Department of Organ Reconstruction, Institute for Frontier Medical Sciences, Kyoto University Japanese
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Research
■Research History

 Former Professor Kazutomo Inoue moved from Department of Surgery, Kyoto University Hospital with his research group to this Department in 1998, shortly after the foundation of the Institute. He and his research group intensely studied innovative therapy for diabetes mellitus, such as islet transplantation, bio-artificial pancreas, pancreas regeneration and so on from the late 1980s. He directed head office as a chairperson of the Japanese Pancreas and Islet Transplantation Association (JPITA) and he held the First Meeting of Japanese Society for Regenerative Medicine (JSRM) in 2002. Shoichiro Sumi, as an associate professor, took over Professor Inoue’s job after his retirement in 2003.

 

■Research Outline

  The mission of our department is to study regenerative medicine for endocrine and metabolic diseases to develop novel therapeutic approaches. Among such diseases, our major target is Diabetes Mellitus (DM).
DM is a leading cause of morbidity and mortality in industrialized countries, and the number of patients is estimated to be 366 million in 2011 and to become 552 million by 2030 (International Diabetes Federation, Diabetes Atlas, 5th Edition, 2011). DM causes not only symptoms due to acute hyperglycemia but also nephropathy (renal failure), retinopathy (blindness), neuropathy (insensitivity to pain, etc.), gangrene (amputation of extremities) and so on through progressive microangiopathy due to chronic hyperglycemia. Therefore, it is an urgent necessity to develop a universal therapeutic method to cure diabetes mellitus.
To this goal, we are currently working on ・・・
1. Bioartificial pancreas (BAP): BAP enables allo- or xeno-transplantation of islets or in vitro-processed islet-like cells without immunosuppression. Fig.1 shows the mechanism of BAP (islets or islet-like cells surrounded by semi-permeable membrane or gel).


1. Bioartificial pancreas (BAP): BAP enables allo- or xeno-transplantation of islets or in vitro-processed islet-like cells without immunosuppression. Fig.1 shows the mechanism of BAP (islets or islet-like cells surrounded by semi-permeable membrane or gel).


  (Fig. 1)

We have uniquely developed PVA (poly-vinyl alcohol) macro-encapsulated islets by freezing-thawing method and showed its feasibility in rats and mice. PVA hydrosolution becomes gel through PVA micro-crystallization at low temperature. We combined this and the technique of islet cryopreservation.
Now, we are trying to develop PVA-macroencapsulated porcine islets for future clinical application. Fig.2 shows PVA-macroencapsulated rat islets.


  (Fig. 2)

2. Differentiation and/or preparation of islet-like cells: As the bio-resource for diabetes therapy, we are working on ES, iPS and several kinds of somatic stem cells, such as pancreatic stem-like cells and fusion cells between islet cells and bone marrow-derived mesenchymal stem cells (MSCs). Fig.3 and 4 shows islet-like cell cluster differentiated from mouse ES cells and electrically fused cells between islet cells and MSCs, respectively.

(Fig. 3)
(Fig. 4)

3. Studies on neovascularization: We have developed an effective method to induce neovascularization at subcutaneous site for transplantation of islets or BAP. We are trying to develop specialized neovascularization method for subcutaneous transplantation of PVA-macroencapsulated islets.

4. Simulator of systemic glucose metabolism: The simulator that can predict glucose levels in a patient will be applicable to model-predicted control of mechanical artificial pancreas.

5. Others: We are planning new studies to apply PVA-macroencapsulation and/or cell fusion techniques for other types of cells including hepatocyte.

 

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