Intramyocardial injection of bone marrow mononuclear cells (MNCs) with hyaluronan (HA) hydrogel is beneficial to the ischemic heart in a rat model of myocardial infarction (MI). However, the therapeutic efficacy and safety must be addressed in large animals before moving onto a clinical trial. Therefore, the effect of combined treatment on MI was investigated in pigs. Coronary artery ligation was performed in minipigs to induce MI followed by an intramyocardial injection of normal saline ( n = 7), HA ( n = 7), normal saline with 1 × 108 freshly isolated MNCs ( n = 8), or HA with 1 × 108 MNCs (HA-MNC; n = 7), with a sham-operated group serving as a control ( n = 7). The response of each experimental group was estimated by echocardiography, ventricular catheterization, and histological analysis. Although injection of HA or MNCs slightly elevated left ventricular ejection fraction, the combined HA-MNC injection showed a significant increase in left ventricular ejection fraction, contractility, infarct size, and neovascularization. Importantly, injection of MNCs with HA also promoted MNC retention and MNC differentiation into vascular lineage cells in pigs. Therefore, this study not only provides evidence but also raises the possibility of using a combined HA-MNC injection as a promising therapy for heart repair.
The therapeutic effects of PDA‐001 in mice with chronic heart failure (CHF) were tested. Three weeks after transaortic constriction surgery to induce CHF, the mice underwent direct injection of PDA‐001. Intramyocardial injection of PDA‐001 significantly improved left ventricular systolic and diastolic function and decreased cardiac fibrosis, demonstrating the cardiac therapeutic potential of PDA‐001.
Various nanoparticle (NP) properties such as shape and surface charge have been studied in an attempt to enhance the efficacy of NPs in biomedical applications. When trying to undermine the precise biodistribution of NPs within the target organs, the analytical method becomes the determining factor in measuring the precise quantity of distributed NPs. High performance liquid chromatography (HPLC) represents a more powerful tool in quantifying NP biodistribution compared to conventional analytical methods such as an in vivo imaging system (IVIS). This, in part, is due to better curve linearity offered by HPLC than IVIS. Furthermore, HPLC enables us to fully analyze each gram of NPs present in the organs without compromising the signals and the depth-related sensitivity as is the case in IVIS measurements. In addition, we found that changing physiological conditions improved large NP (200-500 nm) distribution in brain tissue. These results reveal the importance of selecting analytic tools and physiological environment when characterizing NP biodistribution for future nanoscale toxicology, therapeutics and diagnostics.
The unsurpassed properties in electrical conductivity, thermal conductivity, strength, and surface area-to-volume ratio allow for many potential applications of carbon nanomaterials in various fields. Recently, studies have characterized the potential of using carbon nanotubes (CNTs) as a biomaterial for biomedical applications and as a drug carrier via intravenous injection. However, most studies show that unmodified CNTs possess a high degree of toxicity and cause inflammation, mechanical obstruction from high organ retention, and other biocompatibility issues following in vivo delivery. In contrast, carbon nanocapsules (CNCs) have a lower aspect ratio compared with CNTs and have a higher dispersion rate. To investigate the possibility of using CNCs as an alternative to CNTs for drug delivery, heparin-conjugated CNCs (CNC-H) were studied in a mouse model of acute hindlimb thromboembolism. Our results showed that CNC-H not only displayed superior antithrombotic activity in vitro and in vivo but they also had the ability to extend the thrombus formation time far longer than an injection of heparin or CNCs alone. Therefore, the present study showed for the first time that functionalized CNCs can act as nanocarriers to deliver thrombolytic therapeutics.
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