肝血管走行改変と遺伝子治療による全膵機能再生の試み（第9回基礎・臨床融合の学内共同研究発表会）（抄録）

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  • Regeneration of a whole pancreatic function by a bloodstream modification and a specific gene transfer to the liver
  • カンケッカン ソウコウ カイヘン ト イデンシ チリョウ ニ ヨル ゼンスイ キノウ サイセイ ノ ココロミ （ダイ 9カイ キソ リンショウ ユウゴウ ノ ガクナイ キョウドウ ケンキュウ ハッピョウカイ）（ショウロク）

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type:Departmental Bulletin Paper

It has been reported that both pancreatic transplantation and islet cell transplantation are beneficial for patients following anextensive pancreatectomy and for patients who have type 1 diabetes mellitus. However, after transplantation, these patientsexperience the side effects of immunosuppressants and the rejection response. A new therapy to replace transplantation forpancreatic insufficiency is strongly desired. We are seeking a method to regenerate complete pancreatic function using the liver,because the liver and pancreas have the same embryological origin. In our previous studies, we produced a virus vector withthe pdx-1 gene, which is well known to be a master gene for pancreatic differentiation, cloned into the helper-dependentadenovirus, and we then administered it to diabetic mice. Although we found cells that produced both insulin and trypsin in theliver portal area, these mice died of fulminant hepatitis because of the pancreatic exocrine enzyme produced by the regeneratedcells. Therefore, we think that changing the mode of administration from the tail vein to the bile duct in retrograde fashion topart of the liver might prevent the onset of hepatic failure. The most important difference between the liver and pancreas is thatthe liver receives its blood supply from the portal vein. To regenerate a pancreas in the liver, we observed that changesoccurred in the liver after ligation of the right portal vein. Surprisingly, cell clusters that produced both insulin and trypsin wereobserved, but these cells were undifferentiated. These results suggest that modification of blood flow is necessary for thedifferentiation of the pancreas, and gene therapy is also needed for maturation to pancreatic cells. We are trying to regeneratecomplete pancreatic function in the liver as a therapy to replace transplantation for pancreatic insufficiency.

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