Composition comprising cell and biocompatible polymer
Inventors
Miyoshi, Hayato • OKAMURA, Ai • TATE, Ciara C. • DAO, Monique A.
Assignees
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Publication Number
US-10406183-B2
Publication Date
2019-09-10
Expiration Date
Abstract
It is an object of the present invention to provide a cell-containing composition capable of suppressing the outflow of the cells after transplantation and improving the survival rate of the cells. The present invention provides a composition which comprises any of bone marrow stromal cell-derived neural precursor cells, bone marrow stromal cell-derived Schwann cells, or bone marrow stromal cell-derived skeletal muscle cells; and a biocompatible polymer.
Core Innovation
The invention relates to a method for treating injured central nervous system by administering a therapeutically effective amount of a composition that includes particles of a biocompatible polymer and particular cells derived from bone marrow. The method includes freeze-drying a hydrogel of the biocompatible polymer followed by milling to prepare particles. The administered composition comprises bone marrow stromal cell-derived neural precursor cells and/or bone marrow stromal cell-derived Schwann cells, together with the biocompatible polymer particles.
The neural precursor cells are obtained by introducing a nucleic acid comprising Notch sequences that encode a Notch intracellular domain, and culturing bone marrow stromal cells so that the bone marrow stromal cells differentiate into neural precursor cells. The resultant differentiated cells are offspring of bone marrow stromal cells into which the nucleic acid has been introduced. This Notch-sequence-based manipulation is part of the cell composition administered to the injured central nervous system.
The Schwann cells are obtained by collecting bone marrow stromal cells from bone marrow and culturing them in a standard essential culture medium supplemented with a serum, followed by further culturing after adding a reducing agent, adding retinoic acid, and adding forskolin and/or a differentiation, survival and growth factor which acts on nerves and glial cells. The method is directed to injured central nervous system including cerebral infarction caused by the necrosis of brain tissues due to ischemia, Parkinson's disease, or spinal cord injury caused by damaging the spinal cord by strong external force, with the polymer particles included as part of the administered composition.
Claims Coverage
The independent claim is clm-00001. It covers three inventive features: biocompatible-polymer particles prepared by freeze-drying and milling a hydrogel, Notch-manipulated bone marrow stromal cell-derived neural precursor cells, and bone marrow stromal cell-derived Schwann cells obtained by staged culture, for treating specified injured central nervous system.
Freeze-drying and milling biocompatible polymer hydrogel into particles for administration
A method comprising freeze-drying a hydrogel of a biocompatible polymer followed by milling to prepare particles, and administering to a patient a composition comprising the particles of the biocompatible polymer.
Notch intracellular domain nucleic-acid introduction to generate neural precursor cells from bone marrow stromal cells
Using bone marrow stromal cell-derived neural precursor cells obtained by introducing a nucleic acid comprising Notch sequences that encode a Notch intracellular domain, and culturing bone marrow stromal cells to differentiate into neural precursor cells, wherein the resultant differentiated cells are offspring of bone marrow stromal cells into which the nucleic acid has been introduced.
Staged culture of bone marrow stromal cells to obtain Schwann cells with nerve and glial factor stimulation
Using bone marrow stromal cell-derived Schwann cells obtained by collecting bone marrow stromal cells from bone marrow, culturing in a standard essential culture medium supplemented with a serum, adding a reducing agent, adding retinoic acid, and adding forskolin and/or a differentiation, survival and growth stimulating factor which acts on nerves and glial cells to obtain Schwann cells.
Treatment of injured central nervous system including ischemic cerebral infarction, Parkinson's disease, or strong-force spinal cord injury
Administering the composition to treat an injured central nervous system that is a cerebral infarction caused by necrosis of brain tissues due to ischemia, Parkinson's disease, or spinal cord injury caused by damaging the spinal cord by strong external force.
Across the independent claim, the core coverage is the combination of freeze-dried and milled biocompatible-polymer particles with Notch-intracellular-domain-manipulated bone marrow stromal cell-derived neural precursor cells and bone marrow stromal cell-derived Schwann cells obtained by staged culture, for treating specified forms of injured central nervous system.
Stated Advantages
Improving cell survival and suppressing cell outflow after transplantation (as stated in the provided summary of the document).
Improving in vivo survival and host neuron/myelin preservation in a stroke rat model (as stated in the provided summary of the document).
Documented Applications
Treating injured central nervous system in a stroke rat model using a transient middle cerebral artery occlusion (MCAo) for host neuron and myelin preservation (as stated in the provided summary of the document).
Comparing Schwann cell viability on CBE3 versus PDL-coated surfaces (as stated in the provided summary of the document).
In vitro hippocampal slice viability assessments using ultra low attachment culture plate and related assays (as stated in the provided summary of the document).
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