Multipotential Expanded Mesenchymal Precursor Cell Progeny (MEMP) and Uses Thereof
AssigneeMesoblast, Inc.
InventorsStan Gronthos, Andrew Christopher William Zannettino
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Abstract
The invention relates to multipotential expanded mesenchymal precursor progeny (MEMP's), characterised by the early developmental markers STRO-1bri and ALP. The present invention also relates to methods for producing MEMP's and to uses of MEMP's for therapeutic applications.
Claims21
1-55. (canceled)
A composition comprising STRO-1bright mesenchymal progenitor cells (MPC) and a stimulation factor selected from the group consisting of 1α,25-dihydroxyvitamin D3 (1,25D), tumor necrosis factor α (TNF-α) and interleukin-1β (IL-1β).
The composition of claim 1 further comprising STRO-1dim tissue specific committed cells (TSCC).
The composition of claim 2, wherein the STRO-1dim TSCCs are bone precursor cells.
The composition of claim 3, wherein the bone precursor cells are STRO-1dim osteoprogenitor cells.
The composition of claim 1 further comprising dexamethasone.
An in vitro method of increasing the generation of multipotential expanded mesenchymal precursor cell progeny (MEMPs) that have the phenotype Stro-1bri ALP−, the method comprising culturing STRO-1bright mesenchymal progenitor cells (MPC) in the presence of one or more stimulatory factors selected from the group consisting of 1α,25-dihydroxyvitamin D3 (1,25D), tumor necrosis factor α (TNF-α), and interleukin-1β (IL-1β).
The method of claim 6, wherein the STRO-1bright MPC thereof are cultured in the presence of two or more stimulatory factors.
The method of claim 6, wherein the STRO-1bright MPC have been expanded ex vivo.
The method of claim 6, wherein the STRO-1bright MPC are an unexpanded population of isolated MPC.
The method of claim 6, wherein the stimulation results in an increase in MPC progeny that have the phenotype Stro-1bri, ALP− of more than 10% relative to non stimulated controls.
The method of claim 6, wherein the stimulation results in an increase in MPC progeny that have the phenotype Stro-1bri, ALP− of more than 50% relative to non stimulated controls.
The method of claim 6, wherein the STRO-1bright MPC are derived from any one or more tissues selected from the group consisting of bone marrow, dental pulp cells, adipose tissue and skin, or perhaps more broadly from adipose tissue, teeth, dental pulp, skin, liver, kidney, heart, retina, brain, hair follicles, intestine, lung, spleen, lymph node, thymus, pancreas, bone, ligament, bone marrow, tendon and skeletal muscle.
The composition of claim 2 further comprising dexamethasone.
The composition of claim 3 further comprising dexamethasone.
The composition of claim 4 further comprising dexamethasone.
The method of claim 7, wherein the STRO-1bright MPC have been expanded ex vivo.
The method of claim 7, wherein the STRO-1bright MPC are an unexpanded population of isolated MPC.
The method of claim 8, wherein the STRO-1bright MPC are an unexpanded population of isolated MPC.
The method of claim 7, wherein the stimulation results in an increase in MPC progeny that have the phenotype Stro-1bri, ALP− of more than 10% relative to non stimulated controls.
The method of claim 8, wherein the stimulation results in an increase in MPC progeny that have the phenotype Stro-1bri, ALP− of more than 10% relative to non stimulated controls.
Dependencies are inferred from the claim text.