The Novel Ultrasound Irradiation Device

Features

Dr. Katsunori Nonogaki has developed the novel ultrasound irradiation device, which can improve the autonomic nervous system activity and peripheral circulation. In addition, the ultrasoud device can improve hypertension and hyperglycemia within 20 min in subjects with drug-resistant hypertension and diabetes. Our initial device was approved in Japan (226AIBZX00028000). This device will be avaliable for the treatment of 1) muscle pain, 2) the autonomic neural dysfunction and stress-related disorders, 3) hypertention, and 4) diabetes. Moreover, the device will be usefull for your healthy life and aging care.

Targeted Application(s)/Industry

Our aims are to export the device internationally. We seek the investment and international business partners.

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 McH-lpr/lpr-RA1 mouse, a study model that spontaneously develops severe autoimmune arthritis, vasculitis, and sialadenitis

Features

McH/lpr-RA1 mice are recombinant congenic mice descended from MRL/lpr and C3H/lpr mice and develop arthritis, vasculitis, and sialadenitis with high frequency and severity, with severe pannus formation similar to rheumatoid arthritis, polyarteritis nodosa, and Sjogren's syndrome. On the other hand, McH/lpr-RA1 mice do not develop systemic lymphadenopathy and severe nephritis as seen in MRL/lpr mice, so they are easy to breed and maintain and can be used for long-term drug administration experiments.

Targeted Application(s)/Industry

Development of diagnostic and therapeutic agents for collagen diseases. It can be applied to the elucidation of the mechanism of onset of immunological adverse events caused by immune checkpoint inhibitors and the development of drugs to prevent the onset of such events, etc. Industry-academia collaboration with pharmaceutical companies, test reagent companies, etc. is possible.

Induction of Neural Cells from Human Mesenchymal Stem Cells and their Application to Neurodegenerations

Features

Bone marrow stromal cells have great advantages since they are already applied to patients either by auto- or allo-transplantations, can be harvested in large numbers (10 million cells within several weeks) as adherent cells from bone marrow aspirates, and are with low risk of tumorigenesis. We have established a system to induce neural precursor cells from human bone marrow stromal cells by introducing cells with Notch intracellular domain gene plasmid followed by culturing in neurosphere method. This induction system successfully generates neural precursors which were effective for stroke (J. Neuropathol. Exp. Neurol. , 2005; J Cereb Blood Flow Metab, 2009). They could be further developed into dopamine producing neurons by treating them with cytokines including GDNF (J. Clin. Invest, 2004). The efficiency and safety of induced dopamine neurons were confirmed by rat and monkey model of Parkinson's disease. Importantly, long-term survival of auto-transplanted induced dopamine neurons were verified by 11C-CFT PET scan (J. Clin. Invest, 2013).

Targeted Application(s)/Industry

We hope to collaborate with companies and research groups who are willing to utilize our system.

Development of Immunobiotic Evaluation System for Functional Feeds as a Livestock Animal Model

Features

Pattern recognition receptor (PRR) family plays an important role in the defense through recognition of pathogen-associated molecular patterns or microorganisms-associated molecular patterns (PAMPs/MAMPs).
Some functional feed materials are thought to regulate intestinal immunity by contact and stimulation of epithelial cells and immunocompetent cells via PRRs in the gastrointestinal tract and induction of cytokine production. In this "new world" of feed immunology, however, much remains unknown about the underlying mechanisms of intestinal immunity because of lack of appropriate intestinal immunoassay system for livestock animals.
We have advanced application of originally established porcine and bovine intestinal epitheliocytes (PIE, BIE) cell lines (see photo) for evaluation of immunobiotics and immunogenics exerting anti-inflammatory responses both in PIE cell monolayer and co-culture system with porcine peyer's patch immune cells as a peyer's patch culture model (see illustration).

Targeted Application(s)/Industry

This evaluation system may also contribute to elucidate immunoregulatory mechanism of immunobiotics and immunogenics mediated by pattern recognition receptors essential to future development of not only immunobiotic feeds but also vaccines using immunobiotics to prevent specific diseases. This can benefit mankind by offering immunobiotic feeds as a safer alternative to conventional antibiotic drug therapy.

New High-Throughput, High Resolution DNA Methylation Analysis Method, PCR-Luminex for the Diagnosis of Genomic Imprinting Disorders in ART Babies

Features

The parent-of–origin specific expression of the imprinted genes relies on DNA methylation acquired during gametogenesis. Recent studies indicate the possibility of excess imprinting disease occurrence in babies conceived by assisted reproductive technologies (ART). PCR-Luminex method is powerful tool for the methylation analyses, suitable for the use at the clinical diagnosis level because of taking much time and multistep procedures.

Targeted Application(s)/Industry

We have developed a new high-throughput, high resolution DNA methylation analysis method. PCT international patent was performed.

Peptide and Protein Designs for Unexplored Fileds

Features

I am proposing methodologies to design recombinant peptides and proteins with appropriate structures and functions in the medicinal, environmental, material, and nanotechnological fields, with molecular evolutional and domain shuffling engineering. At present, we have constructed the methodologies for efficient renaturation of functional proteins from inclusion bodies expressed in bacteria, generation of peptides and proteins with the function of biomineralization, generation of peptides and proteins with affinity for inorganic materials to spontaneously make linkages between various nanomaterials, and high enhancement of cellulolytic enzyme activity induced by nanoclustering design on nanomaterials.

