| Co-Investigator(Kenkyū-buntansha) |
YAMASHINA Shohei Kitasato University, School of Medicine, Professor, 医学部, 教授 (90013987)
TAKAHASHI Tuyoshi Kitasato University, School of Medicine, Associate professor, 医学部, 助教授 (70245405)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2005: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2004: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2003: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Research Abstract |
We investigated the remnant pancreas after 90% pancreatectomy, PGP9.5 was strongly expressed in the pancreatic duct cells in the development and regenerating pancreas. So, PGP9.5 could be a possible marker of pancreatic progenitor cells. Based on these facts, we paid for our attention to the kinetics of endocrine cells in 24 hours after surgery, and demonstrated that pancreatic endocrine cells, but not acinar cells, positively stained for anti-PGP9.5 antibody. A few ductal cells were negative for pancreatic endocrine hormones and also for anti-PGP9.5 antibody during the very early stage (PGP9.5+, endocrine hormones-) and a few ductal cells positive for anti-PP antibody and anti-PGP9.5 antibody (PGP9.5+, PP+). A few cells appeared among acinar cells, too, which bore both insulin and amylase granules inside the cell.
We tried to clarify that whether these cells could be the progenitor to pancreatic endocrine cells or not, if these cells could be utilized for cell transplantation, and what
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a growth factor of the pancreatic beta cells was.
The results showed that there existed only few cells that stained positive for both anti-insulin and anti-amylase antibodies among acinar cells. This suggested that the acinar cells were unlikely to differentiate to beta cells. The ductal cells appearing during the very early stage were positively stained for anti-PGP9.5 antibody, but were not stained for anti-pancreatic endocrine hormone antibodies (PGP9.5+, endocrine hormones-or PP+), while those appearing 2 days after surgery positively stained for both antibodies (PGP9.5+, endocrine hormones+). Thus, the former cells were suggested to be the progenitor to pancreatic endocrine cells, because these cells were noted to differentiate to PGP9.5-positive and endocrine hormones-positive cells. However, the cells positive for both were rarely observed to appear. We also confirmed the fact that some beta cells had differentiated and proliferated from the centroacinar cells as well as anti-glucagon positive cells around the Langerhans islets 2 days after pancreatectomy. Also suggested was that the centroacinar cell was the most likely one among pancreatic duct cells as the progenitor to endocrine cells. As to the possibility of pancreatic endocrine cell or tissue transplantation, we inoculated pancreatic duct cells obtained after surgery under the renal fascia and found that those inoculated cells survived a certain period. However, we could not obtain any evidence that the inoculated cells effectively reduced the blood glucose level. Regarding a growth factor of pancreatic endocrine cells, we found that plasma cholecystkinin (CCK) level was increased after pancreatectomy, and was decreased by administration of CCK receptor antagonist (CCK-RA). The proliferation activity of both exocrine and endocrine cells was uniformly enhanced 5 days after the surgery, and the effect was inhibited by CCK-RA. These observations suggested that CCK acted as an important factor of pancreatic exocrine as well as endocrine regeneration.
Although there have been many experimental models on transplantation of pancreatic duct cells reported to date, the mechanisms of as well as the environmental factors for successful pancreatic duct cells transplantation remain to be resolved. Less
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