An effective differentiation protocol of insulin producing cells from adipose derived stem cells with Nrf2 inducer

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K16281
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55010:General surgery and pediatric surgery-related
• Research Institution: The University of Tokushima
• Principal Investigator: SAITO Yu 徳島大学, 病院, 特任助教 (50548675)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Keywords: Nrf2 inducer / 間葉系幹細胞 / インスリン産生細胞

Outline of Final Research Achievements

The aim of this study was to investigate the effectiveness of 3D culture system with Nrf2 inducer on differentiation of human ADSCs to functional IPCs. EGCG was used as Nrf2 inducer. EGCG was added into Step 1 (germ layer conversion), Step 2 (IPC maturation), and Step 1/2. In terms with dose of EGCG, we have previously reported the islet protective effect of EGCG with 100uM dose (Surgery Today 2019), and that dose was also chosen in this study.
As a result, EGCG addition (100uM) decreased cell viabilities and insulin secretary function of IPCs. 100uM was thought to be cytotoxic for IPC differentiation. A low dose EGCG (10uM) also did not stimulate IPCs differentiation from ADSCs in both germ layer conversion and maturation steps.In conclusion, Nrf2 inducer, EGCG, did not stimulate IPC differentiation from ADSC. Further investigations were necessary to examine the EGCG effect for IPC differentiation.

Free Research Field

再生医療

Academic Significance and Societal Importance of the Research Achievements

MSCは中胚葉性組織（間葉）に由来する体性幹細胞であり、通常は間葉系に属する細胞へと分化するが、微小環境の変化により中胚葉性でない組織にまで分化可能である。これまでに、MSCにNrf2を過剰発現させることで、骨芽細胞への分化誘導を促進することが報告されている。Nrf2 inducerが、MSCからIPCへの分化誘導の促進することで、低侵襲かつ迅速に移植が可能となり得ると考えられる。