Superparamagnetic iron oxide nanoparticles regulate smooth muscle cell phenotype.

Ioannis Angelopoulos,Quentin A Pankhurst,Paul Southern,Richard M Day

doi:10.1002/jbm.a.35780

Ioannis Angelopoulos, Quentin A Pankhurst + Show 2 more

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https://doi.org/10.1002/jbm.a.35780

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Abstract

Superparamagnetic iron oxide nanoparticles (SPION) are used for an increasing range of biomedical applications, from imaging to mechanical actuation of cells and tissue. The aim of this study was to investigate the loading of smooth muscle cells (SMC) with SPION and to explore what effect this has on the phenotype of the cells. Adherent human SMC were loaded with ∼17 pg of unconjugated, negatively charged, 50 nm SPION. Clusters of the internalized SPION particles were held in discrete cytoplasmic vesicles. Internalized SPION did not cause any change in cell morphology, proliferation, metabolic activity, or staining pattern of actin and calponin, two of the muscle contractile proteins involved in force generation. However, internalized SPION inhibited the increased gene expression of actin and calponin normally observed when cells are incubated under differentiation conditions. The observed change in the control of gene expression of muscle contractile apparatus by SPION has not previously been described. This finding could offer novel approaches for regulating the phenotype of SMC and warrants further investigation. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2412–2419, 2016.

Highlights

Muscle insufficiency is a significant clinical challenge for a wide range of acquired and congenital clinical conditions
Loading human rectal smooth cells (HRSMC) with Superparamagnetic iron oxide nanoparticles (SPION) Following incubation of HRSMC in proliferation medium containing 250 lg/mL SPION for 24 h and subsequent washing stages to remove unbound particles, SPION clusters associated with the cells were clearly visible using light microscopy [Figure 1(a)]
Transmission electron microscopy (TEM) of the HRSMC incubated with SPION revealed the particles were held in vesicles inside the cytoplasm [Figure 1(b)]

Summary

Introduction

Muscle insufficiency is a significant clinical challenge for a wide range of acquired and congenital clinical conditions. Smooth muscle poses a specific set of challenges due to the lack of accessible sites suitable for harvesting autologous donor cells for regenerative medicine purposes. Smooth muscle cells (SMC) can switch between a differentiated “contractile” phenotype and a “proliferative” or “synthetic” phenotype.[1,2,3,4] The possibility of harnessing this phenotypic plasticity to form new tissues is an attractive strategy for the ex vivo bioengineering of various tissues, including arteries and sphincter muscle.[5,6] Shifting the proliferative SMC toward a contractile phenotype can be achieved via intra- or extracellular stimuli including soluble signalling factors, extracellular matrices, and mechanical stimulation. The resulting phenotypic state is characterized by the expression pattern of protein markers, proliferative capacity, and cell morphology.[7,8]

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