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    TRANSDIFFERENTIATION OF PANCREATIC ACINAR CELLS
    5.
    发明授权
    TRANSDIFFERENTIATION OF PANCREATIC ACINAR CELLS 有权
    胰腺腺泡细胞转分化

    公开(公告)号：EP1463801B1

    公开(公告)日：2008-08-13

    申请号：EP03700250.8

    申请日：2003-01-10

    申请人： McGill University

    发明人： ROSENBERG, Lawrence

    IPC分类号： C12N5/00

    CPC分类号： C12N5/0676 ,  A61K38/1709 ,  C12N2501/998

    摘要： Induction of β-cell neogenesis has been associated with ductal epithelium, however ≈80% of the pancreas is composed of acinar cells. Surprisingly, pancreatic acinar cells contribute to β-cell neogenesis. Partial duct obstruction (PDO) of the pancreas is a known inducer of β-cell neogenesis leading to expansion of β-cell mass, and the effect appears to be mediated by INGAP, an acinar cell protein originally identified in the regenerating hamster pancreas. We examined the effects of PDO on the incorporation of tritiated thymidine by acinar and β-cells of the pancreas in female Syrian hamsters. A single dose of tritiated thymidine was administered to all animals 2 weeks after PDO. Animals were then sacrificed at 1 hr, or at 6 weeks post-injection. Tritiated thymidine incorporation into acinar cells was highest at 2 weeks after PDO and declined at 8 weeks after PDO. Incorporation of tritiated thymidine into β-cells was inversely related to that observed in acinar cells. Two weeks following PDO, β-cell tritiated thymidine uptake was relatively low and it increased significantly at 8 weeks after PDO, consistent with β-cell neogenesis from an acinar cell origin. Electron microscopy demonstrated cells with both zymogen and endocrine granules, further suggesting acinar to endocrine cell transdifferentiation. In a second experiment, hamsters were administered either a pentadecapeptide of INGAP protein or an equivalent volume of saline for 10 days. There was a 2-fold increase in the number of extra-islet acinar-associated β-cell clusters in the INGAP peptide-treated hamsters resulting in a 2.8-fold increase in the overall extra-islet β-cell mass. Acinar-to-β-cell differentiation provides an alternate pathway to β-cell neogenesis; INGAP peptide plays a significant role in this process.

    TRANSDIFFERENTIATION OF PANCREATIC ACINAR CELLS
    6.
    发明公开
    TRANSDIFFERENTIATION OF PANCREATIC ACINAR CELLS 有权
    胰腺腺泡细胞转分化

    公开(公告)号：EP1463801A2

    公开(公告)日：2004-10-06

    申请号：EP03700250.8

    申请日：2003-01-10

    申请人： McGill University

    发明人： ROSENBERG, Lawrence

    IPC分类号： C12N5/00

    CPC分类号： C12N5/0676 ,  A61K38/1709 ,  C12N2501/998

    摘要： Induction of β-cell neogenesis has been associated with ductal epithelium, however ≈80% of the pancreas is composed of acinar cells. Surprisingly, pancreatic acinar cells contribute to β-cell neogenesis. Partial duct obstruction (PDO) of the pancreas is a known inducer of β-cell neogenesis leading to expansion of β-cell mass, and the effect appears to be mediated by INGAP, an acinar cell protein originally identified in the regenerating hamster pancreas. We examined the effects of PDO on the incorporation of tritiated thymidine by acinar and β-cells of the pancreas in female Syrian hamsters. A single dose of tritiated thymidine was administered to all animals 2 weeks after PDO. Animals were then sacrificed at 1 hr, or at 6 weeks post-injection. Tritiated thymidine incorporation into acinar cells was highest at 2 weeks after PDO and declined at 8 weeks after PDO. Incorporation of tritiated thymidine into β-cells was inversely related to that observed in acinar cells. Two weeks following PDO, β-cell tritiated thymidine uptake was relatively low and it increased significantly at 8 weeks after PDO, consistent with β-cell neogenesis from an acinar cell origin. Electron microscopy demonstrated cells with both zymogen and endocrine granules, further suggesting acinar to endocrine cell transdifferentiation. In a second experiment, hamsters were administered either a pentadecapeptide of INGAP protein or an equivalent volume of saline for 10 days. There was a 2-fold increase in the number of extra-islet acinar-associated β-cell clusters in the INGAP peptide-treated hamsters resulting in a 2.8-fold increase in the overall extra-islet β-cell mass. Acinar-to-β-cell differentiation provides an alternate pathway to β-cell neogenesis; INGAP peptide plays a significant role in this process.

