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US 2019/0290700 A1Published application
Derivation and self-renewal of isi1+ cells and uses thereof
AssigneeIsletone AB
InventorsKarl HENRIK-GRINNEMO, Oscar SIMONSON, Matthias CORBASCIO, Christer SYLVÉN, Eva WÄRDELL
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Abstract
The present invention relates to methods for deriving multipotent Isl1+ cells (i.e. methods for inducing a cell to enter a multipotent Isl1+ lineage), methods for differentiating Isl1+ cells to cardiac cells, cells obtainable by such methods, kits and compositions for carrying out the methods in accordance with the invention, and also medical applications and pharmaceutical compositions of said cells.
Claims12
1:
- A method for self-renewal of a multipotent Isl1+ cell, comprising the steps of:
- (i) culturing an Isl1+ cell in the presence of at least one laminin comprising an α5 chain, and in a medium comprising at least one agent which activates the Wnt canonical pathway;
- and,
- (ii) maintaining and/or expanding cells obtainable from step (i) in culture.
1 more element
2:
- The method according to claim 1, further comprising a differentiation step, wherein the differentiation step comprises culturing the Isl1+ cell in the presence of at least one laminin selected from the group comprising laminin 111, laminin 211, laminin 221, and any combination thereof.
3:
- A cell obtainable by the method of claim 1.
4:
- A composition comprising at least one laminin comprising an α5 chain and at least one agent which activates the Wnt canonical pathway.
5:
- The composition according to claim 4, wherein the at least one laminin comprising an α5 chain is selected from the group comprising laminin 511, laminin 521, and a combination of laminin 511 and laminin 521, and any synthetic, natural, or recombinant part or derivative or variant thereof.
6:
- The composition according to claim 4, wherein the composition is selected from the group comprising a liquid, a solid, a dispersion, a suspension, an emulsion, a microemulsion, a gel, or a solution, and any combination thereof.
7:
- A kit comprising at least one laminin comprising an α5 chain and a cell culture medium comprising at least one agent which activates the Wnt canonical pathway.
8:
- The kit according to claim 7, wherein the at least one laminin comprising an α5 chain is coated on a surface suitable for cell culture.
9:
- The kit according to claim 7, further comprising at least one laminin selected from the group comprising laminin 111, laminin 211, laminin 221, and any combination thereof, said at least one laminin preferably comprised in a separate container or on a separate surface suitable for cell culture.
10:
- The cell according to claim 3, for use in medicine.
11:
- The cell according to claim 3, for use in the treatment and/or prophylaxis of heart insufficiency, heart failure, myocardial infarction, and/or congenital heart disease due to cardiac defects affecting parts derived from the second heart field (for instance right atrium, right ventricle, outflow tracts (aorta, pulmonary arteries) and/or ventricular septum).
12:
- A pharmaceutical composition comprising the cell according claim 3 and at least one pharmaceutically acceptable excipient.