Heparin-binding growth factor 1 induces the formation of organoid neovascular structures in vivo.
Heparin-binding growth factor 1 induces the formation of organoid neovascular structures in vivo.
复制标题
肝素结合生长因子 1 诱导体内类器官新生血管结构的形成。
DOI：
10.1073/pnas.86.20.7928
复制
发表时间：
1989
影响因子：
11.1
通讯作者：
Maciag,T
中科院分区：
文献类型：
--
作者：
Thompson,JA;Haudenschild,CC;Anderson,KD;DiPietro,JM;Anderson,WF;Maciag,T
现代分子生物学的前景之一是有机会在患者体内使用转基因人类细胞永久恢复先天性代谢缺陷。尽管已经有可能将基因导入哺乳动物细胞并控制其表达，但已证明难以将哺乳动物细胞作为修饰的遗传信息的载体导入宿主。没有足够的血管支持，选择性细胞的成功植入是无法实现的，这是整合和重建新生物功能的重要一步。虽然已经发现通过使用吸附到胶原基质的肝素结合生长因子1（HBGF-1）诱导特异性位点定向的新血管形成来部分解决该问题，但是这些植入物仅在短时间内（数周）起作用。我们现在报告的形成类器官新生血管结构使用聚四氟乙烯纤维涂有胶原蛋白和HBGF-1植入大鼠腹腔。类器官结构包含容易看到的血管腔和类似神经组织的非血管结构。还可以证明植入物上的血管系统与宿主的血管树是连续的。该特征用于证明类器官结构能够在纯合古恩大鼠中长时间（数月）维持植入的正常大鼠肝细胞的生物学功能，从而促进涉及递送新遗传信息的未来应用。
One of the promises of modern molecular biology has been the opportunity to use genetically modified human cells in a patient to permanently restore inborn errors of metabolism. Although it has been possible to introduce genes into mammalian cells and to control their expression, it has proven difficult to introduce mammalian cells as carriers of the modified genetic information into hosts. The successful implantation of selective cells cannot be achieved without adequate vascular support, an essential step toward integration and reconstitution of a new biological function. Although a partial solution to this problem has been found by inducing specific site-directed neovessel formation using heparin-binding growth factor 1 (HBGF-1) adsorbed to a collagen matrix, these implants function for only a short period (weeks). We now report the formation of organoid neovascular structures using polytetrafluoroethylene fibers coated with collagen and HBGF-1 implanted in the peritoneal cavity of the rat. The organoid structures contained readily visible vascular lumina and nonvascular structures that resemble nerve tissue. It was also possible to demonstrate that the vascular system on the implant is continuous with the vascular tree of the host. This feature was used to demonstrate that the organoid structures are capable of sustaining the biological function of implanted normal rat hepatocytes over long periods of time (months) in the homozygous Gunn rat, thereby facilitating future applications involving the delivery of new genetic information.