Critical role of HGF/c-Met signaling pathway in islet transplantation

2018 Fiscal Year Final Research Report

• Project/Area Number: 15K10178
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Asahikawa Medical College
• Principal Investigator: KAWAHARA TOSHIYASU 旭川医科大学, 医学部, 講師 (60407260)
• Co-Investigator(Kenkyū-buntansha): 松野 直徒 旭川医科大学, 医学部, 特任教授 (00231598) ; 古川 博之 旭川医科大学, 医学部, 教授 (70292026)
• Project Period (FY): 2015-04-01 – 2019-03-31
• Keywords: 膵島移植

Outline of Final Research Achievements

The aim of this study is to inhibit cell-death of transplanted islet cells in the livers by stimulation of HGF/cMet signaling pathway in vitro using recombinant HGF.We performed total pancreatectomy of 17 pigs to induce permanent diabetes as a model of type 1 diabetes. Despite of total pancreatectomy, blood glucose levels returned to normal 2 week after total pancreatectomy, probably due to residual pancreas around inferior vena cava (IVC). Since it was high risk to remove the residual pancreas surgically around IVC, we used streptozotocin to inhibit the function of residual pancreas after total pancreatectomy. However, unfortunately blood glucose levels came back to normal.
We did not have enough time to clarify the role of HGF/cMet signaling pathway in islet transplantation.

Free Research Field

消化器外科　移植外科

Academic Significance and Societal Importance of the Research Achievements

膵島移植は、1型糖尿病に対する低侵襲かつ根治的治療であります。その一方で肝臓内に移植した膵島細胞の多くは細胞死してしまい機能しなくなる現実を克服すべく、リコンビナントHGF刺激により細胞死に耐えうる膵島を作成しようと試みました。残念ながら大動物の実験モデル作成に難渋し、結果を出すに至りませんでしたが、今後はiPS細胞などの出現によりさらなるこの分野の発展が期待されております。