Thomas Kurth

TU Dresden | TUD · Technology Platform of the Center for Molecular and Cellular Bioengineering

Once human photoreceptors die, they do not regenerate, thus photoreceptor transplantation has emerged as a potential treatment approach for blinding diseases. Improvements in transplant organization, donor cell maturation and synaptic connectivity to the host will be critical in advancing this technology to clinical practice. Unlike the unstructure...

The possible applications for human retinal organoids (HROs) derived from human induced pluripotent stem cells (hiPSC) rely on the robustness and transferability of the methodology for their generation. Standardized strategies and parameters to effectively assess, compare, and optimize organoid protocols are starting to be established, but are not...

The functionality of photoreceptors, rods, and cones is highly dependent on their outer segments (POS), a cellular compartment containing highly organized membranous structures that generate biochemical signals from incident light. While POS formation and degeneration are qualitatively assessed on microscopy images, reliable methodology for quantit...

Primary cilia are sensory organelles present in many cell types, partaking in various signaling processes. Primary cilia of pancreatic beta cells play pivotal roles in paracrine signaling and their dysfunction is linked to diabetes. Yet, the structural basis for their functions is unclear. We present three-dimensional reconstructions of beta cell p...

Blunted first-phase insulin secretion and insulin deficiency are indicators of β cell dysfunction and diabetes manifestation. Therefore, insights into molecular mechanisms that regulate insulin homeostasis might provide entry sites to replenish insulin content and restore β cell function. Here, we identify the insulin inhibitory receptor (inceptor;...

Loss of retinal pigment epithelium (RPE) cells in the eye leads to photoreceptor death and vision loss. Cell replacement strategies using RPE derived in vitro from pluripotent stem cells (PSCs) has emerged as a promising therapeutic strategy. Generation of polarized monolayers represents an essential prerequisite for proper RPE function, however, m...

Zebrafish regenerate their fins which involves a component of cell plasticity. It is currently unclear how regenerate cells divide labor to allow for appropriate growth and patterning. Here, we studied lineage relationships of fluorescence-activated cell sorting-enriched epidermal, bone-forming (osteoblast), and (non-osteoblast) blastemal fin regen...

Primary cilia are sensory organelles present in many cell types. Based on an array of microtubules termed axoneme they form a specialized membrane compartment partaking in various signaling processes. Primary cilia of pancreatic islet beta cells play a role in autocrine and paracrine signaling and are linked to diabetes. Yet, the structural basis f...

Objective The consequences of mutations in genes associated with monogenic forms of diabetes on human pancreas development cannot be studied in a time-resolved fashion in vivo. More specifically, if recessive mutations in the insulin gene influence human pancreatic endocrine lineage formation is still an unresolved question. Methods To model the e...

Embryonic development is orchestrated by the action of morphogens, which spread out from a local source and activate, in a field of target cells, different cellular programs based on their concentration gradient. Fibroblast growth factor 8 (Fgf8) is a morphogen with important functions in embryonic organizing centers. It forms a gradient in the ext...

Spermatogenesis is a crucial biological process that enables the production of functional sperm, allowing for successful reproduction. Proper germ cell differentiation and maturation require tight regulation of hormonal signals, cellular signaling pathways, and cell biological processes. The acrosome is a lysosome-related organelle at the anterior...

Zebrafish faithfully regenerate their fins after amputation which includes restoration of bone tissue and a component of cell plasticity. It is currently unclear how different cell populations of the regenerate divide labor to allow for efficient regenerate growth and proper patterning. Here, we studied lineage relationships of FACS-enriched epider...

Neurodegenerative diseases remain incompletely understood and therapies are needed. Stem cell-derived organoid models facilitate fundamental and translational medicine research. However, to which extent differential neuronal and glial pathologic processes can be reproduced in current systems is still unclear. Here, we tested 16 different chemical,...

Elongation of the posterior body axis is distinct from that of the anterior trunk and head. Early drivers of posterior elongation are the neural plate/tube and notochord, later followed by the presomitic mesoderm (PSM), together with the neural tube and notochord. In axolotl, posterior neural plate-derived PSM is pushed posteriorly by convergence a...

