Systemic sclerosis disease model and use thereof
AssigneeYiPSCELL Inc.
InventorsJi Hyeon JU, Ye Na KIM
Life of this patent
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Abstract
The present invention relates to a production method of a systemic sclerosis disease model using keratinocytes and fibroblasts differentiated from induced pluripotent stem cells derived from patients with systemic sclerosis, a systemic sclerosis disease model produced thereby, and a method for screening a therapeutic agent for systemic sclerosis using the same. The systemic sclerosis disease model produced by the above production method can be effectively used for preventing or treating systemic sclerosis.
Claims16
(canceled)
A method for producing a systemic sclerosis disease model, comprising:
- a step of differentiating induced pluripotent stem cells (iPSC) derived from patients with systemic sclerosis (SSc) into keratinocytes or fibroblasts;
- a step of forming a 3D skin organoid by three-dimensionally culturing the keratinocytes or fibroblasts;
- and
- a step of transplanting the 3D skin organoid into the skin tissue of a mouse,
- wherein the skin thickness of the mouse transplanted with the 3D skin organoid is increased compared to normal mice.
(canceled)
A method for differentiating induced pluripotent stem cells into keratinocytes, comprising:
- a step of primarily culturing an embryonic body (EB) of induced pluripotent stem cells (iPSC) derived from patients with systemic sclerosis (SSc) in Differentiation Culture Medium 1 comprising DMEM/F12 for 3 to 10 days;
- a step of secondarily culturing for 2 to 10 days by replacing the culture medium with Differentiation Culture Medium 2 comprising a defined keratinocyte serum-free medium (DKSFM);
- and
- a step of tertiarily culturing for 5 to 60 days by replacing the secondary culture medium with Differentiation Culture Medium 3 comprising DKSFM and a keratinocyte serum-free medium (KSFM).
A method for differentiating induced pluripotent stem cells into fibroblasts, comprising:
- a step of culturing an embryonic body (EB) of induced pluripotent stem cells (iPSC) derived from patients with systemic sclerosis (SSc) in Differentiation Culture Medium 1 comprising DMEM/F12 and epidermal growth factor (EGF) for 1 to 7 days;
- a step of maintaining for 1 to 7 days by adding BMP4 to the Differentiation Culture Medium 1;
- a step of secondarily culturing for 5 to 15 days by replacing the culture medium with Differentiation Culture Medium 2 comprising DMEM/F12 thereafter;
- and
- a step of tertiarily culturing for 5 to 20 days by replacing the culture medium with Differentiation Culture Medium 1 thereafter.
10-11. (canceled)
A fibroblast derived from induced pluripotent stem cells, wherein the fibroblast is a fibroblast derived from induced pluripotent stem cells from patients with systemic sclerosis in which the expression of a fibrosis marker is increased, compared to a fibroblast derived from normal induced pluripotent stem cells, and
- wherein the fibrosis marker comprises one or more selected from the group consisting of COL1A1, COL1A2, COL3A1, ACTA2, and vimentin.
15-16. (canceled)
A systemic sclerosis disease model, comprising a 3D cell aggregate formed by culturing induced pluripotent stem cells (iPSC) derived from patients with systemic sclerosis (SSc), wherein the cell aggregate exhibits a pathological property of systemic sclerosis, and
- wherein the pathological property of cells exhibits increased cell proliferation and the increased production and accumulation of fibrosis markers and collagen, compared to normal induced pluripotent stem cells.
18-22. (canceled)
Dependencies are inferred from the claim text.