Methods and compositions for expansion of cell population
AssigneesStowers Institute for Medical Research, The University of Chicago
InventorsZhenrui Li, Pengxu Qian, Linheng Li, Chuan He
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Abstract
The present invention relates to methods for expanding a stem cell population, as well as other cell populations. More particularly, the invention relates, inter alia, to methods and compositions for expanding a stem cell and/or other cell population, particularly a hematopoietic stem cell population.
Claims110
A method for expanding a population of stem cells obtained from a tissue selected from the group consisting of peripheral blood, cord blood and bone marrow, the method comprising modulating a N6-Methyladenosine (m6A) mRNA modification pathway in the population of stem cells, to expand the number of stem cells.
A method for ex vivo expansion of a substantially undifferentiated stem cell population comprising modulating a N6-Methyladenosine (m6A) mRNA modification pathway in the undifferentiated stem cell population to expand the number of undifferentiated stem cells without significant differentiation of the stem cell population.
A method for ex vivo expansion of an hematopoietic stem cell (HSC) population obtained from a tissue selected from the group consisting of peripheral blood, cord blood, and bone marrow, the method comprising modulating a N6-Methyladenosine (m6A) mRNA modification pathway in the HSC population to expand the HSC population to a sufficient quantity while maintaining a multilineage differentiation potential in the HSC population, which is sufficient for subsequent transplantation into a subject in need thereof.
A method for ex vivo expansion of hematopoietic stem cells (HSCs) by at least 2-fold, the expanded HSCs being competent to reconstitute an HSC lineage upon transplantation into a mammal in need thereof, the method comprising introducing a mutation into the stem cells that results in deletion, replacement or reduced expression of a gene expressing a m6A mRNA modification reader and culturing the population of HSCs in a suitable culture medium.
A kit for expanding an hematopoietic stem cell population (HSC) population for subsequent transplantation into a subject in need thereof, the kit comprising a system for introducing a mutation into the HSC population that results in deletion, replacement or reduced expression of a gene expressing a m6A mRNA modification reader, and instructions for use thereof.
A kit for expanding an hematopoietic stem cell population (HSC) population for subsequent transplantation into a subject in need thereof, the kit comprising an inhibitor of a m6A mRNA modification reader, and instructions for use thereof.
A method for administering an hematopoietic stem cell (HSC) to a subject in need thereof, the method comprising:
- (a) introducing, into a sample containing an HSC population, a mutation that results in deletion, replacement or reduced expression of a gene expressing a m6A mRNA modification reader,
- (b) culturing the sample in a suitable culture media for a period of time sufficient to expand the number of HSCs in the sample to a number sufficient to transplant into the subject;
- and
- (c) administering the HSCs to the subject.
A method for administering an hematopoietic stem cell (HSC) to a subject in need thereof, the method comprising:
- (a) culturing, in a suitable culture media, a sample containing an HSC population in the presence of an inhibitor of a m6A mRNA modification reader, for a period of time sufficient to expand the number of HSCs in the sample to a number sufficient to transplant into the subject;
- (b) removing from the culture the inhibitor of the m6A mRNA modification reader;
- and
- (c) administering the HSCs to the subject.
A method for reconstituting bone marrow in a subject in need thereof, comprising:
- (a) introducing, into a sample containing an HSC population, a mutation that results in deletion, replacement or reduced expression of a gene expressing a m6A mRNA modification reader,
- (b) culturing the sample in a suitable culture media for a period of time sufficient to expand the number of HSCs in the sample to a number sufficient to transplant into the subject;
- (c) administering the HSCs to the subject.
A method for reconstituting bone marrow in a subject in need thereof, comprising:
- (a) culturing, in a suitable culture media, a sample containing an HSC population in the presence of an inhibitor of a m6A mRNA modification reader, for a period of time sufficient to expand the number of HSCs in the sample to a number sufficient to transplant into the subject;
- (b) removing from the culture the inhibitor of the m6A mRNA modification reader;
- and
- (c) administering the HSCs to the subject.
A method for expanding a population of hematopoietic cells (HSCs) comprising culturing the population of HSCs under conditions sufficient to result in an expansion of the HSC population by at least 2-fold, wherein the expanded population of HSCs is suitable for transplantation into a mammal in need thereof.
A method for expanding a population of hematopoietic stem cells (HSCs) comprising:
- (a) obtaining from a mammal a tissue sample comprising an HSC population;
- (b) expanding, in vitro, the HSC population from the sample, wherein:
- (i) the HSC population expands by at least 2-fold;
- and
- (ii) the expanded HSC population has at least a 5-fold increase in total colony-forming units.
A method for reconstituting a hematopoietic stem cell lineage in a subject in need thereof, the method comprising:
- (a) obtaining from a mammal a tissue sample comprising an HSC population;
- (b) expanding, in vitro, the HSC population from the sample, wherein:
- (i) the HSC population expands by at least 2-fold;
- and
- (ii) the expanded HSC population has at least a 5-fold increase in total colony-forming units;
- and
- (c) transplanting the expanded HSC population into a subject in need thereof.
A method for expanding a hematopoietic stem cell population in a mammal in need of such expansion comprising administering to the mammal a therapeutically effective amount of a modulator of a N6-Methyladenosine (m6A) mRNA modification pathway for a period of time sufficient to expand the HSC population by at least 2-fold with HSCs that possess the ability to reconstitute a hematopoietic lineage in the mammal.
-407. (canceled)
Dependencies are inferred from the claim text.