Embryo grafts have been an experimental pillar in developmental biology, and particularly, in amphibian biology. Grafts have been essential in constructing fate maps of different cell populations and migratory patterns. Likewise, autografts and allografts in older larvae or adult salamanders have been widely used to disentangle mechanisms of regene...

Human organoids could facilitate research of complex and currently incurable neuropathologies, such as age-related macular degeneration (AMD) which causes blindness. Here, we establish a human retinal organoid system reproducing several parameters of the human retina, including some within the macula, to model a complex combination of photoreceptor...

Cell transplantation is a promising therapeutic approach to recover loss of neurons and vision in patient retinas. So far, human photoreceptor transplants restored some visual function in degenerating mouse retina. Whether retinal cell transplants also integrate into human retina, and how to optimize this for different pathologies are still unknown...

Freshwater grazers are suitable organisms to investigate the fate of environmental pollutants, such as weathered multi-walled carbon nanotubes (wMWCNTs). One key process is the uptake of ingested materials into digestive or absorptive cells. To address this, we investigated the localization of wMWCNTs in the intestinal tracts of the mud snail Lymna...

Although the development and application of nanomaterials is a growing industry, little data is available on the ecotoxicological effects on aquatic organisms. Therefore, we set up a workflow to address the potential uptake of weathered multi-walled carbon nanotubes (wMWCNTs) by a model organism, the pulmonary mud snail Lymnaea stagnalis ( L. stagn...

In T cells, processes such as migration and immunological synapse formation are accompanied by the dynamic reorganization of the actin cytoskeleton, which has been suggested to be mediated by regulators of RhoGTPases and by F-actin bundlers. SWAP-70 controls F-actin dynamics in various immune cells, but its role in T cell development and function h...

The functional contribution of transient receptor potential vanilloid 4 (TRPV4) expression in maintaining human corneal endothelial cells (HCEC) homeostasis is unclear. Accordingly, we determined the effects of TRPV4 gene and protein overexpression on responses modulating the viability and survival of HCEC. Q‑PCR, Western blot, FACS analyses and fl...

Stem cell bioengineering and therapy require different model systems and materials in different stages of development. If a chemically defined biomatrix system can fulfill most tasks, it can minimize the discrepancy among various setups. By screening biomaterials synthesized through a coacervation‐mediated self‐assembling mechanism, a biomatrix sys...

Prostate cancer (PCa) is the most frequent malignancy in older men with a high propensity for bone metastases. Characteristically, PCa causes osteosclerotic lesions as a result of disrupted bone remodeling. Extracellular vesicles (EVs) participate in PCa progression by conditioning the pre-metastatic niche. However, how EVs mediate the cross-talk b...

Regeneration-competent species possess the ability to reverse the progression of severe diseases by restoring the function of the damaged tissue. However, the cellular dynamics underlying this capability remain unexplored. Here, we have used single-cell transcriptomics to map de novo β-cell regeneration during induction and recovery from diabetes i...

In-depth characterization has introduced new molecular subtypes of gastric cancer (GC). To identify these, new approaches and techniques are required. Liquid biopsies are trendsetting and provide an easy and feasible method to identify and to monitor GC patients. In a prospective cohort of 87 GC patients, extracellular vesicles (EVs) were isolated...

Inflammatory bowel disease (IBD) is characterized by inappropriate immune responses to the microbiota in genetically susceptible hosts, but little is known about the pathways that link individual genetic alterations to microbiota-dependent inflammation. Here, we demonstrated that the loss of X-linked inhibitor of apoptosis protein (XIAP), a gene as...

Significance The failure of β cells to secrete sufficient amounts of insulin is a key feature of diabetes mellitus. Each β cell secretes only a small amount of insulin upon stimulation in a highly regulated fashion: young insulin is preferentially released, whereas old insulin is mainly degraded within the β cell. How this process is regulated in v...

