【Symposium 3】 A Method for Evaluating Intravascular Stent in a Miniature Pig Model S3-1
○ Osamu Ishikawa Department of Neurosurgery, The University of Tokyo
In recent years, arteriosclerotic diseases such as myocardial or cerebral infarction have increased rapidly. Stent placement technique has been used as a medical treatment for arteriosclerotic disease, but the problems of in-stent restenosis and stent thrombosis are still unresolved. We conducted the animal study in order to invest the efficacy and safety of the coating stent toward to bare-metal stent and drug-eluting stent which were mainly used in recent years. Since now, stent have been developed by an animal study using a pig coronary or carotid artery. Pathological specimens have been mainly evaluated, but the time course of morphological changes was not considered. So, we tried to evaluate the time course of the morphological changes after stent placement by repeated intravascular interventional analysis. Miniature pigs were used because the growth of their
body and organ is not rapid and the size of vessels is as same as that of human. The catheter was inserted via common carotid artery, and different type of stents, as many as 4 to 6 stents, were implanted per one animal. The time course of in-stent restenosis and stent thrombosis were serially observed every 2 weeks using angiogram and intravascular ultrasound, and finally the animal was sacrificed and the targeted vessels was harvested at 12 weeks for pathological evaluation. As the result, serial morphological changes of the implanted stent were exactly observed during study period. And, in-stent restenosis and stent thrombosis of the coating stent were significantly smaller than those of bare-metal or drug-eluting stent. It is considered this experimental model can be applied to the various studies about intravascular devices.
Cell therapy for Parkinson’ s disease with induced pluripotent stem cells S3-2
○ Asuka Morizane, Jun Takahashi Department of Biological Repair, Field of Clinical Application, Institute for Frontier Medical Sciences, Kyoto University
The innovation of induced pluripotent stem cells （iPSCs）and previous embryonic stem cell（ESC） technologies are drawing attention to their application for regenerative medicine. Parkinson’ s disease is one of the most promising target diseases because of the history of fetal nigral transplantation in clinics. As an additional treatment to medication, cell therapy with aborted fetal tissues has been performed since 1980’ s. However, the limited supply of donor source and the unstable quality of the cells prevent this therapy from becoming standard. The technology of iPSCs offers a limitless and more advantageous donor source than aborted embryos. One of the advantages is possibility of preparing immunologically compatible donor cells from selfderived or allogeneic iPSCs. We are preparing a clinical trial on the transplantation of dopamine
neural progenitors differentiated from iPSCs. We have successfully established a protocol for donor induction with clinically compatible grade and have transplanted these neurons into PD models of mice, rats, and cynomolgus monkeys as preclinical studies. Typical PD animal models have their midbrain-striatum dopamine systems selectively destroyed by neurotoxins, such as 6-hydroxydopamine （6-OHDA） for rats and 1,2,3,6-tetrahydropyridine（MPTP）for monkeys and mice. We confirmed that donor cells derived from iPS cells improved the motor symptoms of those model animals and that the grafted neurons survive and stretch fibers to the host striatum. Imaging study with MRI and PET scan also showed the graft function without any side effect such as tumor formation. This result ensured the safety and effectiveness of cell therapy for PD with iPS cell technology.
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Anesthesia and perioperative care of the large animal by the research assistant S3-3
○ Hajime Fukuda Fukushima Medical Device Industry Promotion Agency
I was engaged in the animal experiment using the large animal such as miniature pigs and monkeys as the research assistant in a research organization and a university from 2007. The animal experiment that I was engaged in is an experiment to create disease model using surgery technique such as myocardial infarction model or an experiment to observe an animal using PET, CT, MRI. These experiments put animals under general anesthesia and are carried out.
There are three main roles of the research assistant. The first is the acclimation of the animals before the experiment start, the second is anesthesia introduction to animals and other experiment support, and the third is postoperative care to postoperative animals. Today, I introduce what I really experienced from research assistant’ s role around anesthesia and a place about perioperative care.
