Biology subjects

Grunewald, M.

Publications and source records attributed to Grunewald, M..

3 recordsLinked to original sources

bioRxiv2024

Immortalized Intestinal Telocytes - A Stem Cell Niche In Vitro

Telocytes, a distinct type of mesenchymal cell, have recently emerged as crucial components of the intestinal stem cell niche, primarily by providing essential Wnt proteins that drive stem cell function. However, their detailed biology and the specific mechanisms by which they regulate stem cell activity remain largely unexplored. Here, we established an immortalized intestinal telocyte cell line that retains the key cellular and molecular characteristics of native telocytes. Remarkably, this cell line, unlike telocyte-depleted immortalized mesenchyme, supports the growth of both mouse and human organoids in co-culture without the need for external factor supplementation. These findings indicate that telocytes are not only essential but are also sufficient to maintain stem cell activity. This immortalized telocyte line provides a valuable source of factors that support stem cell activity in vitro, offering a powerful tool for advancing our understanding of telocyte biology and the reciprocal communication between stem cells and their niche.

cell biology↗

bioRxiv2024

AVJ16 inhibits the RNA binding protein IGF2BP1 in lung adenocarcinomas and prevents tumor growth in mice

IGF2BP1 is an oncofoetal RNA binding protein that is expressed in many tumors. We have recently described a small molecule inhibitor of IGF2BP1, termed AVJ16, that prevents binding of the protein to its RNA targets by directly associating with the protein. Here, using a multi-omics approach, we have analyzed the effects of this inhibition on RNA binding, RNA expression, and protein expression. AVJ16 treatment downregulates RNAs encoding members of several pro-oncogenic signaling pathways, including Hedgehog, Wnt, and PI3K-Akt, and there is a strong correlation between IGF2BP1 RNA binding, RNA expression, and protein expression. AVJ16 treatment of lung adenocarcinoma (LUAD) cells in culture causes a strong reduction in proliferation, colony formation, invasion, and spheroid growth while enhancing apoptosis and cell death. All of these effects are limited to cells expressing IGF2BP1. LUAD cells treated with AVJ16 show a pronounced reduction in vital dye efflux, often correlated with enhanced chemosensitivity. In syngeneic LUAD xenografts in mice, IP injection of AVJ16 prevents tumor growth, and incubation with AVJ16 induces cell death in human organoids derived from IGF2BP1-expressing LUADs but not from healthy lung tissue. These results suggest that AVJ16 is a promising candidate for mono- and/or adjuvant therapy directed against tumors expressing IGF2BP1.

cancer biology↗

bioRxiv2023

MicroCT-based imaging of microvasculature within the bone tissue

Angiogenesis is essential for skeletal development, bone healing, and regeneration. Improved non-destructive, three-dimensional (3D) imaging of the vasculature within bone tissue benefits many research areas, especially implantology and tissue engineering. X-ray microcomputed tomography (microCT) is a well-suited non-destructive 3D imaging technique for bone morphology. For microCT-based detection of vessels, it is paramount to use contrast enhancement. Limited differences in radiopacity between perfusion agents and mineralized bone make their distinct segmentation problematic and have been a major drawback of this approach. A decalcification step resolves this issue but inhibits the simultaneous assessment of bone microstructure and vascular morphology. The problem of contrasting becomes further complicated in samples with metal implants. This study describes contrast-enhanced microCT-based visualization of vasculature within bone tissue in small and large animal models, also in the vicinity of the metal implants. We present simultaneous microvascular and bone imaging in murine tibia, a murine bone metastatic model, the pulp chamber, gingiva, and periodontal ligaments. In a large animal model (minipig), we perform visualization and segmentation of different tissue types and vessels in the hemimandible containing metal implants. We further demonstrate the potential of dual-energy imaging in distinguishing bone tissue from the applied contrast agents. This work introduces a non-destructive approach for 3D imaging of vasculature within soft and hard tissues near metal implants in a large animal model.

physiology↗