Developmentally-Inspired Biomimetic Culture Models to Produce Functional Islet-Like Cells From Pluripotent Precursors

Scientists highlight the development of in vitro cell culture models that allow systematic studies of pancreatic cell mechanobiology in response to extracellular matrix proteins, biomechanical effects, soluble factor modulation of biomechanics, substrate stiffness, fluid flow and topography.
[Frontiers in Bioengineering and Biotechnology]
Tran, R., Moraes, C., & Hoesli, C. A. (2020). Developmentally-Inspired Biomimetic Culture Models to Produce Functional Islet-Like Cells From Pluripotent Precursors. Frontiers in Bioengineering and Biotechnology, 8. https://doi.org/10.3389/fbioe.2020.583970 Cite
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Microglia-Organized Scar-Free Spinal Cord Repair in Neonatal Mice

Scientists transplanted either neonatal microglia or adult microglia treated with peptidase inhibitors into spinal cord lesions of adult mice, and found that both types of microglia significantly improved healing and axon regrowth.
[Nature]
Li, Y., He, X., Kawaguchi, R., Zhang, Y., Wang, Q., Monavarfeshani, A., Yang, Z., Chen, B., Shi, Z., Meng, H., Zhou, S., Zhu, J., Jacobi, A., Swarup, V., Popovich, P. G., Geschwind, D. H., & He, Z. (2020). Microglia-organized scar-free spinal cord repair in neonatal mice. Nature, 1–6. https://doi.org/10.1038/s41586-020-2795-6 Cite
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SHP2 Is a Multifunctional Therapeutic Target in Drug Resistant Metastatic Breast Cancer

Scientists used inducible genetic depletion and two distinct pharmacological inhibitors to investigate the therapeutic potential of targeting SH2 containing protein tyrosine phosphatase-2 (SHP2) in metastatic breast cancer.
[Oncogene]
Chen, H., Libring, S., Ruddraraju, K. V., Miao, J., Solorio, L., Zhang, Z.-Y., & Wendt, M. K. (2020). SHP2 is a multifunctional therapeutic target in drug resistant metastatic breast cancer. Oncogene, 1–15. https://doi.org/10.1038/s41388-020-01488-5 Cite
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Immune Remodeling of the Extracellular Matrix Drives Loss of Cancer Stem Cells and Tumor Rejection

Extracellular matrix-rich tumors exhibited a stem cell-like gene expression profile and superior tumor-initiating capacity, whereas such features were absent in responder tumors.
[Cancer Immunology Research]
Pires, A., Greenshields-Watson, A., Jones, E., Smart, K., Lauder, S. N., Somerville, M., Milutinovic, S., Kendrick, H., Hindley, J. P., French, R., Smalley, M. J., Watkins, W. J., Andrews, R., Godkin, A., & Gallimore, A. (2020). Immune Remodelling of the Extracellular Matrix Drives Loss of Cancer Stem Cells and Tumor Rejection. Cancer Immunology Research. https://doi.org/10.1158/2326-6066.CIR-20-0070 Cite
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Inhibition of eNOS by L-NAME Resulting in Rat Hind Limb Developmental Defects through PFKFB3 Mediated Angiogenetic Pathway

In vivo studies showed that NOS inhibition strongly suppressed hind limb angiogenetic remodeling by impairing differentiation of endothelial cells and smooth muscle cells, and extracellular matrix synthesis.
[Scientific Reports]
Wu, Z., Yao, H., Xu, H., Wang, Y., Hu, W., Lou, G., Zhang, L., Huang, C., Jiang, C., Zhou, S., Shi, Y., Chen, X., Yang, L., Xu, Y., & Wang, Y. (2020). Inhibition of eNOS by L-NAME resulting in rat hind limb developmental defects through PFKFB3 mediated angiogenetic pathway. Scientific Reports, 10(1), 16754. https://doi.org/10.1038/s41598-020-74011-1 Cite
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Immune Remodelling of the Extracellular Matrix Drives Loss of Cancer Stem Cells and Tumor Rejection

Scientists defined an extended role for an effective immune response, not just in direct killing of tumor cells, but in widescale remodelling of the tumor microenvironment to favor loss of ECM, elimination of cancer stem cells, and propagation of adaptive immunity.
[Cancer Immunology Research]
Pires, A., Greenshields-Watson, A., Jones, E., Smart, K., Lauder, S. N., Somerville, M., Milutinovic, S., Kendrick, H., Hindley, J. P., French, R., Smalley, M. J., Watkins, W. J., Andrews, R., Godkin, A., & Gallimore, A. (2020). Immune Remodelling of the Extracellular Matrix Drives Loss of Cancer Stem Cells and Tumor Rejection. Cancer Immunology Research. https://doi.org/10.1158/2326-6066.CIR-20-0070 Cite
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Controllable Gelation of Artificial Extracellular Matrix for Altering Mass Transport and Improving Cancer Therapies

