Biomedical use of radiation is utilized in effective diagnostic and treatment tools, yet can introduce risks to healthy tissues. High energy photons used for diagnostic purposes have high penetration ...depth and can discriminate multiple tissues based on attenuation properties of different materials. Likewise, the ability to deposit energy at various targets within tumors make the use of photons effective treatment for cancer. Radiation focused on a tumor will deposit energy when it interacts with a biological structure (e.g. DNA), which will result in cell kill should repair capacity of the tissue be overwhelmed. Likewise, damage to normal, non-cancerous tissues is a consequence of radiation that can lead to acute or late, chronic toxicity profiles. Adipose derived stem cells (ADSCs) are mesenchymal stem cells that have been proven to have similar characteristics to bone marrow derived stem cells, except that they are much easier to obtain. Within the body, ADSCs act as immunomodulators and assist with the maintenance and repair of tissues. They have been shown to have excellent differentiation capability, making them an extremely viable option for stem cell therapies and regenerative medicine applications. Due to the tissue ADSCs are derived from, they are highly likely to be affected by radiation therapy, especially when treating tumors localized to structures with relatively high ADSC content (eg., breast cancer). For this reason, the purpose behind this research is to better understand how ADSCs are affected by doses of radiation comparable to a single fraction of radiation therapy. We also measured the response of ADSCs to exposure at different dose rates to determine if there is a significant difference in the response of ADSCs to radiation therapy relevant doses of ionizing radiation. Our findings indicate that ADSCs exposed to Cesium (Cs 137)-gamma rays at a moderate dose of 2Gy and either a low dose rate (1.40Gy/min) or a high dose rate (7.31Gy/min) slow proliferation rate, and with cell cycle arrest in some populations. These responses ADSCs were not as marked as previously measured in other stem cell types. In addition, our results indicate that differences in dose rate in the Gy/min range typically utilized in small animal or cell irradiation platforms have a minimal effect on the function of ADSCs. The potential ADSCs have in the space of regenerative medicine makes them an ideal candidate for study with ionizing radiation, as they are one of the main cell types to promote tissue healing.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Restenosis by neointimal hyperplasia is still an ongoing concern in endovascular surgery. Slowing vascular smooth muscle cell (VSMC) proliferation by reversing the phenotype change, would allow ...vessel healing and re-endotheliazation. To accomplish this, we have developed heparin-coated magnetic nanoparticles for targeted drug therapy of neointimal hyperplasia. Iron oxide nanoparticles were modified with a poly (ethylene oxide) based coating and then further functionalized with heparin. In vitro experiments were conducted to observe changes in phenotype, metabolic activity, and viability of three relevant cell lines including VSMC, endothelial cells and fibroblasts. Inhibition of proliferation of VSMCs was observed with doses as low as 1 μg/mL Fe of heparin loaded nanoparticle where endothelial cells showed an increase in proliferation in response to treatment. Fibroblasts showed relatively low response. Results suggest proliferation suppression of VSMCs due to phenotype coupled with the increase in endothelial cell proliferation at low doses of heparin coated nanoparticles.
Cartoon representation of multifunctional iron oxide nanoparticle with catechol binding groups attached to a polyacrylic acid (PAA) backbone. This backbone was modified with heterobifunctional polyethylene oxide (PEO) stabilizers with heparin end groups. The resulting interactions with different cell lines is shown on the right-hand side of the graphic. Display omitted
The use of stents in the treatment of atherosclerosis leads to a potential risk of restenosis, caused by neointimal hyperplasia. Neointimal hyperplasia is mainly caused by an injury to the ...endothelial layer of the blood vessel followed by the proliferation of smooth muscle cells into the lumen of the blood vessel. To address this, we designed a magnetically-guided drug delivery system to locally deliver heparin to a stented artery. The nanoparticles were synthesized, characterized, and tested on relevant human cell lines.The particles were non-toxic to human smooth muscle cells, endothelial cells, and fibroblasts. They reduced the proliferation of the smooth muscle cells and increased the proliferation of endothelial cells at concentrations as low as 10 μg/mL. The particles also shifted the smooth muscle cells from their synthetic phenotype to their contractile phenotype.The capture of the nanoparticles by the stent struts, under relevant magnetic field and blood velocity was modeled using COMSOL Multiphysics. The coronary artery was modeled using a 2D axisymmetric model with stainless steel stent struts. A Magnetic field of 1 T was applied to magnetize the stent struts. Three different strut geometries were compared for their effect of the capture efficiency. The model had a capture efficiency 0f 34–42%, which is comparable to models using the same particle sizes.Ex vivo organ culture studies using porcine right coronary arteries were performed. The arteries were conditioned either statically in cell culture flasks or dynamically in an organ culture bioreactor. Nanoparticles reduced intimal thickening in and expressed contractile properties in the treated arteries compared to the controls.We were successfully able to synthesize heparin-coated magnetic nanoparticles and achieve high heparin loading. Particle capture efficiency around the stent in the ex vivo porcine artery model was found to be similar to that predicted by the computational model. Consistent with the prior results of systemic heparin delivery, the nanoparticles reduce the proliferation and dedifferentiation of vascular smooth muscle cells while promoting endothelialization, both in vitro and ex vivo. Thus, these particles may be a promising treatment option for neointimal hyperplasia..
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