Once human photoreceptors die, they do not regenerate, thus photoreceptor transplantation has emerged as a potential treatment approach for blinding diseases. Improvements in transplant organization, donor cell maturation and synaptic connectivity to the host will be critical in advancing this technology to clinical practice. Unlike the unstructure...

Regeneration-competent species possess the ability to reverse the progression of severe diseases by restoring the function of the damaged tissue. However, the cellular dynamics underlying this capability remain unexplored. Here, we use single-cell transcriptomics to map the cellular dynamics underlying de novo β-cell regeneration during induction a...

Although the development and application of nanomaterials is a growing industry, little data is available on the ecotoxicological effects on aquatic organisms. Therefore, we set up a workflow to address the potential uptake of weathered multi-walled carbon nanotubes (wMWCNTs) by a model organism, the pulmonary mudsnail Lymnaea stagnalis (L. stagnal...

Using retinal organoid systems, organ-like 3D tissues, relies implicitly on their robustness. However, essential key parameters, particularly retinal growth and longer-term culture, are still insufficiently defined. Here, we hypothesize that a previously optimized protocol for high yield of evenly-sized mouse retinal organoids with low variability...

β-cells produce, store and secrete insulin upon elevated blood glucose levels. Insulin secretion is a highly regulated process. The probability for insulin secretory granules to undergo fusion with the plasma membrane or being degraded is correlated with their age. However, the molecular features and stimuli connected to this behavior have not yet...

Many features of extracellular matrices, e.g., self-healing, adhesiveness, viscoelasticity, and conductivity, are associated with the intricate networks composed of many different covalent and non-covalent chemical bonds. Whereas a reductionism approach would have the limitation to fully recapitulate various biological properties with simple chemic...

Microtubules play a major role in intracellular trafficking of vesicles in endocrine cells. Detailed knowledge of microtubule organization and their relation to other cell constituents is crucial for understanding cell function. However, their role in insulin transport and secretion is under debate. Here, we use FIB-SEM to image islet β cells in th...

Spinal cord injury (SCI) results in loss of neurons, oligodendrocytes and myelin sheaths, all of which are not efficiently restored. The scarcity of oligodendrocytes in the lesion site impairs remyelination of spared fibres, which leaves axons denuded, impedes signal transduction and contributes to permanent functional deficits. In contrast to mamm...

Microtubules play a major role in intracellular trafficking of cargo vesicles in endocrine cells and detailed knowledge of the microtubule network organization and its relation to other cell constituents is crucial for understanding primary cell function. However, their role in insulin transport and secretion is currently under debate. Here, we use...

Changes in axonal myelination are an important hallmark of aging and a number of neurological diseases. De- myelinated axons are impaired in their function and degenerate over time. Oligodendrocytes, the cells responsible for myelination of axons, are sensitive to mechanical properties of their environment. Growing evidence indi- cates that mechani...

Mutations in cis-regulatory elements play important roles for phenotypic changes during evolution. Eye degeneration in the blind mole rat (BMR; Nannospalax galili) and other subterranean mammals is significantly associated with widespread divergence of eye regulatory elements, but the effect of these regulatory mutations on eye development and func...

Extracellular membrane vesicles (EVs) are emerging as new vehicles in intercellular communication, but how the biological information contained in EVs is shared between cells remains elusive. Several mechanisms have been described to explain their release from donor cells and the initial step of their uptake by recipient cells, which triggers a cel...

Coccidian parasites possess complex life cycles involving asexual proliferation followed by sexual development leading to the production of oocysts. Coccidian oocysts are persistent stages which are secreted by the feces and transmitted from host to host guaranteeing life cycle progression and disease transmission. The robust bilayered oocyst wall...

Objective The intestinal epithelium is a rapidly renewing tissue which plays central roles in nutrient uptake, barrier function and the prevention of intestinal inflammation. Control of epithelial differentiation is essential to these processes and is dependent on cell type-specific activity of transcription factors which bind to accessible chromat...

Pancreatic islet beta cells employ secretory granules for the storage and glucose-stimulated release of the hormone insulin. The competence of an insulin granule for exocytosis depends on spatial and temporal variables such as its proximity to the plasma membrane as well as its age, with newly-generated granules being preferentially released. The m...

