論文 - 詳細
| RRC ID | 67177 |
|---|---|
| 著者 | Nakayama C, Fujita Y, Matsumura W, Ujiie I, Takashima S, Shinkuma S, Nomura T, Abe R, Shimizu H. |
| タイトル | The development of induced pluripotent stem cell-derived mesenchymal stem/stromal cells from normal human and RDEB epidermal keratinocytes. |
| ジャーナル | J Dermatol Sci |
| Abstract |
BACKGROUND:Epidermolysis bullosa (EB) is a group of hereditary disorders caused by mutations in the genes encoding structural molecules of the dermal-epidermal junction (DEJ). Cell-based therapies such as allogeneic mesenchymal stem/stromal cell (MSC) transplantation have recently been explored for severe EB types, such as recessive dystrophic EB (RDEB). However, hurdles exist in current MSC-based therapies, such as limited proliferation from a single cell source and limited cell survival due to potential allogenic rejection. OBJECTIVES:We aimed to develop MSCs from keratinocyte-derived induced pluripotent stem cells (iPSCs). METHODS:Keratinocyte-derived iPSCs (KC-iPSCs) of a healthy human and an RDEB patient were cultured with activin A, 6-bromoindirubin-3'-oxime and bone morphogenetic protein 4 to induce mesodermal lineage formation. These induced cells were subjected to immunohistochemical analysis, flow cytometric analysis and RNA microarray analysis in vitro, and were injected subcutaneously and intravenously to wounded immunodeficient mice to assess their wound-healing efficacy. RESULTS:After their induction, KC-iPSC-induced cells were found to be compatible with MSCs. Furthermore, with the subcutaneous and intravenous injection of the KC-iPSC-induced cells into wounded immunodeficient mice, human type VII collagen was detected at the DEJ of epithelized areas. CONCLUSIONS:We successfully established iPSC-derived MSCs from keratinocytes (KC-iPSC-MSCs) of a normal human and an RDEB patient. KC-iPSC-MSCs may have potential in therapies for RDEB. |
| 巻・号 | 91(3) |
| ページ | 301-310 |
| 公開日 | 2018-9-1 |
| DOI | 10.1016/j.jdermsci.2018.06.004 |
| PII | S0923-1811(18)30247-0 |
| PMID | 29933899 |
| MeSH | Aged Animals Case-Control Studies Cell Lineage* Cell Separation / methods Cells, Cultured Collagen Type VII / metabolism Disease Models, Animal Epidermolysis Bullosa Dystrophica / genetics Epidermolysis Bullosa Dystrophica / metabolism Epidermolysis Bullosa Dystrophica / pathology* Female Humans Induced Pluripotent Stem Cells / drug effects Induced Pluripotent Stem Cells / metabolism Induced Pluripotent Stem Cells / pathology* Induced Pluripotent Stem Cells / transplantation Keratinocytes / drug effects Keratinocytes / metabolism Keratinocytes / pathology* Keratinocytes / transplantation Mesenchymal Stem Cell Transplantation Mesenchymal Stem Cells / drug effects Mesenchymal Stem Cells / metabolism Mesenchymal Stem Cells / pathology* Mice, Inbred C57BL Mice, Inbred NOD Mice, SCID Middle Aged Phenotype Skin / drug effects Skin / metabolism Skin / pathology* Wound Healing Wounds, Penetrating / metabolism Wounds, Penetrating / pathology Wounds, Penetrating / surgery |
| IF | 3.681 |
| リソース情報 | |
| ヒト・動物細胞 | 201B7(HPS0063) |