The development of induced pluripotent stem cell-derived mesenchymal stem/stromal cells from normal human and RDEB epidermal keratinocytes
| Autor: | Hiroshi Shimizu, Yasuyuki Fujita, Toshifumi Nomura, Wakana Matsumura, Inkin Ujiie, Shota Takashima, Satoru Shinkuma, Chihiro Nakayama, Riichiro Abe |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Keratinocytes
0301 basic medicine Collagen Type VII Stromal cell Induced Pluripotent Stem Cells Cell Wounds Penetrating Cell Separation Mice SCID Dermatology Mesenchymal Stem Cell Transplantation Biochemistry 03 medical and health sciences 0302 clinical medicine Mice Inbred NOD medicine Animals Humans Cell Lineage Induced pluripotent stem cell Molecular Biology Cells Cultured Aged Skin Wound Healing business.industry Mesenchymal stem cell Mesenchymal Stem Cells Middle Aged medicine.disease In vitro Epidermolysis Bullosa Dystrophica Mice Inbred C57BL Transplantation Disease Models Animal Phenotype 030104 developmental biology medicine.anatomical_structure Bone morphogenetic protein 4 Case-Control Studies 030220 oncology & carcinogenesis Cancer research Female Epidermolysis bullosa business |
| Zdroj: | Journal of Dermatological Science. 91:301-310 |
| ISSN: | 0923-1811 |
| DOI: | 10.1016/j.jdermsci.2018.06.004 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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