Targeted delivery of vascular endothelial growth factor improves stem cell therapy in a rat myocardial infarction model

Abstract

Rebuilding of infarcted myocardium by mesenchymal stem cells (MSCs) has not been successful because of poor cell survival due in part to insufficient blood supply after myocardial infarction (MI). We hypothesize that targeted delivery of vascular endothelial growth factor (VEGF) to MI can help regenerate vasculature in support of MSC therapy in a rat model of MI. VEGF-encapsulated immunoliposomes targeting overexpressed P-selectin in MI tissue were infused by tail vein immediately after MI. One week later, MSCs were injected intramyocardially. The cardiac function loss was moderated slightly by targeted delivery of VEGF or MSC treatment, while targeted VEGF + MSC combination treatment showed highest attenuation in cardiac function loss. The combination treatment also markedly increased blood vessel density (80%) and decreased the collagen content in post-MI tissue (33%). Engraftment of MSCs in the combination treatment group was significantly increased and the engrafted cells contributed to the restoration of blood vessels.

Pharmaceutical liposomal drug delivery: a review of new delivery systems and a look at the regulatory landscape

“…In the cell therapy space, liposomes were shown to be efficient for the targeted delivery of growth factors such as vascular endothelial growth factor (VEGF (Tang et al, 2014)), VEGF aptamers (Willis et al, 1998) and endothelial growth factor (EGF (Alemdaroglu et al, 2008)) as well as small interfering RNA (siRNA (Wang et al, 2013)). Tang et al (2014) recently developed VEGF-encapsulated immunoliposomes targeting myocardial infarction (MI).…”

“…Tang et al (2014) recently developed VEGF-encapsulated immunoliposomes targeting myocardial infarction (MI). By injecting the VEGF-immunoliposomes together with mesenchymal stem cells (MSCs) into a rat immediately following MI, the authors observed a remarkably high attenuation in cardiac function loss, together with an 80% increase in blood vessel density.…”

Insight on stem cell preconditioning and instructive biomaterials to enhance cell adhesion, retention, and engraftment for tissue repair

“…Priming MSCs with these trophic factors has been reported to enhance cell survival and retention. Recently, Tang et al [133] reported that exogenously expressed VEGF promoted myocardial repair at least in part through SDF-1a/CXCR4-mediated migration of CSCs. Similarly, CSCs treated with SDF-1a demonstrated better engraftment and retention at the infarcted area as well as higher levels of proliferation.…”

Targeted multidrug delivery system to overcome chemoresistance in breast cancer

“…31 Briefly, all four lipid components were dissolved in chloroform (Sigma-Aldrich), which was then removed by nitrogen gas purging at room temperature, followed by overnight evaporation in a Labconco Freezone 1 freeze-dryer (Kansas City, MO, USA). The resulting lipid film was hydrated with a 250 mM ammonium sulfate (SigmaAldrich) solution by gentle mixing, resulting in spontaneously organized multilamellar vesicles (MLVs).…”