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Publication Number
US-10471102-B2
Publication Date
2019-11-12
Expiration Date
Abstract
Isolated extracellular matrix from marrow adherent stromal cells and their descendents, which stimulates the growth and survival of a number of different neural cell types, is provided, along with methods for preparation and uses.
Core Innovation
The invention provides isolated extracellular matrix (ECM) deposited by marrow adherent stromal cells (MASCs) and differentiation-restricted descendents (DRCs). The DRCs include DRCs produced by transfecting MASCs with a nucleic acid encoding Notch intracellular domain (NICD). The extracellular matrix is used in the context of treating neural degeneration or disorder in a subject by providing the extracellular matrix to the subject.
The extracellular matrix supports neural cell survival and growth, including neurons, astrocytes, and oligodendrocytes. It provides neurite outgrowth and enhanced neural marker expression, including MAP2, tau, GFAP, and CNPase. The described effects are reported as dose-dependent on the number of cells used to elaborate the ECM.
The disclosed extracellular matrix benefits are reported to occur beyond initial cell adhesion. The ECM improves survival in less supportive culture medium, and the document includes comparisons of ECM versus poly-D-lysine (PDL) and MASC-ECM versus DRC-ECM. The disclosure also outlines methods to produce ECM-coated substrates and to prepare DRCs/NICD-modified cells.
Claims Coverage
The independent claim covers a therapeutic method for neural degeneration or disorder in a subject that depends on producing an extracellular matrix (ECM) using NICD-encoding transfected marrow adherent stromal cells (MASCs), selecting for nucleic-acid-containing cells, and providing the resulting ECM to the subject. This independent claim contains three inventive features.
NICD-encoded marrow adherent stromal cell-derived extracellular matrix
The extracellular matrix is produced by a cell obtained by transfecting marrow adherent stromal cells with a nucleic acid comprising sequences encoding a Notch intracellular domain (NICD).
Selective-agent selection of nucleic-acid-containing NICD cells
The cell obtained in step (a) is cultured in the presence of a selective agent, thereby selecting cells comprising the nucleic acid.
Further culturing without the selective agent to obtain ECM for treatment
The selected cells are further cultured in the absence of the selective agent, and the extracellular matrix produced thereby is provided to the subject to treat neural degeneration or disorder.
Across the independent claim, the inventive concept centers on providing a treatment involving an extracellular matrix produced from NICD-transfected marrow adherent stromal cells, including selective-agent selection of nucleic-acid-containing cells followed by further culturing without the selective agent.
Stated Advantages
The extracellular matrix supports neural cell survival and growth.
The extracellular matrix provides neurite outgrowth.
The extracellular matrix provides enhanced neural marker expression (MAP2, tau, GFAP, CNPase).
The ECM benefits improve survival in less supportive culture medium.
The described effects are dose-dependent on the number of cells used to elaborate the ECM.
Documented Applications
Use of extracellular matrix to treat neural degeneration or disorder in a subject by providing the extracellular matrix to the subject.
Implantation at an injury site associated with neural degeneration or a neural disorder.
Use of matrix-bound growth factor function as part of the therapeutic method, including chemotactic/haptotactic stimulus actions for neurons and glia.
Treatment where the neural degeneration or disorder affects the central nervous system.
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