Mutations in cis-regulatory elements play important roles for phenotypic changes during evolution. Eye degeneration in subterranean mammals is associated with divergence of eye regulatory elements. Here, we investigate the effect of mutations observed in the blind mole rat (BMR) sequence of a conserved non-coding element upstream of Tdrd7, a gene r...

Maintenance of a healthy photoreceptor-retinal pigment epithelium (RPE) interface is essential for vision. At the center of this interface, apical membrane protrusions stemming from the RPE ensheath photoreceptor outer segments (POS), and are possibly involved in the recycling of POS through phagocytosis. The molecules that regulate POS ensheathmen...

Severe injury to the mammalian spinal cord results in permanent loss of function due to the formation of a glial-fibrotic scar. Both the chemical composition and the mechanical properties of the scar tissue have been implicated to inhibit neuronal regrowth and functional recovery. By contrast, adult zebrafish are able to repair spinal cord tissue a...

Significance Cells maintain several mechanisms to ensure their survival, including the removal of old or damaged proteins and organelles. This process must be balanced: too little turnover results in the accumulation of cellular “junk,” while excessive removal can deplete the cell and organism of key components. Here, we show that Atp6ap2 in the pa...

In article number 1900128, Anna V. Taubenberger and co‐workers employ fluorescently labelled polyacrylamide beads (Cy3, green) as stress sensors that are incorporated into hydrogels together with breast cancer cells. After 14 days, tumor spheroid cultures were fixed, stained for F‐actin (red) and nuclei (blue), and imaged via confocal microscopy (m...

The mechanical properties of cancer cells and their microenvironment contribute to breast cancer progression. While mechanosensing has been extensively studied using 2D substrates, much less is known about it in a physiologically more relevant 3D context. Here it is demonstrated that breast cancer tumor spheroids, growing in 3D polyethylene glycol‐...

Severe injury to the mammalian spinal cord results in permanent loss of function due to the formation of a glial-fibrotic scar. Both the chemical composition and the mechanical properties of the scar tissue have been implicated to inhibit neuronal regrowth and functional recovery. By contrast, adult zebrafish are able to repair spinal cord tissue a...

Mechanical properties of cancer cells and their microenvironment contribute to breast cancer progression. While mechanosensing has been extensively studied using two-dimensional (2D) substrates, much less is known about it in a physiologically more relevant 3D context. Here we demonstrate that breast cancer tumor spheroids, growing in 3D polyethyle...

The introduction of stem cell-based technologies for the derivation of three-dimensional retinal tissues, the so-called retinal organoids, offers many new possibilities for vision research: Organoids facilitate studies on retinal development and in vitro retinal disease modeling, as well as being valuable for drug testing. Further, retinal organoid...

The alteration or decrease of axonal myelination is an important hallmark of aging and disease. Demyelinated axons are impaired in their function and degenerate over time. Oligodendrocytes, the cells responsible for myelination of axons, are sensitive to mechanical properties of their environment. Growing evidence indicates that mechanical properti...

Full-text accessible via this link: https://rdcu.be/6H94 Honey bee (Apis spp.) royal jelly, a glandular secretion used to raise young larvae to future queens, has long been considered merely as food. Since queen larvae are raised upside down in their vertically oriented queen cells, royal jelly also needs to adhere the larvae to the cell ceiling to...

The endocytic pathway plays an instrumental role in recycling internalized molecules back to the plasma membrane or to direct them to lysosomes for degradation. We recently reported a new role of endosomes - the delivery of components from extracellular vesicles (EVs) to the nucleoplasm of recipient cells. Using indirect immunofluorescence, fluores...

Neural stem cells (NSCs) constitute an endogenous reservoir for neurons that could potentially be harnessed for regenerative therapies in disease contexts such as neurodegeneration. However, in Alzheimer's disease (AD), NSCs lose plasticity and thus possible regenerative capacity. We investigate how NSCs lose their plasticity in AD by using starPEG...