    PLATFORM FOR THE DIFFERENTIATION OF CELLS
    7.
    发明公开
    PLATFORM FOR THE DIFFERENTIATION OF CELLS 审中-公开
    平台对细胞的分化

    公开(公告)号：EP1144595A2

    公开(公告)日：2001-10-17

    申请号：EP00903442.2

    申请日：2000-02-02

    申请人： McGILL UNIVERSITY

    发明人： ROSENBERG, Lawrence

    IPC分类号： C12N5/08 ,  A61K35/39 ,  A61P5/48

    CPC分类号： C12N5/0676 ,  A61K35/12 ,  C12N2501/105 ,  C12N2501/13 ,  C12N2501/33 ,  C12N2501/58 ,  C12N2506/22

    摘要： The present invention relates to an in vitro method for islet cell expansion, which comprises the steps of: a) preparing dedifferentiated cells derived from cells in or associated with post-natal islets of Langerhans; b) expanding the dedifferentiated cells; and c) inducing islet cell differentiation the expanded cells of step b) to become insulin-producing cells.

    摘要翻译： 本发明涉及用于胰岛细胞扩增的体外方法，其包括以下步骤：a）制备来源于朗格汉斯出生后胰岛中或与之相关的细胞的去分化细胞; b）扩大去分化细胞; 和c）诱导胰岛细胞分化步骤b）的扩增细胞以变成产生胰岛素的细胞。

    PANCREATIC SMALL CELLS AND USES THEREOF
    8.
    发明公开
    PANCREATIC SMALL CELLS AND USES THEREOF 审中-公开
    胰腺小细胞及其应用

    公开(公告)号：EP1427814A1

    公开(公告)日：2004-06-16

    申请号：EP02764416.0

    申请日：2002-09-09

    申请人： McGill University

    发明人： ROSENBERG, Lawrence ,  PETROPAVLOVSKAIA, Maria

    IPC分类号： C12N5/06

    CPC分类号： C12N5/0676 ,  A61K35/12 ,  C12N2510/02 ,  C12N2510/04

    摘要： The present invention provides mammalian pancreatic progenitor cells ("small cells") and methods for their isolation and propagation. The pancreatic small cells are derived from adult pancreatic tissue and are characterised by their small size. The small cells are quiescent or undergo a very slow cell cycle when maintained in cell culture. Small cells secrete synaptophysin and islet hormones and are predominantly found in small, growing islets as small clusters. The present invention further provides for the use of the pancreatic small cells in transplantation and the treatment of diabetes mellitus, and for the genetic engineering of the small cells in order to produce recombinant proteins in vivo.

    MEDIUM FOR PREPARING DEDIFFERENTIATED CELLS
    9.
    发明公开
    MEDIUM FOR PREPARING DEDIFFERENTIATED CELLS 审中-公开
    培养基制备DEDIFFERENTIERTER细胞

    公开(公告)号：EP1224263A2

    公开(公告)日：2002-07-24

    申请号：EP00972511.0

    申请日：2000-10-27

    申请人： McGILL UNIVERSITY

    发明人： ROSENBERG, Lawrence

    IPC分类号： C12N5/06 ,  C12N5/08

    CPC分类号： C12N5/0676 ,  C12N2501/01 ,  C12N2501/11 ,  C12N2506/22

    摘要： The present invention relates to a medium for preparing dedifferentiated cells derived from post-natal islets of Langerhans. The medium comprises in a physiologically acceptable culture medium an effective amount of a solid matrix environment for a three-dimensional culture, a soluble matrix protein, and a first and a second factor for developing, maintaining and expanding the dedifferentiated cells. Such a medium may be used in an in vitro method for islet cell expansion.