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Biology subjects

Baur, A. S.

Publications and source records attributed to Baur, A. S..

3 recordsLinked to original sources

Single-cell dissection of urine-derived stem cell hierarchies reveals robust chondrogenesis and clinical scalability

Developing of models of human cartilage and bone growth is essential for the study of growth disorders and to advance towards personalized therapeutic interventions. The majority of in vitro strategies depend on the use of invasively obtained mesenchymal stem cells (MSCs) or the laborious generation of induced pluripotent stem cells (iPSCs). We have now established urine-derived stem cells (USCs) as a non-invasive stem cell source capable of osteogenic and robust chondrogenic spheroid differentiation. Single-cell RNA sequencing of USCs revealed a hierarchy originating from parietal epithelial cells of the kidney, with a proliferative TOP2A subpopulation governed by MYC and E2F4 regulatory networks. Pseudo-time analysis of chondrogenic USCs uncovered alternative chondrogenic differentiation trajectories with an ALDH1A2 intermediate state and a TIMP3-expressing chondrocyte-like subpopulation as the major endpoint, exhibiting cartilage-specific gene ontologies. In conclusion, a streamlined, xeno-free culture and differentiation protocol was developed, thereby establishing the basis for clinical-grade cell expansion and cartilage matrix formation. This positions USCs as a powerful tool for studying cartilage biology and a potential platform for development and use in regenerative therapies.

genetics↗

Interferometric nanoparticle tracking analysis enables label-free discrimination of extracellular vesicles from large lipoproteins

Extracellular vesicles (EVs) are increasingly gaining interest as biomarkers and therapeutics. Accurate sizing and quantification of EVs remain problematic, given their nanometer size range and small scattering cross-sections. This is compounded by the fact that common EV isolation methods result in co-isolation of particles with comparable features. Especially in blood plasma, similarly-sized lipoproteins outnumber EVs to a great extent. Recently, interferometric nanoparticle tracking analysis (iNTA) was introduced as a particle analysis method that enables determining the size and refractive index of nanoparticles with high sensitivity and precision. In this work, we apply iNTA to differentiate between EVs and lipoproteins, and compare its performance to conventional nanoparticle tracking analysis (NTA). We show that iNTA can accurately quantify EVs in artificial EV-lipoprotein mixtures and in plasma-derived EV samples of varying complexity. Conventional NTA could not report on EV numbers, as it was not able to distinguish between EVs and lipoproteins. iNTA has the potential to become a new standard for label-free EV characterization in suspension.

biophysics↗

Liver cells and PBMC secrete Tumor-suppressive Plasma Extracellular Vesicles in Melanoma patients

Before and after surgery melanoma patients harbor elevated levels of extracellular vesicles in plasma (pEV), but their cellular origin is obscure. Here we suggest that these pEV are secreted in part by tumor cells, but particularly by liver and peripheral blood mononuclear cells (PBMC), which strongly suppressed tumor cell activity. As the cellular origin of pEV is difficult to determine, we mimicked the interaction of tumor cells with liver cells and PBMC in vitro, and compared newly secreted EV-associated miRNAs and protein factors with those detected in melanoma patients pEV. The results identified factors that could be associated either with tumor cell activity or the counteracting immune system and liver cells. Notably, the presence/absence of these factors correlated with the clinical stage and tumor relapse. Our study provides new insights into the innate immune defense against tumor cells and implies that residual tumor cells may be more active than previously thought.\n\nSummary blurbPlasma extracellular vesicles (pEV) in melanoma patients are a mix of cancer cell-suppressive vesicles from liver cells and PBMC, but derive also from residual cancer cells.

cancer biology↗