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Role of VEGF-A in angiogenesis promoted by umbilical cord-derived mesenchymal stromal/stem cells: in vitro study
- Source :
- Stem Cell Research & Therapy
- Publication Year :
- 2016
- Publisher :
- Springer Science and Business Media LLC, 2016.
-
Abstract
- Background Mesenchymal stromal/stem cells derived from human umbilical cord (UC-MSCs) uniquely combine properties of embryonic and postnatal MSCs and may be the most acceptable, safe, and effective source for allogeneic cell therapy e.g. for therapeutic angiogenesis. In this report we describe pro-angiogenic properties of UC-MSCs as manifested in vitro. Methods UC-MSCs were isolated from human Wharton’s jelly by enzymatic digestion. Presence of soluble forms of VEGF-A in UC-MSC-conditioned media was measured by ELISA. Effects of the conditioned media on human umbilical vein-derived endothelial EA.hy926 cells proliferation were measured by MTT-assay; changes in cell motility and directed migration were assessed by scratch wound healing and transwell chamber migration assays. Angiogenesis was modeled in vitro as tube formation on basement membrane matrix. Progressive differentiation of MSCs to endothelioid progeny was assessed by CD31 immunostaining. Results Although no detectable quantities of soluble VEGF-A were produced by UC-MSCs, the culture medium, conditioned by the UC-MSCs, effectively stimulated proliferation, motility, and directed migration of EA.hy926 cells. In 2D culture, UC-MSCs were able to acquire CD31+ endothelial cell-like phenotype when stimulated by EA.hy926-conditioned media supplemented with VEGF-A165. UC-MSCs were capable of forming unstable 2D tubular networks either by themselves or in combinations with EA.hy926 cells. Active spontaneous sprouting from cell clusters, resulting from disassembling of such networks, was observed only in the mixed cultures, not in pure UC-MSC cultures. In 3D mode of sprouting experimentation, structural support of newly formed capillary-like structures was provided by UC-MSCs that acquired the CD31+ phenotype in the absence of exogenous VEGF-A. Conclusion These data suggest that a VEGF-A-independent paracrine mechanism and at least partially VEGF-A-independent differentiation mechanism are involved in the pro-angiogenic activity of UC-MSCs.
- Subjects :
- Vascular Endothelial Growth Factor A
0301 basic medicine
Vascular endothelial growth factor-A
Stromal cell
Angiogenesis
Endothelial cells
Cellular differentiation
Mesenchymal stromal cells
Neovascularization, Physiologic
Medicine (miscellaneous)
Biochemistry, Genetics and Molecular Biology (miscellaneous)
Cell Line
Umbilical Cord
In vitro techniques
03 medical and health sciences
Cell Movement
Cell migration assays
Wharton's jelly
Humans
Cell Proliferation
CD31 antigen
Chemistry
Research
Mesenchymal stem cell
Cell Differentiation
Mesenchymal Stem Cells
Extracellular matrix
Cell Biology
Cell biology
Endothelial stem cell
Multipotent
030104 developmental biology
Culture Media, Conditioned
Angiogenesis inducing agents
Immunology
Molecular Medicine
Wharton jelly
Stem cell
Adult stem cell
Subjects
Details
- ISSN :
- 17576512
- Volume :
- 7
- Database :
- OpenAIRE
- Journal :
- Stem Cell Research & Therapy
- Accession number :
- edsair.doi.dedup.....f6c0b51d320da050cff1904a67b3215e