Hiroshi Shimoda

Bio: Hiroshi Shimoda is an academic researcher from Hirosaki University. The author has contributed to research in topics: Lymphatic system & Lymphatic Endothelium. The author has an hindex of 16, co-authored 65 publications receiving 789 citations. Previous affiliations of Hiroshi Shimoda include Oita University & Osaka University.

Engineered whole cut meat-like tissue by the assembly of cell fibers using tendon-gel integrated bioprinting

Abstract: With the current interest in cultured meat, mammalian cell-based meat has mostly been unstructured. There is thus still a high demand for artificial steak-like meat. We demonstrate in vitro construction of engineered steak-like tissue assembled of three types of bovine cell fibers (muscle, fat, and vessel). Because actual meat is an aligned assembly of the fibers connected to the tendon for the actions of contraction and relaxation, tendon-gel integrated bioprinting was developed to construct tendon-like gels. In this study, a total of 72 fibers comprising 42 muscles, 28 adipose tissues, and 2 blood capillaries were constructed by tendon-gel integrated bioprinting and manually assembled to fabricate steak-like meat with a diameter of 5 mm and a length of 10 mm inspired by a meat cut. The developed tendon-gel integrated bioprinting here could be a promising technology for the fabrication of the desired types of steak-like cultured meats. Mammalian cell-based cultured meat has mostly been unstructured, leaving a demand for artificial steak-like meat. Here the authors present an assembled steak-like tissue of bovine skeletal muscle, adipose tissue, and blood capillary tissue fabricated by tendon-gel integrated printing technology.

Lymphangiogenesis and expression of specific molecules as lymphatic endothelial cell markers

Abstract: In recent years, several functional molecules specifically expressed and localized in lymphatic endothelial cells, such as 5’-nucleotidase, lymphatic vessel endothelial receptor-1, vascular endothelial growth factor receptor-3, podoplanin and Prox-1, have been identified The discovery of the lymphatic endothelial cell markers facilitated detailed analysis of the nature and structural organization of the lymphatic vessels and their growth (lymphangiogenesis) As a result, over the past few years, advances have been made in understanding the cellular and molecular aspects of physiological lymphangiogenesis and tumor-induced lymphangiogenesis The biology of lymphangiogenesis, particularly the mechanism of its regulation, is very important in understanding the formation of the lymphatic system as a biological regulation system transporting tissue fluid and wandering cells, including lymphocytes, and disease involving lymphangiogenesis The understanding of the molecular mechanism of lymphangiogenesis and the elucidation of the development of normal and pathological tissues are expected to lead to the development of therapy for intractable diseases, such as malignant tumors and lymphedema

Abnormal recruitment of periendothelial cells to lymphatic capillaries in digestive organs of angiopoietin-2-deficient mice

Abstract: The fine structure of lymphatic capillaries in the digestive organs of angiopoietin-2 (Ang2) knockout mice was studied by using both immunohistochemistry and electron microscopy. The genetic deletion of Ang2 yielded hypoplasia and disorganization of the lymphatic capillaries, with their shapes being irregular, and an aberrant recruitment of vascular periendothelial cells immunopositive for smooth muscle actin to the lymphatic capillaries. The abnormal lymphatic periendothelial cells were considered to be a type of pericyte for the lymphatic capillaries after the deletion of Ang2, because they were ultrastructurally characterized by abundant thin myofilaments in their cytoplasm and long cytoplasmic extensions similar to those shown by blood vascular pericytes. The genetic replacement of Ang2 with Ang1 rescued the defects, viz., the disorganization and disordered structure of the lymphatic capillaries. The present findings suggest that Ang2 serves the morphogenesis of lymphatic capillaries as an agonist for the receptor, Tie2, and that Ang1 can replace Ang2 in guiding lymphatic formation and development.

A dural lymphatic vascular system that drains brain interstitial fluid and macromolecules

Abstract: The central nervous system (CNS) is considered an organ devoid of lymphatic vasculature. Yet, part of the cerebrospinal fluid (CSF) drains into the cervical lymph nodes (LNs). The mechanism of CSF entry into the LNs has been unclear. Here we report the surprising finding of a lymphatic vessel network in the dura mater of the mouse brain. We show that dural lymphatic vessels absorb CSF from the adjacent subarachnoid space and brain interstitial fluid (ISF) via the glymphatic system. Dural lymphatic vessels transport fluid into deep cervical LNs (dcLNs) via foramina at the base of the skull. In a transgenic mouse model expressing a VEGF-C/D trap and displaying complete aplasia of the dural lymphatic vessels, macromolecule clearance from the brain was attenuated and transport from the subarachnoid space into dcLNs was abrogated. Surprisingly, brain ISF pressure and water content were unaffected. Overall, these findings indicate that the mechanism of CSF flow into the dcLNs is directly via an adjacent dural lymphatic network, which may be important for the clearance of macromolecules from the brain. Importantly, these results call for a reexamination of the role of the lymphatic system in CNS physiology and disease.

Gastrointestinal stromal tumors.

Abstract: Background We reviewed radiologic features of gastrointestinal stromal tumors (GISTs) and correlated them with clinical and pathologic findings.

Extracellular Matrix in the Tumor Microenvironment and Its Impact on Cancer Therapy

Abstract: Solid tumors are complex organ-like structures that consist not only of tumor cells but also of vasculature, extracellular matrix (ECM), stromal, and immune cells. Often, this tumor microenvironment (TME) comprises the larger part of the overall tumor mass. Like the other components of the TME, the ECM in solid tumors differs significantly from that in normal organs. Intratumoral signaling, transport mechanisms, metabolisms, oxygenation, and immunogenicity are strongly affected if not controlled by the ECM. Exerting this regulatory control, the ECM does not only influence malignancy and growth of the tumor but also its response toward therapy. Understanding the particularities of the ECM in solid tumor is necessary to develop approaches to interfere with its negative effect. In this review, we will also highlight the current understanding of the physical, cellular, and molecular mechanisms by which the pathological tumor ECM affects the efficiency of radio-, chemo-, and immunotherapy. Finally, we will discuss the various strategies to target and modify the tumor ECM and how they could be utilized to improve response to therapy.

Outflow of cerebrospinal fluid is predominantly through lymphatic vessels and is reduced in aged mice.

Abstract: Cerebrospinal fluid (CSF) has been commonly accepted to drain through arachnoid projections from the subarachnoid space to the dural venous sinuses. However, a lymphatic component to CSF outflow has long been known. Here, we utilize lymphatic-reporter mice and high-resolution stereomicroscopy to characterize the anatomical routes and dynamics of outflow of CSF. After infusion into a lateral ventricle, tracers spread into the paravascular spaces of the pia mater and cortex of the brain. Tracers also rapidly reach lymph nodes using perineural routes through foramina in the skull. Using noninvasive imaging techniques that can quantify the transport of tracers to the blood and lymph nodes, we find that lymphatic vessels are the major outflow pathway for both large and small molecular tracers in mice. A significant decline in CSF lymphatic outflow is found in aged compared to young mice, suggesting that the lymphatic system may represent a target for age-associated neurological conditions.