The co-transplantation of Islets with Dental Pulp Stem Cells Improved Survival and Function of Transplanted Beta-Cells

Research Project

Project/Area Number	16K09742
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Metabolomics
Research Institution	Aichi Medical University
Principal Investigator	Tsunekaewa Shin 愛知医科大学, 医学部, 准教授 (40612768)
Co-Investigator(Kenkyū-buntansha)	山本朗仁徳島大学, 大学院医歯薬学研究部(歯学域), 教授 (50244083) 清野祐介藤田医科大学, 医学部, 講師 (80534833)
Project Period (FY)	2016-04-01 – 2019-03-31
Project Status	Completed (Fiscal Year 2018)
Budget Amount *help	¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000) Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000) Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000) Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords	糖尿病 / 膵島移植 / 組織幹細胞 / 移植・再生医療
Outline of Final Research Achievements	We examined the effect of co-transplantation of islets with Dental pulp stem cells from human exfoliated deciduous teeth (SHED) on glycemic control in streptozotocin diabetic mice to protect the viability of transplanted islets in the recipient. The co- SHED treatment reduced blood glucose levels in streptozotocin-diabetic mice. Co- SHED treatment groups preserved the insulin content of transplanted islets in the kidney capsule more than the islets-alone treatment group. Co- SHED transplantation histologically improved the islet engraftment, although this result is still only a preliminary study. SHED had beneficial effects in paracrine manner on insulin secretion of isolated pancreatic islets. This study demonstrated that co-transplantation of islets with SHED had a beneficial effect on the survival of transplanted islets than transplantation of islets alone and has a potential as a practical strategy for T1DM treatment.
Academic Significance and Societal Importance of the Research Achievements	致死的低血糖を繰り返しインスリン注射のみでは治療困難な1型糖尿病治療のため、侵襲の少ない膵島移植が近年行われている。しかし、膵島移植後のインスリン離脱率は侵襲の大きな膵臓移植に比べ低い。その原因として単離され移植された膵島は、豊富な血管と神経組織がないため、膵臓移植に比べ生着率が低いため考えられる。また、膵島移植ではインスリン離脱するには複数ドナーからの単離膵島量が必要となるため、ドナー数の少ないわが国での膵島移植症例は欧米に比べ圧倒的に少ない。本研究で得られたヒト歯髄幹細胞による移植膵島の保護的な作用は、膵島移植の治療成績を上げ、ドナー数の少ないわが国でその普及を広げ得る可能性を示した。