S. Yamaguchi1, Y. Maruya1, K. Kanetaka1, S. Kobayashi1, K. Hashiguchi2, K. Nakao2, A. Morinaga3, Y. Sakai4, S. Eguchi1 3Nagasaki University,School Of Engineering,Nagasaki, Nagasaki, Japan 1Nagasaki University,Department Of Surgery,Nagasaki, Nagasaki, Japan 2Nagasaki University,Department Of Gastroenterology And Hepatology,Nagasaki, Nagasaki, Japan 4Kyusyu University,Faculty Of Engineering,Fukuoka, FUKUOKA, Japan
Introduction:
The field of regenerative medicine with gastrointestinal organs is still developing. Delivery of cell sheets to target internal organs with no adverse events is difficult due to the sheets’ fragility and organ configuration as well as the potential for pneumoperitoneum. The purpose of the present study was to develop laparoscopic delivery devices that enable safe delivery and transplantation of cell sheets.
Methods:
Myoblast cells were isolated from four porcine muscle tissues and expanded and cultured on temperature-responsive dishes to form cell sheets (3cm). After two weeks, four pigs (15kg) underwent laparoscopic surgery and seven cell sheets were individually transplanted into the internal organs (Liver, small intestine and duodenum) using two types of newly developed laparoscopic delivery devices. The type 1 device consisted of porous silicon film. A rounded silicon device with a cell sheet on the tip was inserted into the abdominal space through a laparoscopic 12mm port and delivered to target organs after deployment.
The type 2 device stored the myoblast cell sheet inside the device by negative pressure for laparoscopic transplantation. The cell sheet was placed onto the top, which has a matrix of small holes. After insertion, the cell sheet was detached by applying compressed air from behind the cell sheet. Device insertion was performed through a laparoscopic port. The adherence of the cell sheets was confirmed by macroscopic and histopathological analysis after three days of the sheets’ transplantation into the porcine organ (type 1: n=5, type2; n=2).
Results:
Both the type 1 and type 2 devices allowed successful transplantation of all cell sheets with a high success rate (100% each). There were no adverse incidents with either method. The type 2 device enabled insertion perhaps to the pigs’ organs with a shorter procedure time than the type 1 device (3 minutes for the type 1 device vs 1 minute for the type 2 device). Macroscopic and histopathological analysis showed that the cell sheets successfully attached to the target organs in 100% of cases in both groups.
Conclusion:
Through this study, we confirmed that the novel laparoscopic delivery device enables safe and effective cell sheet transplantation onto targeted organs with no adverse events. These results support the feasibility of the device for a clinical trial.
