The Applications Of Human IPS Cells And Exosomes In Gastric Cancer Therapy

Gastric cancer is one of the most common gastrointestinal malignancies in the world.China is one of the countries with high gastric cancer incidence.According to the "2015 China Cancer Statistics" released by China Cancer Registration Center,about 679,000 new cases and 498,000 deaths gastric cancer cases occur in 2015,which means about one gastric cancer patient died per minute.At present,surgical treatment,radiotherapy and chemotherapy are the three main therapeutic methods of gastric cancer.In addition,hyperthermia and biological therapy are also used in gastric cancer therapy.Nanotechnology is one of the three cutting-edge areas,the combination of nanotechnology with biology or medicine will greatly promote the development of disease diagnosis and treatment,especially in cancer research.In this study,MMC pre-treated human pluripotent stem cells are used as a safe gold nanorod vehicle for gastric cancer thermal therapy.In addition,we explored the feasibility of applying free exosomes in gastric cancer therapy and established an effective exosomes isolated method.The main research contents as follows:(1)1 ?g/ml mitomycin C was used to treat human iPS cells which loading with gold nanorods in advance.Both in vitro and in vivo experiments demonstrated the pre-treated cells still have tumor tropism ability.The pre-treated iPS cells with nanorods were injected in tumor bearing mice by tail intravenous.After 3 days,enhanced photothermal therapy results have achieved.Seven days later,the mice organs were extracted and the iPS cells were found in normal organs such as liver,lung and kidney etc.But no iPS cell survived in organs by the treatment of mitomycin C.Our study achieved the purpose of using iPS cells as a safe gold nanorod vehicle in targeted gastric cancer photothermal therapy,which will provide a new insight in using stem cells as a safe carrier for cancer therapy.(2)The exosomes have been used in tumor therapy widely and the therapeutic effects were mainly achieved by loading drugs or biomolecules.In this process,the researchers need to consider the choice of drugs,the drug loading ways and drug loading efficiency.In this study,we have found that two kinds of free exosomes can be used for gastric cancer cells treatment.iPS exosomes can inhibit the proliferation of gastric cancer cell line MGC803,multiple proteins in the exosomes may participate the process.Cytokine induced killer(CIK)exosomes can kill MGC803 and the mechanism was the several cytokines detected in the exosomes.Next,a new method based on dialysis was established to isolate exosomes and the effectiveness of this method was demonstrated by isolating urine and CIK cell exosomes.The method has the advantages of simple operation,high purity and low cost etc.The discovery of two types of exosomes,will broaden the prospect of gastric cancer treatment by exosomes and the new method will promote the clinical applications of exosomes.