Basic Medicine, Molecular and Cellular Biology
Transplantation and Regenerative Medicine
The Establishment of Next-Generation Cell Therapy Based on Islet Transplantation
Medical Sciences Course
- Master / Doctoral Degree
- GOTO, Masafumi
Professor, M.D. Ph.D.
masafumi.goto.c6*tohoku.ac.jp (Please convert "*" into "@".)
- Development of newly recombinant digesting enzymes for islets and various types of cell isolation
- Development of an immunoisolating device for Bioartificial pancreatic islets
- Establishment of novel effective protocols for performing hepatocyte transplantation
islet transplantation, hepatocyte transplantation, cell islolation enzymes, bioartificial pancreatic islets, next-generation cell therapy
cell culture, tissue and cell isolation, cell transplantation, in vivo / in vitro imaging, histopathology
Islet transplantation is a less invasive type of tissue transplantation which is used to treat diabetic patients. In contrast to pancreas transplantation, islet transplantation only requires the use of local anaesthesia and percutaneous cannulation to transplant isolated islets. The major obstacle associated with islet transplantation is a the need to obtain multiple donors in order to cure one diabetic patient. This is mainly due to the unstable and insufficient islet yield which is related to such factors as the poor quality of islet isolating enzymes, a low islet functionality, and poor engraftment. The need to administer immunosuppressants to prevent graft rejection also results in the occurrence of several adverse effects experienced by the recipients.
Our main research interests focus on addressing these problems. We have developed genetically engineered cell isolating enzymes produced by recombinant DNA technology. These novel enzymes can eliminate batch to batch differences, consequently making it possible to optimize the enzyme components according to the structure of specific tissues. Improvements in the islet yield and function have already been reported in pre-clinical study and clinical trials that are currently going on. Such improvements are expected to also be applicable for other types of cell therapy, such as hepatocyte transplantation. Several studies from our laboratory, including the development of a novel evaluation method for the islet function and a novel regimen for facilitating engraftment by resting transplanted islet grafts, are already being used in clinical practice. We are also attempting to develop a bioartificial pancreatic islet device to enable patients to avoid the use of immunosuppressants.
Our ultimate goal is to make islet transplantation the standard therapy for diabetes, and also establish new types of next-generation cell therapy for various diseases.
Figure 1. Development of safe and efficient enzymes for cell isolation
Figure 2. High-sensitive imaging system for islet grafts
- Maeda, et, al. Cloning a neutral protease of Clostridium histolyticum, determining its substrate specificity, and designing a specific substrate. Applied Microbiology and Biotechnology 2015 Aug 26 (Epub ahead oh print)
- Dendo M, et al. Synergistic effect of neutral protease and clostripain on pancreatic islet isolation. Transplantation. in press, 2015
- Jimbo T, et al. A novel resting strategy for improving islet engraftment in the liver. Transplantation. 97(3):280-286, 2014
- Fujio A, et al. Collagenase H is crucial for isolation of rat pancreatic islets. Cell Transplantation. 23(10):1187-1198, 2014
- Nishimura R, et al. Tacrolimus inhibits the revascularization of isolated pancreatic islets. PLOS ONE. 8(4):e56799, 2013