초록 ▼

췌장소도이식은 인슐린 결핍성 당뇨병의 새로운 치료법 중에서 가장 생리적인 방법이지만 당뇨병환자에게 평생 인슐린 투여와 이식에 따른 면역억제제 치료가 필요치 않도록 하기 위해서는 췌장소도 이식술의 방법이 계속 연구개발 되어야 한다. 이런 면에서 충분한 양의 췌도세포를 확보하고 이식 후 면역기전으로 인한 췌도세포의 손실을 줄이는 방법이 췌장소도이식술에서 가장 중요한 성공요소이다. 이에 따라 본 연구팀은 췌장소도이식에 있어 충분한 양의 췌장소도를 얻기 위하여 동물 및 사람의 췌도세포의 무균적 대량분리를 위한 분리법 개선과 자동화를 이룩하

췌장소도이식은 인슐린 결핍성 당뇨병의 새로운 치료법 중에서 가장 생리적인 방법이지만 당뇨병환자에게 평생 인슐린 투여와 이식에 따른 면역억제제 치료가 필요치 않도록 하기 위해서는 췌장소도 이식술의 방법이 계속 연구개발 되어야 한다. 이런 면에서 충분한 양의 췌도세포를 확보하고 이식 후 면역기전으로 인한 췌도세포의 손실을 줄이는 방법이 췌장소도이식술에서 가장 중요한 성공요소이다. 이에 따라 본 연구팀은 췌장소도이식에 있어 충분한 양의 췌장소도를 얻기 위하여 동물 및 사람의 췌도세포의 무균적 대량분리를 위한 분리법 개선과 자동화를 이룩하고 분리된 췌도세포의 냉동보관법을 확립하였다. 그리고, 인간의 췌장소도를 상기방법으로 분리하여 환자 9명에게 동종이식 또는 자가이식함으로써 당뇨병을 치료하거나 예방할 수 잇게 되었다. 한편, 백서 및 사람의 췌도세포에 처치된 IGF-1이 세포의 증식을 촉진하고 인슐린 분비를 증강하며 사이토카인의 세포독성작용을 예방함으로써 자연사 억제작용이 있음을 확인하였다. 그러나 췌도세포에 처치된 PPAR-$\gamma$는 췌도세포의 증식이나 인슐린 분비능에 영향을 주지 못하였다. 췌관세포의 배양에서는 일부 췌도세포로의 분화를 확인하여, 새로운 췌도 이식원으로서의 가능성을 높였다.

Abstract ▼

In the first year, we realized automation by improving process of pancreatic islet differentiation of large animal in an effort to establish base technology necessary in massive isolation, aseptic isolation and transplantation of human pancreatic islet and applied it into the isolation process of hu

In the first year, we realized automation by improving process of pancreatic islet differentiation of large animal in an effort to establish base technology necessary in massive isolation, aseptic isolation and transplantation of human pancreatic islet and applied it into the isolation process of human pancreatic islet. We examined the role of PPAR-$\gamma$ in proliferation and insulin secretion of INS-1 cell line of rat, evaluated proliferation and insulin secretion by IGF-1 in INS-1 cell line and pancreatic islet cell of rat, and evaluated whether or not there is anti-apoptotic effect by IGF-1. We gained technique to select and cultivate only ductal cell of porcine pancreatic islet subject to massive isolation in order to obtain technique of pancreatic ductal cell culture. As a collaboration task, we tried to synthesize sulfonylurea polymer and synthesize thermosensitive hydrogel for intercellular matrix, but it was unavoidable to close the performance of task in pancreatic islet and polymer matrix system, which was a collaboration task, due to an emigration of a person in charge of such collaboration research. Instead, we focused on transplantation and proliferation of pancreatic islet, a core assignment. In the second year, we on the basis of established technique to pancreatic islet transplantation, conducted pancreatic islet autotransplantation for patients who were given total pancreatectomy or subtotal pancreatectomy due to chronic pancreatitis and benign pancreatic tumor, and executed pancreatic islet allotransplantation to the type 1 DM patient. In order to extablish large scale storage facilities for transplantation following isolation of human pancreatic islet, we established cryopreservation method and studied the role of PPAR-$\gamma$ toward insulin secretion and proliferation in human pancreatic islet and apoptosis. We evaluated proliferation and insulin secretion, and anti-apoptotic effect by IGF-1 in human pancreatic islet cell, inducing differentiation to pancreatic islet through human ductal cell culture, thereby trying to develop new pancreatic islet source. Lastly, with respect to the experiment on transplantation of pancreatic islet pre-treated of PPAR-$\gamma$ among the objective for the third year’s research and development, the contents on transplantation of pancreatic islet pre-treated of PPAR-$\gamma$ were deleted in that PPAR-$\gamma$ did not affect much insulin secretion and proliferation of pancreatic islet in practice. Instead, the objective was given to the execution of pancreatic islet transplantation subject to cryopreservation, which was expected to have an effect of long term preservation of pancreatic islet as well as immunosuppressant, and pancreatic islet transplantation differentiated from human and animal pancreatic ductal cell, and to the clinical application to human being on the basis of animal experiment of transplantation of pancreatic islet pre-treated of IGF-1. While the completion of animal experiment on pancreatic islet subject to artificial manipulation and animal experiment on pancreatic islet transplantation subject to cryopreservation confirmed its validity, more and more verification on the safety of artificially manipulated cell is required and there is no actual worldwide case of transplantation to human on the basis of such result. Moreover, a public hearing process is under progress in Korea to enact legal framework to this. In this regard, we modified the final objective as conducting a clinical application of pancreatic islet isolated purely in the current stage and proceeded with the research. The entire process of the research conducted by us is a part of a project, which should be proceeded for a long time. Thus, the more period and research is required to conduct a stable clinical application.

목차 Contents

• 제 1 장 연구개발과제의 개요...15
• 제 2 장 국내외 기술개발 현황...20
• 제 3 장 연구개발수행 내용 및 결과...27
• 제 4 장 목표달성도 및 관련분야에의 기여도...58
• 제 5 장 연구개발결과의 활용계획...60
• 제 6 장 연구개발과정에서 수집한 해외과학기술정보...61
• 제 7 장 참고문헌...63