Integration of induced pluripotent stem cell-derived endothelial cells with polycaprolactone/gelatin-based electrospun scaffolds for enhanced therapeutic angiogenesis.

Autor: Tan RP; The Heart Research Institute, Sydney, NSW, 2042, Australia. richard.tan@hri.org.au.; Sydney Medical School, University of Sydney, Sydney, NSW, 2006, Australia. richard.tan@hri.org.au., Chan AHP; The Heart Research Institute, Sydney, NSW, 2042, Australia.; Sydney Medical School, University of Sydney, Sydney, NSW, 2006, Australia., Lennartsson K; The Heart Research Institute, Sydney, NSW, 2042, Australia., Miravet MM; The Heart Research Institute, Sydney, NSW, 2042, Australia., Lee BSL; The Heart Research Institute, Sydney, NSW, 2042, Australia.; Sydney Medical School, University of Sydney, Sydney, NSW, 2006, Australia., Rnjak-Kovacina J; Graduate School of Biomedical Engineering, University of New South Wales, Sydney, NSW, 2052, Australia., Clayton ZE; The Heart Research Institute, Sydney, NSW, 2042, Australia., Cooke JP; Department of Cardiovascular Sciences, Houston Methodist Research Institute, Houston, TX, 77030, USA., Ng MKC; The Heart Research Institute, Sydney, NSW, 2042, Australia.; Royal Prince Alfred Hospital, Sydney, NSW, 2042, Australia., Patel S; The Heart Research Institute, Sydney, NSW, 2042, Australia.; Royal Prince Alfred Hospital, Sydney, NSW, 2042, Australia., Wise SG; The Heart Research Institute, Sydney, NSW, 2042, Australia.; Sydney Medical School, University of Sydney, Sydney, NSW, 2006, Australia.
Jazyk: angličtina
Zdroj: Stem cell research & therapy [Stem Cell Res Ther] 2018 Mar 21; Vol. 9 (1), pp. 70. Date of Electronic Publication: 2018 Mar 21.
DOI: 10.1186/s13287-018-0824-2
Abstrakt: Background: Induced pluripotent stem-cell derived endothelial cells (iPSC-ECs) can be generated from any somatic cell and their iPSC sources possess unlimited self-renewal. Previous demonstration of their proangiogenic activity makes them a promising cell type for treatment of ischemic injury. As with many other stem cell approaches, the low rate of in-vivo survival has been a major limitation to the efficacy of iPSC-ECs to date. In this study, we aimed to increase the in-vivo lifetime of iPSC-ECs by culturing them on electrospun polycaprolactone (PCL)/gelatin scaffolds, before quantifying the subsequent impact on their proangiogenic function.
Methods: iPSC-ECs were isolated and stably transfected with a luciferase reporter to facilitate quantification of cell numbers and non-invasive imaging in-vivo PCL/gelatin scaffolds were engineered using electrospinning to obtain woven meshes of nanofibers. iPSC-ECs were cultured on scaffolds for 7 days. Subsequently, cell growth and function were assessed in vitro followed by implantation in a mouseback subcutaneous model for 7 days.
Results: Using a matrix of conditions, we found that scaffold blends with ratios of PCL:gelatin of 70:30 (PG73) spun at high flow rates supported the greatest levels of iPSC-EC growth, retention of phenotype, and function in vitro. Implanting iPSC-ECs seeded on PG73 scaffolds in vivo improved their survival up to 3 days, compared to cells directly injected into control wounds, which were no longer observable within 1 h. Enhanced engraftment improved blood perfusion, observed through non-invasive laser Doppler imaging. Immunohistochemistry revealed a corresponding increase in host angiogenic mechanisms characterized by the enhanced recruitment of macrophages and the elevated expression of proangiogenic cytokines vascular endothelial growth factor and placental growth factor.
Conclusions: Knowledge of these mechanisms combined with a deeper understanding of the scaffold parameters influencing this function provides the groundwork for optimizing future iPSC-EC therapies utilizing engraftment platforms. The development of combined scaffold and iPSC-EC therapies could ultimately improve therapeutic angiogenesis and the treatment of ischemic injury.
Databáze: MEDLINE
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