Structure and Function of Connective Tissue in Cardiac Muscle: Collagen Types I and III in Endomysial Struts and Pericellular Fibers

Heart myocytes and capillaries are enmeshed in a complex array of connective tissue structures arranged in several levels of organization: epimysium, the sheath of connective tissue that surrounds muscles; perimysium, which is associated with groups of cells; and endomysium, which surrounds and interconnects individual cells. The present paper is a review of work in this field with an emphasis on new, unpublished findings, including composition of endomysial fibers and disposition of newly described perimysial fibers. The role of scanning electron microscopy in the development of current understanding is also outlined. Biaxially arranged epimysial fibers form a sheath around papillary muscles and trabeculae that becomes increasingly well-oriented with the muscle axis during stretch. Perimysial structures are associated with groups of cells, and include weaves and septa of collagen, tendon-like fibers between weaves, ribbon-like fibers perpendicular to myocytes, and the newly described coiled perimysial fibers, which form an array in parallel with the myocytes and the epimysial net. The endomysium includes struts that bridge cells and pericellular fibers; both contain collagen types I and III. The evidence for the latter is presented in this paper and depends upon the use of antibody localization with fluorescent markers in light microscopy and colloidal gold for scanning electron microscopy. The implications of the composition of collagen fibers for myocardial function are discussed in relation to intra-cellular and other extra-cellular structures

HIV-1 evades virus-specific IgG2 and IgA responses by targeting systemic and intestinal B cells via long-range intercellular conduits

Contact-dependent communication between immune cells generates protection but also facilitates viral spread. Here we found that macrophages formed long-range actin-propelled conduits in response to negative factor (Nef), a human immunodeficiency virus type 1 (HIV-1) protein with immunosuppressive functions. Conduits attenuated immunoglobulin G2 (IgG2) and IgA class switching in systemic and intestinal lymphoid follicles by shuttling Nef from infected macrophages to B cells through a guanine-exchange factor-dependent pathway involving the amino-terminal anchor, central core and carboxy-terminal flexible loop of Nef. By showing stronger virus-specific IgG2 and IgA responses in patients with Nef-deficient virions, our data suggest that HIV-1 exploits intercellular 'highways' as a 'Trojan horse' to deliver Nef to B cells and evade humoral immunity systemically and at mucosal sites of entr

Modeling Patient-Derived Glioblastoma with Cerebral Organoids

Summary: The prognosis of patients with glioblastoma (GBM) remains dismal, with a median survival of approximately 15 months. Current preclinical GBM models are limited by the lack of a “normal” human microenvironment and the inability of many tumor cell lines to accurately reproduce GBM biology. To address these limitations, we have established a model system whereby we can retro-engineer patient-specific GBMs using patient-derived glioma stem cells (GSCs) and human embryonic stem cell (hESC)-derived cerebral organoids. Our cerebral organoid glioma (GLICO) model shows that GSCs home toward the human cerebral organoid and deeply invade and proliferate within the host tissue, forming tumors that closely phenocopy patient GBMs. Furthermore, cerebral organoid tumors form rapidly and are supported by an interconnected network of tumor microtubes that aids in the invasion of normal host tissue. Our GLICO model provides a system for modeling primary human GBM ex vivo and for high-throughput drug screening. : To address limitations with current preclinical glioblastoma (GBM) models, Linkous et al. establish a “GLICO” (cerebral organoid glioma) model to retro-engineer patient-specific GBMs using patient-derived glioma stem cells and human cerebral organoids. Resulting tumors closely phenocopy patient GBMs and are supported by tumor microtubes that promote invasion into host tissue. Keywords: cerebral organoids, glioma stem cells, glioblastoma, glioma, tumor microtubes, human embryonic stem cells, brain tumors, stem-cell-based disease models, tissue engineering, cancer stem cell