Methods and compositions for stimulation of cell proliferation and provision of biologically active mixtures of FGF2 isoforms
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Publication Number
US-10363285-B2
Publication Date
2019-07-30
Expiration Date
Abstract
Disclosed herein are methods and compositions for providing mixtures of FGF2 isoforms that are biologically active. The biological activities include, but are not limited to, stimulation of proliferation of neural precursor cells, stimulation of proliferation of endothelial cells, stimulation of development of neural precursor cells, and stimulation of development of astrocytes.
Core Innovation
The invention provides a mixture of cytoplasmic fibroblast growth factor-2 (FGF-2) isoforms to a cell, tissue or subject. The mixture is present as an isoform mixture released from mesenchymal cells, including fibroblasts, MSCs, and DNTT-MSCs, and the cytoplasmic FGF2 isoforms are released upon cell damage or lysis.
Descendants of mesenchymal stem cells (MSCs) are transiently transfected with a vector comprising sequences encoding a Notch intracellular domain (NICD). Preparations obtained from these descendants include a soluble cell-free extract and/or an insoluble cell residue, and these preparations comprise multiple cytoplasmic FGF2 isoforms, including isoforms having molecular weights of 18, 22, 22.5, and 24 kD.
The released mixture of FGF2 isoforms is used to induce neural precursor cell proliferation and endothelial cell proliferation, supporting neural development. The document further states astrocyte lineage development via live plus dead mesenchymal cell combinations and therapeutic contexts including ischemic injury, including stroke, and necrotic tissue, such as infarction and traumatic injury.
Claims Coverage
The independent claims cover a method of providing a mixture of cytoplasmic FGF-2 isoforms to a cell, tissue or subject and a preparation obtained from mesenchymal cells for use in that method. Across these independent claims, the inventive features include the NICD-transfected MSC descendant source, the provision of cytoplasmic FGF-2 isoform mixtures, and the preparation selection between soluble cell-free extract and insoluble cell residue, with an isoform molecular-weight specification in the preparation claim.
Providing cytoplasmic FGF-2 isoform mixture from NICD-transfected MSC descendants
A method comprising contacting a cell, tissue or subject with a preparation obtained from descendants of mesenchymal stem cells (MSCs) that have been transiently transfected with a vector comprising sequences encoding a Notch intracellular domain (NICD), wherein the preparation provides a mixture of cytoplasmic FGF-2 isoforms to the cell, tissue or subject.
Soluble cell-free extract and/or insoluble cell residue preparation selection
The method further specifies that the preparation is selected from one or both of a soluble cell-free extract and an insoluble cell residue.
Use preparation defined by cytoplasmic FGF-2 isoform molecular weights
A preparation, obtained from mesenchymal cells, for use in a method of providing a mixture of cytoplasmic FGF-2 isoforms, wherein the isoforms are selected from those having molecular weights of 18, 22, 22.5 and 24 kD.
Preparation selection and NICD-transfected MSC descendant source
The preparation for use is selected from one or both of a soluble cell-free extract and an insoluble cell residue, and wherein the mesenchymal cells are descendants of MSCs that have been transiently transfected with a vector comprising sequences encoding a Notch intracellular domain (NICD).
Overall, the claim set covers providing cytoplasmic FGF-2 isoform mixtures using preparations from NICD-transiently-transfected MSC descendants, with preparation selection between soluble cell-free extract and/or insoluble cell residue. The preparation claim additionally limits the mixture to isoforms with molecular weights of 18, 22, 22.5 and 24 kD.
Stated Advantages
Greater biological activity than recombinant FGF2.
Documented Applications
Inducing neural precursor cell proliferation.
Inducing endothelial cell proliferation.
Supporting neural development, including astrocyte lineage development via live plus dead mesenchymal cell combinations.
Therapeutic contexts including ischemic injury, including stroke.
Therapeutic contexts including necrotic tissue, including infarction and traumatic injury.
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