Elucidation of mesenchymal to epithelial transition mechanism of bone marrow mesenchymal stem cells and application to regenerative medicine.
| Project/Area Number |
22390217
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Dermatology
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| Research Institution | Osaka University |
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Principal Investigator |
TAMAI Katsuto 大阪大学, 医学系研究科, 寄附講座教授 (20236730)
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| Project Period (FY) |
2010 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥18,980,000 (Direct Cost: ¥14,600,000、Indirect Cost: ¥4,380,000)
Fiscal Year 2012: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2011: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2010: ¥10,140,000 (Direct Cost: ¥7,800,000、Indirect Cost: ¥2,340,000)
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| Keywords | 骨髄間葉系幹細胞 / 間葉上皮転換(MET) / HMGB1 / CXCL12 / CXCR4 / 間葉系幹細胞 / 表皮水疱症 / VII型コラーゲン / SDF-1α / 間葉-上皮転換 / SSEA3 / ケラチン5 / 再生誘導 / 皮膚損傷 |
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| Research Abstract |
Previously, we had shown that bone marrow-derived mesenchymal stem/progenitor cells contribute regeneration of detached epithelia in the skin of epidermolysis bullosa (EB), a intractable genetic skin disease. With such background, in this study, we aimed to investigate precise mechanism of mesenchymal to epithelial transition (MET) of bone marrow-derived mesenchymal cells in the EB skin, and to apply the obtained results for developing novel regenerative medicine. In 2012, we found that injured epithelia of EB skin release abundant high mobility group box 1 (HMGB1) to stimulate and mobilize lineage-/PDGFR.+/c-kit- (L-P+K-) bone marrow cells into the circulation, and the circulating L-P+K- cells are then accumulate to the injured skin via CXCR4/SDF-1. axis to provide bone marrow-derived epithelial cells by MET. In 2013, we further investigated particular cell surface marker for identifying MET-capable cell in L-P+K- population, and clarified that SSEA3 is an exclusive maker for specifically identifying the MET-capable cells in the L-P+K- cell population. We also proved that L-P+K- bone marrow-derived cells are essential for regeneration of EB skin by blocking accumulation of those cells by systemic inoculating CXCR4 antagonist in EB mouse model, resulting in persistent severe cutaneous injury. In 2014, we examined efficacy of systemic administration of HMGB1 on regeneration processes of cutaneous injury, and found that HMGB1 administration significantly accelerate tissue regeneration by inducing accumulation of L-P+K- cells in the injury, which then provide potent anti-inflammatory molecules and regenerate the injured epithelia by MET.
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Report
(4 results)
Research Products
(71 results)
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[Journal Article] Systemic Circulation and Bone Recruitment of Osteoclast Precursors Tracked by Using Fluorescent Imaging Techniques.2013
Author(s)
Kotani M, Kikuta J, Klauschen F, Chino T, Kobayashi Y, Yasuda H, Tamai K, Miyawaki A, Kanagawa O, Tomura M, Ishii M
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Journal Title
J Immunol
Volume: 190(2)
Pages: 605-612
Related Report
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[Journal Article] HIG1, a novel regulator of mitochondrial γ-secretase, maintains normal mitochondrial function.2012
Author(s)
Hayashi H, Nakagami H, Takeichi M, Shimamura M, Koibuchi N, Oiki E, Sato N, Koriyama H, Mori M, Gerardo Araujo R, Maeda A, Morishita R, Tamai K, Kaneda Y
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Journal Title
FASEB J
Volume: 26(6)
Pages: 2306-2317
Related Report
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[Journal Article] Two cases of recessive dystrophic epidermolysis bullosa diagnosed as severe generalized.2012
Author(s)
Ohashi M, Shu E, Nagai M, Murase K, Nakano H, Tamai K, Sawamura D, Hiroka T, Seishima M, Kitajima Y, Aoyama Y
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Journal Title
J Dermatol
Volume: 38
Pages: 893-9
NAID
Related Report
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[Journal Article] Systemic Circulation and Bone Recruitment of Osteoclast Precursors Tracked by Using Fluorescent Imaging Techniques.2012
Author(s)
Kotani M, Kikuta J, Klauschen F, Chino T, Kobayashi Y, Yasuda H, Tamai K, Miyawaki A, Kanagawa O, Tomura M, Ishii M
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Journal Title
J Immunol.
