Method of determining or influencing the chondrogenic potential of mesenchymal stromal cells
AssigneeAo Technology AG
InventorsMartin Stoddart, Mauro Alini
Life of this patent
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Abstract
A method of increasing the chondrogenic potential mediated by TGFβ of a mesenchymal stromal cell (MSC) or a population of mesenchymal stromal cells (MSCs), comprising the step of increasing the amount of TGFβR1, and/or decreasing the amount of TGFβR2, and/or decreasing the amount of and/or ACVRL1 of the MSC or a population of mesenchymal stromal cells (MSCs).
Claims23
A method of increasing the chondrogenic potential mediated by Transforming Growth Factor Beta Receptors (TGFβR) of a mesenchymal stromal cell (MSC) or a population of mesenchymal stromal cells (MSCs), comprising the steps of:
- increasing the amount of Transforming Growth Factor Beta Receptor 1 (TGFβR1), and decreasing the amount of Transforming Growth Factor Beta Receptor 2 (TGFβR2),
- wherein the amount of TGFβR1 is increased by promoting the expression of TGFβR1, and the amount of TGFβR2 is decreased by at least partially inhibiting the expression of TGFβR2,
- wherein the amount of TGFβR1 of the MSC or the population of MSCs is increased and the amount of TGFβR2 of the MSC or the population of MSCs is decreased such that the ratio between TGFβR1 and TGFβR2 of the MSC or the population of MSCs is within the range of 0.12 to 0.6.
A method of identifying a mesenchymal stromal cell (MSC) or a population of mesenchymal stromal cells (MSCs) exhibiting an increased chondrogenic potential mediated by Transforming Growth Factor Beta Receptors (TGFβR), comprising the steps of
- a. determining a first value reflective of the amount of Transforming Growth Factor Beta Receptor 1 (TGFβR1) of said MSC or said population of MSCs, respectively;
- b. determining a second value reflective of the amount of Transforming Growth Factor Beta Receptor 2 (TGFβR2), of the MSC or population of MSCs, respectively;
- c. calculating the ratio between the first value and the second value;
- d. determining if said ratio is within the range of 0.12 to 0.6;
- and if so,
- e. identifying said MSC or population of MSCs as an MSC or population of MSCs, respectively, exhibiting an increased chondrogenic potential mediated by TGFβ.
A method of committing a mesenchymal stromal cell (MSC) or a population of mesenchymal stromal cell (MSCs) to further differentiation in the chondrocytic lineage, comprising the steps of
- a. providing a mesenchymal stromal cell (MSC) or a population of mesenchymal stromal cells (MSCs),
- b. increasing the amount of Transforming Growth Factor Beta Receptor 1 (TGFβR1) and decreasing the amount of Transforming Growth Factor Beta Receptor 2 (TGFβR2) of the mesenchymal stromal cell (MSC) or of the population of mesenchymal stromal cells (MSCs) such that the ratio between TGFβR1 and TGFβR2 of the MSC or the population of MSCs is within the range of 0.12 to 0.6,
- c. contacting the mesenchymal stromal cell (MSC) or the population of mesenchymal stromal cells (MSCs) having an increased amount of TGFβR1, and a decreased amount of TGFβR2, with an effective amount of TGFβ, such as to commit said MSC to further differentiation in the chondrocytic lineage.
The method according 10, wherein additionally, the amount of ACVRL1 is decreased to about 10% or less of the initial amount of ACVRL1 in the MSC or populations of MSCs.
Dependencies are inferred from the claim text.