Stem cell composition

Patent metadata

Field	Value
Publication number	US-10400218-B2
Application number	US-201515300716-A
Country	US
Kind code	B2
Filing date	Apr 7, 2015
Priority date	Apr 7, 2014
Publication date	Sep 3, 2019
Grant date	Sep 3, 2019

Abstract

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.

First claim

The invention claimed is:

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.

Assignees

• Mesoblast Int Sarl

Inventors

• Itescu Silviu
• Simmons Paul

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P7/02

  Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors · CPC title

• C12N2501/39

  Steroid hormones · CPC title