Stem cell composition
The disclosure provides stem cells which express high levels of Angeopoetin-1 (Ang1) and methods for their production. Such stem cells may be used in a range of therapeutic application.
1. A composition comprising a population of culture expanded genetically unmodified STRO-1+ mesenchymal precursor cells (MPC) wherein the culture expanded genetically unmodified MPCs express enhanced angiopoietin-1 (Ang1) in an amount between 0.1 μg/10 6 cells and 1.5 μg/10 6 cells.
2. The composition of claim 1 wherein said culture expanded genetically unmodified STRO-1+ MPCs express Ang1 in an amount between 0.5 μg/10 6 cells and 1.0 μg/10 6 cells.
3. The composition of claim 1 , wherein said culture expanded genetically unmodified STRO-1+ MPCs express Vascular Endothelial Growth Factor (VEGF) in an amount less than 0.05 μg/10 6 cells.
4. The composition of claim 1 , wherein said culture expanded genetically unmodified STRO-1+ MPCs express VEGF in an amount less than 0.03 μg/10 6 cells.
5. The composition of claim 3 , wherein said culture expanded genetically unmodified STRO-1+ MPCs express an increased Ang1:VEGF ratio relative to STRO-1+ MPCs that are not culture expanded at a ratio of between 2:1 and 30:1.
6. A composition according to claim 1 , wherein the culture expanded genetically unmodified Stro-1+ MPCs are obtained by a method which comprises:
(a) obtaining a cell population including genetically unmodified Stro-1+ MPCs from a donor; culturing the genetically unmodified STRO-1+ MPCs in vitro;
(b) determining the amount of Ang1 expressed by the genetically unmodified STRO-1+ MPCs in said cell population(s); and
(c) selecting genetically unmodified STRO-1+ MPCs which express Ang1 in an amount between 0.1 μg/10 6 cells and 1.5 μg/10 6 cells.
7. A composition according to claim 1 , wherein the culture expanded genetically unmodified Stro-1+ MPCs are produced by culture expanding a population of genetically unmodified STRO-1+ MPCs in vitro, wherein the culture expanding comprises: culturing a population of genetically unmodified MPCs in a cell culture medium, wherein the cell culture medium contains a short acting L-ascorbic acid derivative but does not contain a substantial amount of a long acting L-ascorbic acid derivative; and/or is supplemented with less than 10% v/v fetal calf serum (FCS); and/or is supplemented with non fetal serum,
wherein a short acting L-ascorbic acid derivative is an L-ascorbic acid derivative that is oxidised by approximately 80-90% following 24 hours of cell culture under culture conditions of neutral pH and 37° C.; and
a long acting L-ascorbic acid derivative is an L-ascorbic acid derivative that is not oxidised by approximately 80-90% following 24 hours of cell culture under culture conditions of neutral pH and 37° C.
8. A composition according to claim 1 , wherein the culture expanded genetically unmodified STRO-1+ MPCs are culture expanded in a culture medium which:
(a) comprises a short acting L-ascorbic acid derivative but does not contain a substantial amount of long acting L-ascorbic acid derivative;
(b) is supplemented with less than 10% v/v fetal calf serum (FCS); and/or
(c) is supplemented with non-fetal serum,
wherein a short acting L-ascorbic acid derivative is an L-ascorbic acid derivative that is oxidised by approximately 80-90% following 24 hours of cell culture under culture conditions of neutral pH and 37° C.; and
a long acting L-ascorbic acid derivative is an L-ascorbic acid derivative that is not oxidised by approximately 80-90% following 24 hours of cell culture under culture conditions of neutral pH and 37° C.