Study for developmental origin of mesenchymal blood cells and their regenerative activity in epidermolysis bullosa

2021 Fiscal Year Final Research Report

• Project/Area Number: 19H03682
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 53050:Dermatology-related
• Research Institution: Osaka University
• Principal Investigator: Tamai Katsuto 大阪大学, 医学系研究科, 寄附講座教授 (20236730)
• Co-Investigator(Kenkyū-buntansha): 新保 敬史 大阪大学, 医学系研究科, 特任准教授(常勤) (70780609)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 組織幹細胞 / 間葉系幹細胞 / 間葉球 / 表皮水疱症 / HMGB1

Outline of Final Research Achievements

Background: mesenchymal blood cells (MBCs), which are mobilized from bone marrow into the circulation by necrotic tissue-releasing nuclear protein HMGB1, contribute regeneration of the detached epithelia in the epidermolysis bullosa (EB), in which burn-like blistering occurs whole life by daily minor trauma. Aim: In this study, we explored developmental and in situ origins, and genetic markers for tracing cellular lineages of MBCs. We also tested effect of systemic HMGB1 peptide administration for cutaneous regeneration-induction in EB model mice. Results: We identified that MBCs are originated from neural fold/crest of ectoderm in embryonic ectoderm, and derived from Procr-positive PαS cells in bone marrow, and that systemic administration of MBC-mobilizing domain peptide of HMGB1 increases p63-positive epidermal stem cells in the skin of recessive dystrophic EB model mice, resulting in significant improvement of survival rate and induction of less-scar regeneration.

Free Research Field

皮膚科学、再生医学、遺伝子治療学、幹細胞医学

Academic Significance and Societal Importance of the Research Achievements

学術的意義：骨髄内や種々の組織内に間葉系幹細胞が存在すること、培養間葉系幹細胞移植で損傷組織の生成が促進されることが知られていたが、間葉系幹細胞の生体内存在意義については不明であった。本研究により、骨髄内の外胚葉性間葉系幹細胞は間葉球を産生し、生体内壊死組織の再生を誘導していることが明確に示された。
社会的意義：HMGB1のMBC誘導活性ドメインペプチド投与により損傷組織の再生と瘢痕抑制効果が得られることが示されたことから、現在国内製薬企業は本邦発・世界発の再生誘導医薬開発を進めている。