The authors report a fibrinogen and thrombin based coagulation system to construct an artificial ECM for selectively cutting-off the tumor metabolic flux.
[Nature Communications]
Zheng, D.-W., Hong, S., Zhang, Q.-L., Dong, X., Pan, P., Song, W.-F., Song, W., Cheng, S.-X., & Zhang, X.-Z. (2020). Controllable gelation of artificial extracellular matrix for altering mass transport and improving cancer therapies. Nature Communications, 11(1), 4907. https://doi.org/10.1038/s41467-020-18493-7 Cite
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Fibroblast Growth Factor Receptor 3 Activates a Network of Profibrotic Signaling Pathways to Promote Fibrosis in Systemic Sclerosis

Investigators demonstrated that the profibrotic cytokine transforming growth factor β selectively up-regulated fibroblast growth factor receptor 3 (FGFR3) and its ligand FGF9 to promote fibroblast activation and tissue fibrosis, leading to a prominent FGFR3 signature in the systemic sclerosis skin.
Chakraborty, D., Zhu, H., Jüngel, A., Summa, L., Li, Y.-N., Matei, A.-E., Zhou, X., Huang, J., Trinh-Minh, T., Chen, C.-W., Lafyatis, R., Dees, C., Bergmann, C., Soare, A., Luo, H., Ramming, A., Schett, G., Distler, O., & Distler, J. H. W. (2020). Fibroblast growth factor receptor 3 activates a network of profibrotic signaling pathways to promote fibrosis in systemic sclerosis. Science Translational Medicine, 12(563). https://doi.org/10.1126/scitranslmed.aaz5506 Cite
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Hyaluronan Regulates Synapse Formation and Function in Developing Neural Networks

Scientists used 3D cortical spheroids derived from human iPSCs to replicate the neurodevelopmental window. Their results demonstrated that hyaluronan preferentially surrounds nascent excitatory synapses.
[Scientific Reports]
Wilson, E., Knudson, W., & Newell-Litwa, K. (2020). Hyaluronan regulates synapse formation and function in developing neural networks. Scientific Reports, 10(1), 16459. https://doi.org/10.1038/s41598-020-73177-y Cite
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H3.3G34W Promotes Growth and Impedes Differentiation of Osteoblast-Like Mesenchymal Progenitors in Giant Cell Tumour of Bone

Investigators showed that H3.3K36me3 loss on mutant H3.3 altered the deposition of the repressive H3K27me3 mark from intergenic to genic regions, beyond areas of H3.3 deposition. This promoted redistribution of other chromatin marks and aberrant transcription, altering cell fate in mesenchymal progenitors and hindering differentiation.
[Cancer Discovery]
Khazaei, S., Jay, N. D., Deshmukh, S., Hendrikse, L. D., Jawhar, W., Chen, C. C., Mikael, L. G., Faury, D., Marchione, D. M., Lanoix, J., Bonneil, E., Ishii, T., Jain, S. U., Rossokhata, K., Sihota, T. S., Eveleigh, R., Lisi, V., Harutyunyan, A. S., Jung, S., … Jabado, N. (2020). H3.3G34W promotes growth and impedes differentiation of osteoblast-like mesenchymal progenitors in Giant Cell Tumour of Bone. Cancer Discovery. https://doi.org/10.1158/2159-8290.CD-20-0461 Cite
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Peptide-Protein Coassembling Matrices as a Biomimetic 3D Model of Ovarian Cancer

Researchers used peptide amphiphiles (PAs) to coassemble with and organize extracellular matrix (ECM) proteins producing tunable 3D models of the tumor microenvironment. They included specific epitopes, PA nanofibers, and ECM macromolecules for the 3D culture of human ovarian cancer, endothelial, and mesenchymal stem cells.
[Science Advances]
Hedegaard, C. L., Redondo-Gómez, C., Tan, B. Y., Ng, K. W., Loessner, D., & Mata, A. (2020). Peptide-protein coassembling matrices as a biomimetic 3D model of ovarian cancer. Science Advances, 6(40), eabb3298. https://doi.org/10.1126/sciadv.abb3298 Cite
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