Volume: Epub ahead of print
Related Report
Peer Reviewed
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[Journal Article] Two cases of recessive dystrophic epidermolysis bullosa diagnosed as severe generalized.2012
Author(s)
Ohashi M, Shu E, Nagai M, Murase K, Nakano H, Tamai K, Sawamura D, Hiroka T, Seishima M, Kitajima Y, Aoyama Y.
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Journal Title
J Dermatol
Volume: 38
Pages: 893-899
NAID
Related Report
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[Journal Article] PDGFR.-positive cells in bone marrow are mobilized by HMGB1 to regenerate injured epithelia.2011
Author(s)
Tamai K, Yamazaki T, Chino T, Ishii M, Otsuru S, Kikuchi Y, Iinuma S, Saga K, Nimura K, Shimbo T, Umegaki N, Katayama I, Miyazaki J, Takeda J, McGrath JA, Uitto J, Kaneda Y
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Journal Title
Proc Natl Acd Sci USA
Volume: 108
Pages: 6609-6614
Related Report
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[Journal Article] Modification of a novel angiogenic peptide, AG30, for the development of novel therapeutic agents.2011
Author(s)
Nakagami H, Nishikawa T, Tamura N, Maeda A, Hibino H, Mochizuki M, Shimosato T, Moriya T, Morishita R, Tamai K, Tomono K, Kaneda Y
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Journal Title
Journal of Cellular and Molecular Medicine
Volume: -
DOI
Related Report
Peer Reviewed
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[Journal Article] PDGFRα-positive cells in bone marrow are mobilized by HMGB1 to regenerate injured epithelia2011
Author(s)
Tamai K, Yamazaki T, Chino T, Ishii M, Otsuru S, Kikuchi Y, Iinuma S, Saga K, Nimura K, Shimbo T, Umegaki N, Katayama I, Miyazaki J, Takeda J, McGrath JA, Uitto J, Kanda Y
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Journal Title
Proc Natl Acd Sci USA
Volume: 108
Pages: 6609-6614
Related Report
Peer Reviewed
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[Journal Article] Two cases of recessive dystrophic epidermolysis bullosa diagnosed as severe generalized2011
Author(s)
Ohashi M, Shu E, Nagai M, Murase K, Nakano H, Tamai K, Sawamura D, Hiroka T, Seishima M, Kitajima Y, Aoyama Y
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Journal Title
J Dermatol
Volume: 38
Pages: 893-839
NAID
Related Report
Peer Reviewed
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[Journal Article] Relation between the expression of level of the POU transcription factor Skn-1a and Skn-1n and keratinocyte differentiation.2010
Author(s)
Takemoto H, Tamai K, Akasaka E, Rokunohe D, Takiyoshi N, Umegaki N, Nakajima K, Aizu T, Kaneko T, Nakano H, Sawamura D
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Journal Title
J Dermatol Sci
Volume: 60
Pages: 203-205
NAID
Related Report
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[Journal Article] Relation between expression levels of the POU transcriptional factor Skn-1a and Skn-1n and keratinocyte differentiation.2010
Author(s)
Takemoto H, Tamai K, Akasaka E, Rokunohe D, Takiyoshi N, Umegaki N, Nakajima K, Aizu T, Kaneko T, Nakano H, Sawamura D.
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Journal Title
J Dermatol Sci
Volume: 60
Pages: 203-205
NAID
Related Report
Peer Reviewed
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