Study for developmental origin of mesenchymal blood cells and their regenerative activity in epidermolysis bullosa
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
|
Project Status |
Completed (Fiscal Year 2021)
|
Budget Amount *help |
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2021: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥9,230,000 (Direct Cost: ¥7,100,000、Indirect Cost: ¥2,130,000)
|
Keywords | 組織幹細胞 / 間葉系幹細胞 / 間葉球 / 表皮水疱症 / HMGB1 / 外胚葉性間葉系細胞 / 間葉・上皮転換 / 幹細胞再生医学 |
Outline of Research at the Start |
研究の概要
表皮水疱症患者皮膚は生直後より繰り返す表皮剥離により表皮幹細胞を喪失しているにもかかわらず、表皮再生能を維持している。研究代表者は骨髄由来間葉系細胞と壊死表皮のクロストークによる表皮再生メカニズムを世界に先駆けて報告した。本研究は、表皮水疱症剥離表皮の再生能を持つ末梢循環性間葉系細胞(mesenchymal blood cell、MBC)の発生学的起源を探索するとともに、1細胞レベルでの網羅的トランスクリプトーム解析技術、網羅的エピゲノム解析技術を用いて間葉系細胞から表皮細胞への分化転換に関わる分子基盤を解明し、表皮幹細胞再生医学領域を開拓する。
|
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.
|
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。
|
Report
(4 results)
Research Products
(39 results)
-
-
[Journal Article] Longitudinal Single-Cell Transcriptomics Reveals a Role for Serpina3n-Mediated Resolution of Inflammation in a Mouse Colitis Model.2021
Author(s)
Ho YT, Shimbo T, Wijaya E, Kitayama T, Takaki S, Ikegami K, Miyashita K, Ouchi Y, Takaki E, Yamamoto R, Kaneda Y, Tamai K
-
Journal Title
Cell Mol Gastroenterol Hepatol
Volume: 12(2)
Issue: 2
Pages: 547-566
DOI
Related Report
Peer Reviewed / Open Access
-
-
[Journal Article] Synthesized HMGB1 peptide attenuates liver inflammation and suppresses fibrosis in mice.2021
Author(s)
Nojiri S, Tsuchiya A, Natsui K, Takeuchi S, Watanabe T, Kojima Y, Watanabe Y, Kamimura H, Ogawa M, Motegi S, Iwasawa T, Sato T, Kumagai M, Ishii Y, Kitayama T, Li YT, Ouchi Y, Shimbo T, Takamura M, Tamai K, Terai S
-
Journal Title
Inflamm Regen
Volume: 41(1)
Issue: 1
Pages: 28-28
DOI
Related Report
Peer Reviewed / Open Access
-
-
-
-
-
[Journal Article] Consensus re-classification of inherited epidermolysis bullosa and other disorders with skin fragility.2020
Author(s)
Has C, Bauer JW, Bodemer C, Bolling M, Bruckner-Tuderman L, Diem A, Fine JD, Heagerty A, Hovnanian A, Marinkovich P, Martinez AE, McGrath JA, Moss C, Murrell DF, Palisson F, Schwieger-Briel A, Sprecher E, Tamai K, Uitto J, Woodley DT, Zambruno G, Mellerio JE
-
Journal Title
Br J Dermatol
Volume: 183(4)
Issue: 4
Pages: 614-627
DOI
Related Report
Peer Reviewed / Open Access
-
-
-
-
-
-
[Journal Article] Bone marrow transplant with post-transplant cyclophosphamide for recessive dystrophic epidermolysis bullosa expands the related donor pool and permits tolerance of nonhaematopoietic cellular grafts.2019
Author(s)
Ebens CL, McGrath JA, Tamai K, Hovnanian A, Wagner JE, Riddle MJ, Keene DR, DeFor TE, Tryon R, Chen M, Woodley DT, Hook K, Tolar J
-
Journal Title
Br J Dermatol
Volume: 181
Issue: 6
Pages: 1238-1246
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-