Changes in ionizing radiation dose rate affect cell cycle progression in adipose derived stem cells.

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.

In vitro studies of heparin-coated magnetic nanoparticles for use in the treatment of neointimal hyperplasia.

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.