Development of a radical therapy for diabetic ulcer focusing on mesenchymal cells in adipose tissue

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K18908
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56070:Plastic and reconstructive surgery-related
• Research Institution: Sapporo Medical University
• Principal Investigator: Kita Arisa 札幌医科大学, 医学部, 助教 (20642185)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 細胞老化 / SASP / 脂肪 / 糖尿病性潰瘍 / 創傷治癒

Outline of Final Research Achievements

Diabetic ulcers are prone to recurrence and are intractable. Bone marrow mesenchymal stem cells and adipose progenitor cells are known to be impaired in diabetic patients. In this study, we focused on cellular senescence in mesenchymal cells in subcutaneous fat as a cause for this. The results showed that during the wound healing process in diabetic mice and humans, cellular senescence did not occur at the timing that occurs normally, but senescent cells accumulated in the late stages of wound healing. Membrane antibody array analysis of secreted factors of senescent cells showed that CCL-11, MMP-3, and other factors were increased in diabetic mice and inhibited fibroblast proliferation. These results suggest that abnormalities of senescent cells may be involved in impaired wound healing of diabetic ulcers.

Free Research Field

細胞老化、糖尿病性潰瘍、創傷治癒

Academic Significance and Societal Importance of the Research Achievements

本研究により、皮下脂肪における細胞老化の異常が糖尿病性潰瘍に関与していることが明らかになった。細胞老化に介入して創傷治癒を促進するという新しい治療戦略は、難治性であり肢切断のリスクもある糖尿病性潰瘍に、より根治的な治癒をもたらす可能性があり、社会的意義は非常に大きい。また、糖尿病性潰瘍に関する研究では皮膚の異常に着目するものが多い中で、脂肪組織に焦点を当てたことが本研究の特色である。脂肪組織は皮下や内臓周囲、骨髄内など全身に分布している。脂肪組織における細胞老化の異常性を明らかにすることで、糖尿病性潰瘍のみならず、慢性炎症によって生じる様々な疾患に対する新しい治療法の開発に繋がると考えている。