Targeted Application(s)/Industry

We hope the business partners in the in the medicinal, environmental, material, and nanotechnological fields would be interested in my approaches and we could conduct effective collaboration research with them.

Oral Biofilm Functional Analysis: from “What Are They?" to “What Are They Doing?"

Features

A large number of microorganisms inhabit the oral cavity, such as the teeth, gingiva and tongue, in the form of oral biofilm. The oral cavity forms an ecosystem where the host (humans) and parasites (microorganisms) coexist. Disruption of the balance of this oral ecosystem leads to dental caries, periodontal diseases and oral malodor, and even deterioration of dental materials.

Using leading-edge techniques of anaerobic experimental systems including original and unique devices, as well as the notion of "omics" such as metagenomics and metabolomics, we conduct research on oral biofilm functions. Knowledge of oral biofilms, from "what are they?" to "what are they doing?", enables us to address their control, that is, prevention of and therapy for oral biofilm-associated diseases.

Targeted Application(s)/Industry

Risk assessment of oral biofilm-associated diseases, such as dental caries, periodontal disease, oral malodor and aspiration pneumonia
Effects of medicine and food ingredients on oral biofilm function
Evaluation of biofilm-mediated material deterioration

Extracorporeal Shock Wave Therapy as a New, Non-Invasive Angiogenic Therapy

Features

Extracorporeal shock wave (SW) therapy was introduced clinically more than 20 years ago to fragment kidney stones, which has markedly improved the treatment of urolithiasis. We found that a low-energy SW (about 10% of the energy density that is used for urolithiasis) effectively increases the expression of vascular endothelial growth factor (VEGF) in cultured endothelial cells. Based on this in vitro study, we have initiated in vivo studies and have demonstrated that extracorporeal cardiac SW therapy with a low-energy SW up-regulates the expression of VEGF, induces neovascularization, and improves myocardial ischemia in a porcine model of chronic myocardial ischemia, without any adverse effects in vivo. On the basis of promising results in animal studies, we performed a series of clinical studies in patients with severe coronary artery disease without indication of PCI or CABG, including, firstly, an open trial followed by a placebo-controlled, double-blind study. In both studies, our extracorporeal cardiac SW therapy improved symptoms, exercise capacity, and myocardial perfusion in patients with severe coronary artery disease. Importantly, no procedural complications or adverse effects were noted. The SW therapy was also effective in ameliorating left ventricular remodeling after acute myocardial infarction (MI) in pigs and in enhancing angiogenesis in hind-limb ischemia in rabbits. Based on these animal studies, we are also conducting clinical studies in patients with acute MI and in those with peripheral arterial disease. Thus, our extracorporeal cardiac SW therapy is an effective, safe, and non-invasive angiogenic approach in cardiovascular medicine and its indication could be extended to a variety of ischemic diseases in the near future.

Targeted Application(s)/Industry

The treatment for severe angina pectoris was approved as a highly advanced medical treatment by Ministry of Health, Labour and Welfare, Japan in 2010.
The low-energy SW therapy would be applicable to a wide range of diseases. Your inquiries about the collaborative research are always welcome.

The Novel Ultrasound Irradiation Device

Features

Dr. Katsunori Nonogaki has developed the novel ultrasound irradiation device, which can improve the autonomic nervous system activity and peripheral circulation. In addition, the ultrasoud device can improve hypertension and hyperglycemia within 20 min in subjects with drug-resistant hypertension and diabetes. Our initial device was approved in Japan (226AIBZX00028000). This device will be avaliable for the treatment of 1) muscle pain, 2) the autonomic neural dysfunction and stress-related disorders, 3) hypertention, and 4) diabetes. Moreover, the device will be usefull for your healthy life and aging care.

Targeted Application(s)/Industry

Our aims are to export the device internationally. We seek the investment and international business partners.

Induction of Schwann cells from human mesenchymal stem cells and their application to spinal cord injury and demyelinating diseases

Features

Bone marrow stromal cells have great advantages since they are already applied to patients either by auto- or allo-transplantations, can be harvested in large numbers (10 million cells within several weeks) as adherent cells from bone marrow aspirates, and are with low risk of tumorigenesis. Furthermore, marrow bank is available. Likewise, mesenchymal cells harvested from umbilical cord are also easily accessible from cord bank and are a good source of mesenchymal stem cells. We have established a system to induce functional Schwann cells (peripheral glia) from human bone marrow stromal cells and umbilical cord mesenchymal cells by treating cells with a series of reagents and cytokines. This induction system successfully generates Schwann cells with very high efficiency (~97%). They were confirmed to elicit neural regeneration in peripheral nerve damages and spinal cord injury (Eur, J. Neurosci, 2001; J. Neurosurg, 2004, J. Neuropathol. Exp. Neurol, 2005, Biochem Biophys Res Commun, 2007; Tissue Eng., 2011). The efficiency and safety of induced Schwann cells were demonstrated in monkey by 1 year follow up (Exp. Neurol., 2010). Importantly, induced cells not only elicited neural regeneration in both peripheral and central nervous system, but also contributed to functional recovery by restoring myelin and saltatory conduction. Therefore, these cells are expected to be effective to demyelinating diseases as well. We hope to collaborate with companies and research groups who are willing to utilize our system.

Targeted Application(s)/Industry