Cell-based regenerative therapies are significantly improved by engineering allografts to express factors that increase vascularization and engraftment, such as placental growth factor (PlGF) and matrix metalloproteinase 9 (MMP9). Moreover, the seeding of therapeutic cells onto a suitable scaffold is of utmost importance for tissue regeneration. On these premises, we sought to assess the reparative potential of induced pluripotent stem (iPS) cells bioengineered to secrete PlGF or MMP9 and delivered to infarcted myocardium upon a poly(ethylene glycol)-fibrinogen scaffold. When assessing optimal stiffness of the PEG-fibrinogen (PF) scaffold, we found that the appearance of contracting cells after cardiogenic induction was accelerated on the support designed with an intermediate stiffness. Revascularization and hemodynamic parameters of infarcted mouse heart were significantly improved by injection into the infarct of this optimized PF scaffold seeded with both MiPS (iPS cells engineered to secrete MMP9) and PiPS (iPS cells engineered to secrete PlGF) cells as compared with nonengineered cells or PF alone. Importantly, allograft-derived cells and host myocardium were functionally integrated. Therefore, survival and integration of allografts in the ischemic heart can be significantly improved with the use of therapeutic cells bioengineered to secrete MMP9 and PlGF and encapsulated within an injectable PF hydrogel having an optimized stiffness.

Bearzi, C., Gargioli, C., Baci, D., Fortunato, O., Shapira Schweitzer, K., Kossover, O., et al. (2014). PlGFMMP9-engineered iPS cells supported on a PEGfibrinogen hydrogel scaffold possess an enhanced capacity to repair damaged myocardium. CELL DEATH & DISEASE, 5(2), e1053 [10.1038/cddis.2014.12].

PlGFMMP9-engineered iPS cells supported on a PEGfibrinogen hydrogel scaffold possess an enhanced capacity to repair damaged myocardium

GARGIOLI, CESARE;
2014-02-13

Abstract

Cell-based regenerative therapies are significantly improved by engineering allografts to express factors that increase vascularization and engraftment, such as placental growth factor (PlGF) and matrix metalloproteinase 9 (MMP9). Moreover, the seeding of therapeutic cells onto a suitable scaffold is of utmost importance for tissue regeneration. On these premises, we sought to assess the reparative potential of induced pluripotent stem (iPS) cells bioengineered to secrete PlGF or MMP9 and delivered to infarcted myocardium upon a poly(ethylene glycol)-fibrinogen scaffold. When assessing optimal stiffness of the PEG-fibrinogen (PF) scaffold, we found that the appearance of contracting cells after cardiogenic induction was accelerated on the support designed with an intermediate stiffness. Revascularization and hemodynamic parameters of infarcted mouse heart were significantly improved by injection into the infarct of this optimized PF scaffold seeded with both MiPS (iPS cells engineered to secrete MMP9) and PiPS (iPS cells engineered to secrete PlGF) cells as compared with nonengineered cells or PF alone. Importantly, allograft-derived cells and host myocardium were functionally integrated. Therefore, survival and integration of allografts in the ischemic heart can be significantly improved with the use of therapeutic cells bioengineered to secrete MMP9 and PlGF and encapsulated within an injectable PF hydrogel having an optimized stiffness.
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore BIO/06
English
Animals; Cell Survival; Cells, Cultured; Disease Models, Animal; Female; Fibrinogen; Hemodynamics; Human Umbilical Vein Endothelial Cells; Humans; Induced Pluripotent Stem Cells; Male; Matrix Metalloproteinase 9; Mice; Mice, Inbred NOD; Mice, SCID; Myocardial Contraction; Myocardial Infarction; Myocardium; Myocytes, Cardiac; Neovascularization, Physiologic; Polyethylene Glycols; Pregnancy Proteins; Recovery of Function; Time Factors; Tissue Engineering; Transduction, Genetic; Transfection; Genetic Engineering; Regeneration; Tissue Scaffolds
Bearzi, C., Gargioli, C., Baci, D., Fortunato, O., Shapira Schweitzer, K., Kossover, O., et al. (2014). PlGFMMP9-engineered iPS cells supported on a PEGfibrinogen hydrogel scaffold possess an enhanced capacity to repair damaged myocardium. CELL DEATH & DISEASE, 5(2), e1053 [10.1038/cddis.2014.12].
Bearzi, C; Gargioli, C; Baci, D; Fortunato, O; Shapira Schweitzer, K; Kossover, O; Latronico, M; Seliktar, D; Condorelli, G; Rizzi, R
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2108/136656
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