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2017/05/17 16:29
○ Osamu Ishikawa Department of Neurosurgery, The University of Tokyo
In recent years, arteriosclerotic diseases such as myocardial or cerebral infarction have increased rapidly. Stent placement technique has been used as a medical treatment for arteriosclerotic disease, but the problems of in-stent restenosis and stent thrombosis are still unresolved. We conducted the animal study in order to invest the efficacy and safety of the coating stent toward to bare-metal stent and drug-eluting stent which were mainly used in recent years. Since now, stent have been developed by an animal study using a pig coronary or carotid artery. Pathological specimens have been mainly evaluated, but the time course of morphological changes was not considered. So, we tried to evaluate the time course of the morphological changes after stent placement by repeated intravascular interventional analysis. Miniature pigs were used because the growth of their
body and organ is not rapid and the size of vessels is as same as that of human. The catheter was inserted via common carotid artery, and different type of stents, as many as 4 to 6 stents, were implanted per one animal. The time course of in-stent restenosis and stent thrombosis were serially observed every 2 weeks using angiogram and intravascular ultrasound, and finally the animal was sacrificed and the targeted vessels was harvested at 12 weeks for pathological evaluation. As the result, serial morphological changes of the implanted stent were exactly observed during study period. And, in-stent restenosis and stent thrombosis of the coating stent were significantly smaller than those of bare-metal or drug-eluting stent. It is considered this experimental model can be applied to the various studies about intravascular devices.
Cell therapy for Parkinson’ s disease with induced pluripotent stem cells S3-2
○ Asuka Morizane, Jun Takahashi Department of Biological Repair, Field of Clinical Application, Institute for Frontier Medical Sciences, Kyoto University
The innovation of induced pluripotent stem cells （iPSCs）and previous embryonic stem cell（ESC） technologies are drawing attention to their application for regenerative medicine. Parkinson’ s disease is one of the most promising target diseases because of the history of fetal nigral transplantation in clinics. As an additional treatment to medication, cell therapy with aborted fetal tissues has been performed since 1980’ s. However, the limited supply of donor source and the unstable quality of the cells prevent this therapy from becoming standard. The technology of iPSCs offers a limitless and more advantageous donor source than aborted embryos. One of the advantages is possibility of preparing immunologically compatible donor cells from selfderived or allogeneic iPSCs. We are preparing a clinical trial on the transplantation of dopamine
neural progenitors differentiated from iPSCs. We have successfully established a protocol for donor induction with clinically compatible grade and have transplanted these neurons into PD models of mice, rats, and cynomolgus monkeys as preclinical studies. Typical PD animal models have their midbrain-striatum dopamine systems selectively destroyed by neurotoxins, such as 6-hydroxydopamine （6-OHDA） for rats and 1,2,3,6-tetrahydropyridine（MPTP）for monkeys and mice. We confirmed that donor cells derived from iPS cells improved the motor symptoms of those model animals and that the grafted neurons survive and stretch fibers to the host striatum. Imaging study with MRI and PET scan also showed the graft function without any side effect such as tumor formation. This result ensured the safety and effectiveness of cell therapy for PD with iPS cell technology.
― S13 ―
JALAS英文版.indd 13
2017/05/17 16:29
Anesthesia and perioperative care of the large animal by the research assistant S3-3
○ Hajime Fukuda Fukushima Medical Device Industry Promotion Agency
I was engaged in the animal experiment using the large animal such as miniature pigs and monkeys as the research assistant in a research organization and a university from 2007. The animal experiment that I was engaged in is an experiment to create disease model using surgery technique such as myocardial infarction model or an experiment to observe an animal using PET, CT, MRI. These experiments put animals under general anesthesia and are carried out.
There are three main roles of the research assistant. The first is the acclimation of the animals before the experiment start, the second is anesthesia introduction to animals and other experiment support, and the third is postoperative care to postoperative animals. Today, I introduce what I really experienced from research assistant’ s role around anesthesia and a place about perioperative care.
― S14 ―
JALAS英文版.indd 14
2017/05/17 16:29
