Emerich D F, Salzberg H C
Department of Neuroscience, Alkermes, Inc, Cambridge, MA 02139, USA.
Cell Transplant. 2001 Jan-Feb;10(1):3-24.
Delivery of potentially therapeutic drugs to the brain is hindered by the blood-brain barrier (BBB), which restricts the diffusion of drugs from the vasculature to the brain parenchyma. One means of overcoming the BBB is with cellular implants that produce and deliver therapeutic molecules. Polymer encapsulation, or immunoisolation, provides a means of overcoming the BBB to deliver therapeutic molecules directly into the CNS region of interest. Immunoisolation is based on the observation that xenogeneic cells can be protected from host rejection by encapsulating, or surrounding, them within an immunoisolatory, semipermeable membrane. Cells can be enclosed within a selective, semipermeable membrane barrier that admits oxygen and required nutrients and releases bioactive cell secretions, but restricts passage of larger cytotoxic agents from the host immune defense system. The selective membrane eliminates the need for chronic immunosuppression of the host and allows the implanted cells to be obtained from nonhuman sources. In this review, cell immunoisolation for treating CNS diseases is updated from considerations of device configurations, membrane manufacturing and characterization in preclinical models of Alzheimer's and Huntington's disease.
血脑屏障(BBB)阻碍了潜在治疗药物进入大脑,它限制了药物从血管系统扩散到脑实质。克服血脑屏障的一种方法是使用能产生并递送治疗分子的细胞植入物。聚合物封装,即免疫隔离,提供了一种克服血脑屏障将治疗分子直接递送至中枢神经系统(CNS)目标区域的方法。免疫隔离基于这样的观察结果:通过将异种细胞封装或包裹在免疫隔离的半透膜内,可以保护它们免受宿主排斥。细胞可以被封闭在选择性半透膜屏障内,该屏障允许氧气和所需营养物质进入,并释放生物活性细胞分泌物,但限制宿主免疫防御系统中较大的细胞毒性剂通过。这种选择性膜消除了对宿主进行长期免疫抑制的需要,并允许植入细胞取自非人类来源。在本综述中,从阿尔茨海默病和亨廷顿病临床前模型中的装置配置、膜制造和表征等方面,对用于治疗中枢神经系统疾病的细胞免疫隔离进行了更新。