-Mesenquimal , Hidrogeles , Riñón
4.
Open Res Eur ; 2: 87, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-37645341

RESUMEN

Microscopy has revolutionised our view on biology and has been vital for many discoveries since its invention around 200 years ago. Recent developments in cell biology have led to a strong interest in generating spheroids and organoids that better represent tissue. However, the current challenge faced by many researchers is the culture and analysis of these three-dimensional (3D) cell cultures. With the technological improvements in reconstructing volumetric datasets by optical sections, it is possible to quantify cells, their spatial arrangement, and the protein distribution without destroying the physical organization. We assessed three different microwell culture plates and four analysis tools for 3D imaging data for their applicability for the analysis of 3D cultures. A key advantage of microwell plates is their potential to perform high-throughput experiments in which cell cultures are generated and analysed in one single system. However, it was shown that this potential could be impacted by the material composition and microwell structure. For example, antibody staining was not possible in a hydrogel microwell, and truncated pyramid-structured microwells had increased background fluorescence due to their structure. Regarding analysis tools, four different software, namely CellProfiler, Fiji/ImageJ, Nikon GA3 and Imaris, were compared for their accuracy and applicability in analysing datasets from 3D cultures. The results showed that the open-access software, CellProfiler and Fiji, could quantify nuclei and cells, yet with varying results compared to manual counting, and may require post-processing optimisation. On the other hand, the GA3 and Imaris software packages showed excellent versatility in usage and accuracy in the quantification of nuclei and cells, and could classify cell localisation. Together these results provide critical considerations for microscopic imaging and analysis of 3D cell cultures.

5.
Biomaterials ; 275: 120976, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-34198162

RESUMEN

Differentiated kidney organoids from induced pluripotent stem cells hold promise as a treatment for patients with kidney diseases. Before these organoids can be translated to the clinic, shortcomings regarding their cellular and extracellular compositions, and their developmental plateau need to be overcome. We performed a proteomic analysis on kidney organoids cultured for a prolonged culture time and we found a specific change in the extracellular matrix composition with increased expression of types 1a1, 2 and 6a1 collagen. Such an excessive accumulation of specific collagen types is a hallmark of renal fibrosis that causes a life-threatening pathological condition by compromising key functions of the human kidney. Here we hypothesized the need for a three-dimensional environment to grow the kidney organoids, which could better mimic the in vivo surroundings of the developing kidney than standard culture on an air-liquid interface. Encapsulating organoids for four days in a soft, thiol-ene cross-linked alginate hydrogel resulted in decreased type 1a1 collagen expression. Furthermore, the encapsulation did not result in any changes of organoid structural morphology. Using a biomaterial to modulate collagen expression allows for a prolonged kidney organoid culture in vitro and a reduction of abnormal type 1a1 collagen expression bringing kidney organoids closer to clinical application.


Asunto(s)
Colágeno Tipo I/metabolismo , Matriz Extracelular , Hidrogeles , Organoides , Alginatos , Cadena alfa 1 del Colágeno Tipo I , Humanos , Riñón , Proteómica , Compuestos de Sulfhidrilo
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