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    Application of shear flow stress to chondrocytes or chondrocyte stem cells to produce cartilage
    2.
    发明授权
    Application of shear flow stress to chondrocytes or chondrocyte stem cells to produce cartilage 失效
    剪切流应力对软骨细胞或软骨细胞干细胞产生软骨的应用

    公开(公告)号：US5928945A

    公开(公告)日：1999-07-27

    申请号：US753104

    申请日：1996-11-20

    Applicant: Dror Seliktar ,  Noushin Dunkelman ,  Alvin Edward Peterson ,  Ronda Elizabeth Schreiber ,  Jane Willoughby ,  Gail K. Naughton

    Inventor： Dror Seliktar ,  Noushin Dunkelman ,  Alvin Edward Peterson ,  Ronda Elizabeth Schreiber ,  Jane Willoughby ,  Gail K. Naughton

    IPC: C12M3/00 ,  C12M3/02 ,  C12M3/04 ,  C12N5/00 ,  C12N5/077 ,  C12N11/02 ,  C12N5/06 ,  C12N3/00 ,  C12N5/08 ,  C12N11/00

    CPC classification number: C12N5/0655 ,  C12M21/08 ,  C12M25/14 ,  C12M35/04

    Abstract: Mammalian cells capable of producing cartilage are cultured under a shear flow stress of about 1 to about 100 dynes/cm.sup.2 to produce artificial cartilage for surgical transplantation to replace damaged or missing cartilage. Shear flow stressed cells display enhanced maintenance of chondrocyte phenotype and produce an extracellular matrix containing an enhanced ratio of type II collagen to type I collagen. The cells may be chondrocytes, chondrocyte stem cells or cells such as myoblasts or fibroblasts that transdifferentiate into chondrocytes. A bioreactor is used containing a growth chamber having a substrate on which the cells capable of producing cartilage are attached, and means for applying relative movement between a liquid culture medium and the substrate to provide the shear flow stress. The substrate may be a scaffold, or a nonporous surface such as the surface of a rotatable drum or disc, or the surface of a static plate that supports cell growth in a monolayer. Cartilage is produced by covering the substrate with a liquid growth medium, inoculating into the medium cells capable of producing cartilage, allowing the cells to attach to the substrate, applying and maintaining relative movement between the growth medium and the cells to provide the shear flow stress to produce shear flow stressed cells, and culturing the shear flow stressed cells to produce cartilage.

    Abstract translation: 能够产生软骨的哺乳动物细胞在约1至约100达因/平方厘米的剪切流动应力下培养以产生用于外科移植的人造软骨以替代损坏或缺失的软骨。 剪切流应力细胞表现出增强的软骨细胞表型的维持，并产生含有II型胶原与I型胶原蛋白比例增加的细胞外基质。 细胞可能是软骨细胞，软骨细胞干细胞或细胞如分化成软骨细胞的成肌细胞或成纤维细胞。 使用包含生长室的生物反应器，所述生长室具有附着有能够产生软骨的细胞的基底，以及用于在液体培养基和基底之间施加相对运动以提供剪切流动应力的装置。 基底可以是支架或无孔表面，例如可旋转的鼓或盘的表面，或支撑单层细胞生长的静态板的表面。 通过用液体生长培养基覆盖基质来生产软骨，接种到能够产生软骨的培养基细胞中，使细胞附着到基质上，施加和保持生长培养基和细胞之间的相对运动以提供剪切流应力 产生剪切流应力细胞，并培养剪切流应力细胞产生软骨。

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