New Developments in Bone Regenerative Therapy

Features

Octacalcium phosphate/collagen composites (OCP/Col: BonarcⓇ), a bone regenerative material commercialized in 2019, outperforms the bone regeneration of existing bone substitutes and is cost-effective and easy to use. Recently, we have demonstrated that the addition of teriparatide (TPTD: a parathyroid hormone for the treatment of osteoporosis) to OCP/Col, or improvements in the manufacturing process of OCP/Col, would expand their use for intractable bone defects and bone augmentation, which is difficult to treat.

Targeted Application(s)/Industry

As a medical devise of bone regenerative material, expansion of application in various bone defect (orthopedic surgery, neurosurgery, etc.) and overseas expansion would be expected. Furthermore, as a combination product based on OCP/Col would provide a therapeutic alternative for difficult bone defects or urgent surgery.

Noninvasive Ultrasonic Measurement of Dynamic Properties of Heart and Arteries

Features

Complexity of the cardiac contraction sequence is still not fully understood because the dynamic mechanical excitation process, which directly correlates with contraction, cannot be accurately measured by CT, MRI, SPECT, or conventional ultrasound. By developing a noninvasive novel imaging modality with high temporal and spatial resolutions (US patent 5840028), we have detected the minute mechanical response (velocity component) to the propagation of the action potential in the human heart or to detect the propagation of the vibrations along the heart wall caused by the valve closure (Fig. 2).
By applying the same procedure to the human arteries, the regional change in wall thickness caused during one cardiac cycle can be measured with high spatial resolution (Fig. 1). From the measurement, the regional elasticity of tissue surrounding atherosclerotic plaque can be determined. By comparing the pathological findings with the distribution of elasticity, elasticity of lipid and that of fibrous tissue were determined. Thus, each point inside the plaque is classified into lipid or fibrous tissue using transcutaneous ultrasound (Fig. 3).

Targeted Application(s)/Industry

This novel method offers potential as a diagnostic technique for detection of plaque vulnerability with high spatial resolution.
We are prepared to provide academic consultations to companies interested in our research.

Development of Nano-Medical-Agricultural Applied Technology Using Ion-Controlled Plasma

Features

Since we have developed the techniques (ion control plasma) to generate and control ions, electrons, reactive species (radicals) in the low temperature non-equilibrium plasmas which I can touch by hand, the composite materials using nanoparticles, nanocarbons, biological molecules are synthesized in the nano-electronics field, the minimally-invasive and highly-efficient drug/gene transfection systems are developed in the medical field, and bacteria and insects are killed by the plasma in place of pesticide in the agricultural field.

Targeted Application(s)/Industry

The ion-controlled plasmas are applied for the minimally-invasive gene transfection system, next-generation agricultural system, the electrode material of highly-efficient battery, and so on. We hope to conduct the collaborative research with a willing company for a practical application of the novel plasma nano-medical-agricultural applied technology in industry.

Clinical Applications of Motion Capture System for Living Body

Features

We have developed a wireless motion capture system for living body that could non-invasively measure various biological movements without any contact. By utilizing the LC resonant magnetic marker due to the latest magnetic engineering technology, we have achieved a magnetic wireless system which could be used even in a shielded space such as oral cavity by applying a magnetic field from outside the body. By using the infrared reflective markers of small and light, we have also succeeded in developing an optical system capable of synchronous real-time measurement at up to 50 locations at 250 hertz.

Targeted Application(s)/Industry

This new system can three dimensionally analyze various biological movements and can be applied to such diagnostic and medical equipment that requires a motion analysis non-invasively without any contact. It is possible to specialize this system to suit the required conditions, so I would like to joint research with companies and organizations that want to take advantage of this system.

Exercising "Cultured" Myotubes!

Features

We succeeded in generating highly developed cultured C2C12 myotubes by manipulating intracellular Ca2+ transients with electric pulse stimulation (EPS), that are endowed with similar properties to in vivo skeletal muscle in terms of (1) excitation-induced contractile activity as a result of de novo sarcomere formation, (2) higher energy expenditure (as assessed by AMPK activation), and (3) improved insulin responsiveness (as assessed by exofacial myc-GLUT4 translocation assay).

Targeted Application(s)/Industry

Taking advantage of our “in vitro Exercise Model", our innovation will be an excellent alternative for the animal experimentation that can be applicable for a wide array of skeletal muscle research including drug screen.

Development of devices regulating inter-organ neural network for diabetes therapy

Features

Diabetes induces several complications, including retinopathy and nephropathy. In patients with type 1 diabetes as well as those with type 2 diabetes, pancreatic beta cells have reportedly decreased. Therefore, regeneration therapy of pancreatic beta cells may be very effective for major populations of diabetic patients. We discovered a neuronal network, from the liver, which selectively elicits pancreatic beta cell proliferation (Science 2008, Fig.). In a murine model with insulin-deficient diabetes, stimulation of this network improved diabetes. Thus, building devices which regulate the inter-organ neuronal network may lead to “regenerative therapy” for diabetes which regenerates pancreatic beta cells in the pancreas using patients’ own cells and patients’ own systems. We hope to conduct collaborative research with a willing company for a practical application of this technology.

Development of New Drugs and Devices Regulating Inter-Organ Neural Network for Obesity Therapy

Features

Obesity induced the metabolic syndrome, which causes cardiovascular diseases. Obesity has now become a major health concern not only in developed countries but developing countries. However, diet and exercise are still major therapies. We discovered endogenous systems maintaining homeostasis of energy metabolism and revealed several neuronal networks among organs to be responsible for the regulation systems.
1) Afferent neuronal signals from adipose tissue regulate appetite and prevent over-eating during obesity development (Cell Metab 2006)
2) Neuronal network from the liver enhances basal metabolic rates to prevent obesity development when energy store is increasing (Science 2006) 3) Neuronal network from the liver suppresses adaptive thermogenesis in brown adipose tissue (Cell Metab 2012).

Targeted Application(s)/Industry

On the basis of these original discoveries, we are aiming at developing new drugs and/or building devices which regulate the inter-organ neuronal networks and hope to conduct collaborative research with a willing company for a practical application to obesity therapy.

Production of Tumor-Specific Monoclonal Antibodies

Features

Podoplanin (PDPN/Aggrus/T1α), a platelet aggregation-inducing mucin-like sialoglycoprotein, is highly expressed in many cancers and normal tissues. A neutralizing monoclonal antibody (mAb; NZ-1) can block the association between podoplanin and C-type lectin-like receptor-2 (CLEC-2) and inhibit podoplanin-induced cancer metastasis, but NZ-1 reacts with podoplanin-expressing normal cells such as lymphatic endothelial cells. Recently, we established a platform to produce cancer-specific mAbs (CasMabs). The newly established LpMab-2 mAb reacted with podoplanin-expressing cancer cells but not with normal cells, as shown by flow cytometry and immunohistochemistry; therefore, LpMab-2 is an anti-podoplanin CasMab that is expected to be useful for molecular targeting therapy against podoplanin-expressing cancers.

Targeted Application(s)/Industry

We can produce cancer-specific mAbs (CasMabs) against all membranous proteins. CasMabs are expected to be useful for molecular targeting therapy without side effects.