Therapeutic apoptotic cell preparations, method for producing same and uses thereof
The present application provides pharmaceutical compositions comprising a population of mononuclear-enriched cells in an early-apoptotic state, methods for the production of said compositions and uses thereof in the treatment of diseases characterized by pathological immune responses. The pharmaceutical compositions may be used in treatment of conditions such as, but not limited to, graft versus host disease (GVHD) and autoimmune diseases including but not limited to inflammatory bowel disease, gout and arthritis.
1. A stable, high yield early-apoptotic mononuclear-enriched cell population comprising a yield of at least 30% early apoptotic mononuclear-enriched cells, wherein said early-apoptotic cell population is stable for more than 24 hours, wherein production of said cell population comprises the following steps:
(a) freezing a mononuclear-enriched cell population in a freezing medium comprising an anticoagulant;
(b) thawing said mononuclear-enriched cell population; and
(c) inducing apoptosis in said thawed mononuclear-enriched cell population, said inducing comprising incubating said population in a medium comprising methylprednisolone and an anticoagulant.
2. The cell population of claim 1 , wherein said mononuclear enriched cells comprise at least one cell type selected from the group consisting of lymphocytes, monocytes and natural killer cells.
3. The cell population of claim 1 , wherein said mononuclear enriched cells are collected by leukapheresis.
4. The cell population of claim 1 , wherein said mononuclear enriched cells are obtained from a subject in need of receiving administration of a stable early apoptotic cell population.
5. The cell population of claim 1 , wherein said mononuclear enriched cells are obtained from a subject allogeneic with a subject in need of receiving administration of a stable early apoptotic cell population.
6. A pharmaceutical composition, comprising a stable early-apoptotic mononuclear-enriched cell population comprising at least 30% early apoptotic mononuclear-enriched cells wherein said early-apoptotic cell population is stable for more than 24 hours, wherein production of said cell population comprises the following steps:
(a) freezing a mononuclear-enriched cell population in a freezing medium comprising an anticoagulant;
(b) thawing said mononuclear-enriched cell population; and
(c) inducing apoptosis in said thawed mononuclear-enriched cell population, said inducing comprising incubating said population in a medium comprising methylprednisolone and an anticoagulant.
7. The pharmaceutical composition of claim 6 , wherein said composition further comprises an anti-coagulant.
8. A method for producing a pharmaceutical composition comprising a stable early-apoptotic mononuclear-enriched cell population comprising at least 30% early apoptotic mononuclear-enriched cells wherein said early-apoptotic cell population is stable for more than 24 hours, said method comprising a step of freezing a population of mononuclear-enriched cells in a freezing medium comprising an anticoagulant, and a step of inducing apoptosis of said mononuclear-enriched population in a medium comprising methylprednisolone and an anticoagulant, or a combination thereof.
9. The method of claim 8 , wherein said mononuclear enriched cells are collected by leukapheresis.
10. The method of claim 8 , wherein said mononuclear enriched cells are obtained from a subject in need of receiving administration of a stable early apoptotic cell population.
11. The method of claim 8 , wherein said mononuclear enriched cells are obtained from a subject allogeneic with a subject in need of receiving administration of a stable early apoptotic cell population.