• Effective drug delivery to central nervous system is promising as a new therapeutic strategy against various central nervous system disorders. However, it represents a challenge because systemic delivery is always hindered by blood brain barrier, and local delivery cannot be effective because of the restricted distribution. Recently, local drug delivery system that can achieve robust distribution of the infusates by maintaining a pressure gradient at the tip of the infusion catheter during infusion has developed. Although this method is promising, there still exist several problems as loss of infusates by backflow through catheter tract or inconsistent distribution. We recently developed a method to deliver agents with this method under MRI guidance, and now performing clinical trial to treat recurrent gliomas.

Focal central nervous system disorders such as tumor, epilepsy, and parkinson's disease can be the target for application of this technique. Developments of the new catheters and pre-infusional similation systems are on their way. We are searching for effective collaborative research in this field.

• 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).

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

• 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.

• 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 skeletal muscle cells from human bone marrow stromal cells by treating cells with cytokines followed by Notch intracellular domain gene plasmid introduction. This induction system successfully generates skeletal muscle lineage cells comprised of muscle stem cells, namely, satellite cells, as well as myoblasts and myotubes. Transplantation of satellite cells and myoblasts were effective for muscle regeneration (Science, 2005). Importantly, induced satellite cells integrated into satellite cell location and continuously contributed to muscle regeneration. Our research team is now pursuing the safety and efficiency of these induced cells by using canine muscle degeneration models. We hope to collaborate with companies and research groups who are willing to utilize our system.

• Strong points
• Anemia is a very prevalent disease. Nevertheless, an effective therapy is yet to be discovered. Erythropoietin is effective only for those with renal dysfunction. We have found that inhibition of an enzyme for epigenetic regulation results in a prominent increase of erythropoiesis, pointing to a new target for anemia therapy. We have also generated a new, cell-based assay system for the enzymatic activity and carried out small molecule screening.
• Collaboration with industry partners
• We are seeking a collaboration to accelerate the development of new anemia drugs based on these findings. Together we will advance the development of the candidate molecules currently identified as well as conduct further screening of larger chemical space for better candidates and/or for drug repositioning.

• AIMS: The invention is to analyze metabolic condition, especially in oxygen consumption and energy production in the adipose tissues of human (Patent: JP 3848818).
• PROBLEM TO BE SOLVED: To provide an instrument and method for analyzing the metabolism condition of a living body which is constructed in such a manner that it can measure the metabolism condition of a living body correctly and easily, and a recording medium.
• SOLUTION: A metabolism condition analyzer is provided with an input means for inputting information about the body of a subject, a control means for processing this information and an output means for outputting results of the processing. The information consists of name, age, sex, race, height, weight, bioelectric resistance value and the date and time of measurement. A data file consisting the control means stores evaluation data of a metabolic condition which is previously determined by medical judgment based on a combination of an internal respiration index and oxygen consumption and energy production in adipose tissues. These are computed by calculating the value obtained by subtracting one from a body density calculated from the height, weight of the subject and the bioelectric resistance value and then multiplying the value. Welcome to your investment or co-operation.

• Primary aldosteronism is a leading cause of secondary hypertension accounting for approximately 10 % of hypertensive patients; 4 million patients potentially exist in Japan. We aim to optimize the method of ablating aldosterone producing adenoma using newly developed bipolar radiofrequency ablation system with 300-400kHz high-frequency current and electric power of 40W (Celon Prosurge Applicator), and establish a less invasive interventional radiological treatment of primary aldosteronism.

Collaboration with medical equipment manufacture and universities are expected to develop new devices enabling ablation of aldosterone producing adenoma. Flexible guide-wire-type ablation system and rapid aldosterone assay system should be co-developed to tread aldosterone producing microadenoma which is difficult to detect due to its small diameter of less than 5mm.