Reconstruction of pancreatic islet by duct cell transplantation

导管细胞移植重建胰岛

• 批准号: 13557003
• 负责人: YAMASHINA Shohei
• 金额: $ 8.77万
• 依托单位: Kitasato University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13557003/
• 关键词: Diabetes mellitus; Pancreas; Islet; Duct; Transplantation; Stem cell; Regeneration medicine; ランゲルハンス島

Development of model system was intended to reconstruct pancreatic islet tissue by the transplantation of ductal cells. Summary of the results are as follows;1. Purification and transplantation of ductal cellsSeveral methods were compared to purify the duct cells from rat pancreas, and collagenase digestion after cutting into small pieces by razor blade was found to be a superior method. Purified cells were transplanted into subcapsular space of a kidney. As a result, small tubuloacinar structures could be developed 2-4weeks after the transplantation into nude mouse, however, the graft made little progress with the size after that. CCK seemed only minimal effect to induce growth of graft, although CCK was found to stimulate regeneration of pancreas after 90% pancreatectomy.2. Analysis of cellular differentiation in the graftTubuloacinar structure was too small to make serial section, since determination of cellular differentiation was quite difficult by immunohistochemical method. However, in vivo study during regeneration after 90% pancreatectomy, it was demonstrated that the centroacinar cells were progenitor of endocrine cells as well as acinar cells. A method should be developed to purify centroacinar cells in future, and the cells could be applied for successful transplantation.3.Transplantation to DM rat and clinical applicationTransplantation of duct cells into spontaneous DM rat produced similar results to that stated above, since reproducible discussion was difficult. Collection of information is being continued toward the development of new drug by application of the transplantation method.

模型系统的开发旨在通过导管细胞移植重建胰岛组织。研究结果总结如下： 1．导管细胞的纯化与移植比较了几种纯化大鼠胰腺导管细胞的方法，发现用刀片切成小片后进行胶原酶消化是一种更优越的方法。纯化的细胞被移植到肾脏的被膜下空间。结果，移植到裸鼠体内2-4周后即可发育出小的管状腺泡结构，但此后移植物的尺寸几乎没有进展。尽管CCK在90%胰腺切除术后发现可以刺激胰腺再生，但CCK对诱导移植物生长的作用似乎很小。 2．移植管腺泡结构中的细胞分化分析太小，无法进行连续切片，因为通过免疫组织化学方法测定细胞分化相当困难。然而，90%胰腺切除术后再生过程中的体内研究表明，腺泡中心细胞是内分泌细胞和腺泡细胞的祖细胞。今后应开发一种纯化腺泡中心细胞的方法，以用于成功移植。3. DM大鼠移植及临床应用导管细胞移植到自发性DM大鼠中产生与上述相似的结果，但重复性讨论困难。正在继续收集信息，以利用移植方法开发新药。

项目成果

Kimiya Handa, Tetsutaro Suzuki, Keiko Hayashi, Tsuyoshi Takahashi, Akira Kakita, Shohei Yamashina: "Effect of cholecystokinin-A receptor antagonist on rat pancreas after partial pancreatectomy."Acta Histochem.Cytochem.. 37(1). 31-38 (2004)

Kimiya Handa、Tetsutaro Suzuki、Keiko Hayashi、Tsuyoshi Takahashi、Akira Kakita、Shohei Yamashina：“胆囊收缩素-A 受体拮抗剂对部分胰腺切除术后大鼠胰腺的影响”。Acta Histochem.Cytochem.. 37(1)。

Kimiya Handa, 他5名: "Effect of cholecystokinin-A receptor antagonist on rat pancreas after partial pancreatectomy."Acta.Histochem.Cytochem.. 37(1). 31-38 (2004)

Kimiya Handa 等 5 人：“部分胰腺切除术后胆囊收缩素 A 受体拮抗剂对大鼠胰腺的影响”Acta.Histochem.Cytochem.. 37(1) (2004)。

Keiko Yokoyama-Hayashi, 他3名: "Expression of PGP 9.5 in ductal cells of the rat pancreas during development and regeneration : Can it be a marker for pancreatic progenitor cells?"Endocrine J.. 49(1). 61-74 (2002)

Keiko Yokoyama-Hayashi 等 3 人：“大鼠胰腺导管细胞在发育和再生过程中 PGP 9.5 的表达：它可以成为胰腺祖细胞的标记吗？”Endocrine J.. 49(1) ( 2002）

Tetsutaro Suzuki, Yuichi Kadoya, Yuichi Satoh, Kimiya Handa, Tsuyoshi Takahashi, Akira Kakita, Shohei Yamashina: "Expression of pancreatic endocrine markers in centroacinar cells of normal and regenerating rat pancreas : their possible transformation to e

Tetsutaro Suzuki、Yuichi Kadoya、Yuichi Satoh、Kimiya Handa、Tsuyoshi Takahashi、Akira Kakita、Shohei Yamashina：“正常和再生大鼠胰腺中央腺泡细胞中胰腺内分泌标记物的表达：它们可能转化为 e

K.Yokoyama-Hayashi 他: "Expression of PGP9.5 in Ductal Cells of the Rat Pancreas during Development and Regeneration"Endocrine J. 49(1). 61-74 (2002)

K. Yokoyama-Hayashi 等人：“发育和再生过程中大鼠胰腺导管细胞中 PGP9.5 的表达”Endocrine J. 49(1) (2002)。