Mesenchymal stem cells and bone-forming cells
Inventors
Badoer, Cindy • Bastianelli, Enrico • Pesesse, Xavier
Assignees
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Publication Number
US-9371515-B2
Publication Date
2016-06-21
Expiration Date
Abstract
The invention relates to a new type of mesenchymal stem cells (MSC) which co-express at least one mesenchymal marker, preferably at least CD105 and CD34. Also provided are bone-forming cells having an analogous phenotype. The invention also provides the cells and cell populations, as well as further products comprising such and uses thereof in bone therapy.
Core Innovation
The invention concerns an MSC subpopulation and analogous bone-forming cells defined by co-expression of mesenchymal markers with CD34. The mesenchymal markers are preferably CD105 and/or CD90 and/or CD73, thereby identifying CD34-positive bone-forming osteogenic cells. The described CD34-positive, ALP-high osteogenic cells show enhanced bone matrix/mineralization together with pro-angiogenic behavior.
The pro-angiogenic behavior is associated with vWF/VEGF, including behavior measured by Matrigel tube formation assay. The invention provides a disclosed and exemplified approach for in vitro expanding and enriching these cells by exposing them to haematopoietic and/or angiogenic growth factors. The exposure is performed using haematopoietic factors and angiogenic factors that support increased enrichment and/or proliferation while maintaining the marker phenotype.
The disclosure further includes osteogenic differentiation, including differentiation of the CD34+ MSC into osteogenic lineages. Example results described in the document report increased CD34+/CD105+ fractions and increased expansion yield. The document also reports improved ALP and mineralization scores when using combined haematopoietic factors (e.g., GM-CSF and IFN-γ) together with angiogenic factors (e.g., PDGF, FGF-1, and FGF-3).
Claims Coverage
The partial content provides two independent claims, each directed to an in vitro expanding method that exposes specific cell populations to specified growth factor combinations. Across the independent claims, the inventive features center on exposing cells to FGF-2 and at least one of plasma or serum, together with selected additional factors and a specified bone-forming cell type.
In vitro expanding of MSCs by exposing with FGF-2 plus plasma or serum and selected factors
A method for in vitro expanding of Mesenchymal Stem Cells (MSCs), comprising exposing said MSCs to fibroblast growth factor 2 (FGF-2); at least one of plasma or serum; and one or more factors selected from granulocyte monocytes CSF (GM-CSF), Interferon-γ (IFN-γ), platelet-derived growth factor (PDGF) and FGF-3.
In vitro expanding of osteoblasts/osteoblastic cells by exposing with FGF-2 plus plasma or serum and selected factors
A method for in vitro expanding of bone-forming cells comprising exposing said bone-forming cells to FGF-2; at least one of plasma or serum; and one or more factors selected from GM-CSF, IFN-γ, FGF-1 and FGF-3, wherein said bone-forming cells are osteoblasts or osteoblastic cells.
Overall, the independent claims cover exposing MSCs or bone-forming cells (osteoblasts/osteoblastic cells) to FGF-2 together with at least one of plasma or serum, and adding selected haematopoietic and/or growth factors (GM-CSF, IFN-γ, PDGF, FGF-1, and FGF-3) to drive in vitro expansion.
Stated Advantages
Enhanced bone matrix/mineralization in the CD34-positive, ALP-high osteogenic cells.
Pro-angiogenic behavior associated with vWF/VEGF, including Matrigel tube formation assay behavior.
Increased enrichment/proliferation of the target cell population while maintaining the marker phenotype.
Improved ALP and mineralization scores.
Increased CD34+/CD105+ fractions.
Increased expansion yield.
Documented Applications
Bone reconstruction via expanded/enriched CD34-positive osteogenic cell populations with pro-angiogenic behavior.
Use as a pharmaceutical composition.
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