Deciphering the aging mechanism directed by exosomes in the adult progeria Werner syndrome

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K16542
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52010:General internal medicine-related
• Research Institution: Chiba University
• Principal Investigator: Kato Hisaya 千葉大学, 医学部附属病院, 助教 (90841974)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: 早老症 / 老化 / ウェルナー症候群 / 間葉系幹細胞 / iPS細胞

Outline of Final Research Achievements

Werner syndrome (WS) is an autosomal recessive premature aging disorder that causes gray hair, hair loss, cataracts, diabetes, dyslipidemia, atherosclerotic disease, and malignant tumors from a young age. WS patients are also characterized by calcification of Achilles tendons and soft tissues and intractable skin ulcers, but no fundamental treatment has yet been established. Abnormalities of mesenchymal stem cells (MSCs) are suspected to be responsible for these symptoms, but the effect of WS-derived MSCs on skin ulcers is unknown. In this study, iPS cells derived from WS patients were differentiated into MSCs and injected into mouse models of skin ulcers, and we found that WS-MSCs have inferior wound-healing ability compared to healthy MSCs. Additionally, the wound healing ability of WS-MSCs was improved by mixed administration with VEGF. These findings are expected to be applied to the elucidation of pathological conditions and therapeutic applications in the future.

Free Research Field

老化

Academic Significance and Societal Importance of the Research Achievements

本研究では、ウェルナー症候群患者から樹立したiPS細胞から分化させた間葉系幹細胞が、早期細胞老化を示すこと、分泌因子に異常をきたすこと、中でも血管新生に大きな影響を持つVEGFの異常が疑われることを明らかにした。VEGFとウェルナー症候群間葉系幹細胞の混合投与が難治性皮膚潰瘍モデルマウスの創傷治癒を促進させたことから、分泌因子を中心とした病態メカニズムやこれらをターゲットとした治療応用へと発展させることが期待できる。