Method to improve therapeutic properties of stem cells
In one aspect, a method of preconditioning stem cells comprising exposing stem cells to low dose radiation (LDR) is provided. In another aspect, a population of preconditioned stem cells is provided, wherein the population of 5 preconditioned stem cells is obtained by exposing stem cells to LDR. Uses of the preconditioned stem cells are also provided. In other aspects, the stem cells are muscle stem cells.
1 . A population of preconditioned muscle stem cells, wherein the population of preconditioned muscle stem cells is obtained by using a method of preconditioning muscle stem cells, the method comprising:
a. providing a sample comprising a plurality of target muscle stem cells;
b. irradiating the target muscle stem cells with a low dose of radiation comprising between 10 and 100 mGy of radiation emitted from a radiation source during an irradiation period to convert the target muscle stem cells to irradiated, preconditioned muscle stem cells suitable for use in a subsequent therapeutic treatment process;
wherein irradiating the target muscle stem cells reduces age-associated decline of at least a first cellular function of each target muscle stem cell.
2 . The population of claim 1 , wherein the first cellular function has an initial performance value and defines an aged performance value at a threshold aging time, and wherein the preconditioned stem cells have a treated performance value at the threshold aging time that is between the aged performance value and the initial performance value.
3 . The population of claim 2 , wherein the first cellular function is cellular fusion, the initial performance value comprises an initial fusion index, the aged performance value comprises an aged fusion index, and the treated performance value comprises a treated fusion index, wherein the treated fusion index is greater than the aged fusion index.
4 . The population of claim 3 , wherein the treated fusion index is at least twice the aged fusion index.
5 . The population of claim 3 , wherein the preconditioned muscle stem cells show increased differentiation into muscle fibers compared to target muscle stem cells that are not irradiated.
6 . The population of claim 3 , wherein the preconditioned muscle stem cells have higher expression of at least one marker selected from the group consisting of myogenin, MyH3, MyoD, TKS5 and TMEM8c compared to target muscle stem cells that are not irradiated.
7 . The population of claim 1 , wherein the radiation comprises low linear energy transfer (LET) ionizing radiation and comprises γ-radiation.
8 . The population of claim 1 , wherein the dose of radiation is 10 mGy.
9 . The population of claim 1 , wherein first dose of radiation is 50 mGy.
10 . The population of claim 1 , wherein first dose of radiation is 100 mGy.
11 . The population of claim 1 , wherein the population is for use in a subsequent therapeutic process comprising administering the population to a subject in need thereof.
12 . The population of claim 11 , wherein the subject is a human.
13 . The population of claim 11 , wherein the subject has a muscle disease.
14 . The population of claim 1 , wherein the treated fusion index is more than 60%.
15 . The population of claim 1 , wherein the preconditioned stem cells comprise muscle stem cells and show increased differentiation into muscle fibers when compared to target stem cells that have not been exposed to LDR at a threshold aging time.
16 . The population of claim 15 , wherein the preconditioned muscle stem cells have higher expression of at least one marker selected from the group consisting of myogenin, MyH3, MyoD, TKS5 and TMEM8c compared to muscle stem cells that have not been exposed to LDR.
17 . A method of treating a muscle disease comprising administering a population of preconditioned muscle stem cells of claim 1 to a subject in need thereof.
18 . The method of claim 17 , wherein the subject is a human.