Department of Cellular and Molecular Biology, Islamic Azad University Tehran Medical Sciences, Tehran, Iran.
Physiology Research Center, Iran university of Medical Sciences, Tehran, Iran.
Drug Deliv Transl Res. 2018 Oct;8(5):1214-1225. doi: 10.1007/s13346-018-0567-8.
Migration of stem cells after transplantation reduces their therapeutic effects. In this study, we hypothesized that superparamagnetic iron oxide nanoparticles (SPION)-labeled mesenchymal stem cells (MSCs) in the presence of magnetic field may have a capability to increase regenerative ability after heart failure (HF). A rat model of ISO (isoproterenol)-HF was established to investigate the effects of SPION-labeled MSCs on tissue regeneration in the presence and absence of magnetic field. Hydrodynamic size, shape, and formation of chemical bonds between SPION and polyethylene glycol (PEG) were measured using dynamic light scattering (DLS), transmission electron microscopy (TEM), and Fourier-transform infrared spectroscopy (FTIR). The MRI was used to monitor SPION-labeled MSCs in vivo. Cell and tissue uptake of nanoparticles were determined by Prussian blue staining, atomic absorption spectroscopy (AAS), and inductively coupled plasma spectroscopy (ICP). Purity of the MSCs, heart function, myocardial fibrosis, and histologic damage were evaluated using flow-cytometry, echocardiography, Masson's trichrome, and H&E staining respectively. Various spectroscopic and microscopic analyses revealed that hydrodynamic size of SPION was 40 ± 2 and their shape was spherical. FTIR confirmed the presence of PEG on the surface of nanoparticles. The presence of magnetic field significantly increased cell homing. Highly purified MSCs population was detected by flow-cytometry. Using SPION-labeled MSCs in the presence of magnetic field markedly improved heart function and myocardial hypertrophy and reduced fibrosis (p < 0.05). Collectively, our results demonstrated that SPION-labeled MSCs in the presence of magnetic field might contribute to regeneration after HF.
细胞移植后的细胞迁移会降低其治疗效果。在这项研究中，我们假设在磁场存在的情况下，超顺磁性氧化铁纳米粒子（SPION）标记的间充质干细胞（MSCs）可能具有增加心力衰竭（HF）后再生能力的能力。建立了 ISO（异丙肾上腺素）-HF 的大鼠模型，以研究 SPION 标记的 MSC 在磁场存在和不存在的情况下对组织再生的影响。使用动态光散射（DLS）、透射电子显微镜（TEM）和傅里叶变换红外光谱（FTIR）测量 SPION 与聚乙二醇（PEG）之间的氢键形成、纳米颗粒的水动力尺寸、形状和形成。使用 MRI 监测体内 SPION 标记的 MSC。通过普鲁士蓝染色、原子吸收光谱（AAS）和电感耦合等离子体光谱（ICP）测定纳米颗粒的细胞和组织摄取。使用流式细胞术、超声心动图、Masson 三色和 H&E 染色分别评估 MSC 的纯度、心脏功能、心肌纤维化和组织学损伤。各种光谱和显微镜分析表明，SPION 的水动力尺寸为 40±2，其形状为球形。FTIR 证实了 PEG 存在于纳米颗粒的表面。磁场的存在显著增加了细胞归巢。通过流式细胞术检测到高度纯化的 MSC 群体。在磁场存在的情况下使用 SPION 标记的 MSC 显著改善了心脏功能和心肌肥大，并减少了纤维化（p<0.05）。综上所述，我们的结果表明，磁场存在下的 SPION 标记 MSC 可能有助于 HF 后的再生。
