Intracoronary Transplantation of Mesenchymal Stem Cells with Overexpressed Integrin-Linked Kinase Improves Cardiac Function in Porcine Myocardial Infarction.

The effect of mesenchymal stem cell (MSCs)-based therapy on treating acute myocardial infarction (MI) is limited due to poor engraftment and limited regenerative potential. Here we engineered MSCs with integrin-linked kinase (ILK), a pleiotropic protein critically regulating cell survival, proliferation, differentiation, and angiogenesis. We firstly combined ferumoxytol with poly-L-lysine (PLL), and found this combination promisingly enabled MRI visualization of MSCs in vitro and in vivo with good safety. We provided visually direct evidence that intracoronary ILK-MSCs had substantially enhanced homing capacity to infarct myocardium in porcine following cardiac catheterization induced MI. Intracoronary transplantation of allogeneic ILK-MSCs, but not vector-MSCs, significantly enhanced global left ventricular ejection fraction (LVEF) by 7.8% compared with baseline, by 10.3% compared with vehicles, and inhibited myocardial remodeling compared with vehicles at 15-day follow-up. Compared with vector-MSCs, ILK-MSCs significantly improved regional LV contractile function, reduced scar size, fibrosis, cell apoptosis, and increased regional myocardial perfusion and cell proliferation. This preclinical study indicates that ILK-engineered MSCs might promote the clinical translation of MSC-based therapy in post-MI patients, and provides evidence that ferumoxytol labeling of cells combined with PLL is feasible in in vivo cell tracking.

Evaluation of apparent diffusion coefficient mappings in amnestic mild cognitive impairment using an image analysis software brain search.

BACKGROUND: The apparent diffusion coefficient (ADC) from diffusion-weighted imaging (DWI) can quantify alterations in water diffusivity resulting from microscopic structural changes from amnestic mild cognitive impairment (aMCI) and Alzheimer's disease (AD). PURPOSE: To investigate the ADC value for aMCI and AD using Brain Search (BS) software based on anatomical volumes of interest (AVOI). MATERIAL AND METHODS: In total, 174 aged people were screened, and 25 patients with AD, 26 patients with aMCI, and 18 normal controls (NCs) were recruited. DWI was performed at 1.5 T with a fluid-attenuated inversion recovery (FLAIR), and the independent ADC mapping was generated after imaging acquisition. Ninety regional parcellations were adopted in a Brain Search (BS) based on the automated anatomic labeling atlas. The gray scale intensities (water diffusivity) from the collected ADC mappings were analyzed with BS. The mean value of each anatomical brain region was compared among aMCI, AD, and NC. The statistically significant (P < 0.05) group differences are displayed in color. RESULTS: During the pathological process of AD, the changes of water diffusivity appeared first in the left hippocampus, then gradually progressed to the bilateral sides and eventually displayed right lateralization. The ADC values from aMCI were obviously elevated compared to the values from the NC group in the left limbic cortex. Between the AD and NC groups, the significantly different brain areas included the bilateral hippocampus, the Cingulum_Mid, the ParaHippocampal_R, and the Temporal and Frontal lobes. There was a negative correlation between the ADC values and the scores from MMSE, MoCA, the Digit test, Raven's IQ, and WAIS IQ. Additionally, the ADC values were positively correlated with the scores from CDR, ADL, and ADAS-Cog. CONCLUSION: The water diffusivity for aMCI and AD displays asymmetric anatomical lateralization. The water diffusivity alterations can be analyzed and visualized with our newly designed analytic imaging software, BS, which can be used as a good reference for examining and diagnosing aMCI and AD patients.