Neurosurgery Foundation, 55 Claverick Str,, Providence, RI 02903, USA.
Fluids Barriers CNS. 2011 May 17;8:18. doi: 10.1186/2045-8118-8-18.
Neuropeptides may have considerable potential in the treatment of acute and chronic neurological diseases. Encapsulated genetically engineered cells have been suggested as a means for sustained local delivery of such peptides to the brain. In our experiments, we studied human mesenchymal stem cells which were transfected to produce glucagon-like peptide-1 (GLP-1).
Cells were packed in a water-permeable mesh bag containing 400 polymeric microcapsules, each containing 3000 cells. The mesh bags were either transplanted into the subdural space, into the brain parenchyma or into the cerebral ventricles of the cat brain. Mesh bags were explanted after two weeks, and cell viability, as well as GLP-1 concentration in the cerebrospinal fluid (CSF), was measured.
Viability of cells did not significantly differ between the three implantation sites. However, CSF concentration of GLP-1 was significantly elevated only after ventricular transplantation with a maximum concentration of 73 pM (binding constant = 70 pM).
This study showed that ventricular cell-based delivery of soluble factors has the capability to achieve concentrations in the CSF which may become pharmacologically active. Despite the controversy about the pharmacokinetic limitations of ventricular drug delivery, there might be a niche in this for encapsulated cell biodelivery of soluble, highly biologically-effective neuropeptides of low molecular weight like GLP-1.
神经肽在治疗急性和慢性神经疾病方面具有很大的潜力。有人提出，包封的基因工程细胞是将此类肽持续局部递送至大脑的一种手段。在我们的实验中，我们研究了转染以产生胰高血糖素样肽-1 (GLP-1)的人间质干细胞。
将细胞包装在水可渗透的网袋中，每个网袋中含有 400 个聚合物微胶囊，每个微胶囊中含有 3000 个细胞。网袋要么被移植到硬脑膜下腔，要么被移植到猫脑的脑实质中，要么被移植到脑室内。两周后取出网袋，测量细胞活力以及脑脊液 (CSF)中的 GLP-1 浓度。
三种植入部位的细胞活力没有显著差异。然而，只有在脑室移植后，CSF 中的 GLP-1 浓度才显著升高，最高浓度为 73 pM（结合常数=70 pM）。
这项研究表明，基于脑室的可溶性因子输送具有使 CSF 中达到可能具有药理活性的浓度的能力。尽管关于脑室药物输送的药代动力学限制存在争议，但对于封装的细胞生物输送低分子量、生物活性高的可溶性神经肽（如 GLP-1），可能会有一个利基市场。
