Development of a Transplantation Platform Technology Applicable for Improving Graft Survival in the Brain

一些神经退行性疾病，如帕金森氏病，部分特征是特定位置的特定亚型神经元丢失。因此，可以考虑替换这些细胞以恢复丢失的功能。随着大量改进的细胞来源(如诱导多能干细胞来源的神经元)的出现，现在是时候专注于克服移植过程中的瓶颈：移植物存活率低。移植后细胞存活率低仍然是移植成功的主要障碍，胎儿组织的存活率通常不到10%，干细胞的存活率也要低得多。DFG资助的这个项目(编号：NE2052/2-1)旨在从一个全新的和以前从未探索的角度解决这个问题：旨在改善移植后细胞存活的生物材料结构。在这个项目中，我们发现，尽管文献显示移植物核心严重缺乏氧气(缺氧)，但干细胞实际上可以在这些条件下很好地存活。我们假设这是由于细胞恢复到无氧呼吸途径所致。相反，我们已经证明葡萄糖是决定细胞存活的一个更关键的因素。到目前为止，还没有葡萄糖释放生物材料装置，所以这个项目续签申请资金来合成和表征这种材料。这将基于将葡萄糖封装在可生物降解的聚(β-氨基酯)网络中，使用微流控流动聚焦装置来创建能够通过小针头注射的均匀微球。根据Burkhard Jahnen博士的建议，最初的提案(要求四年供资)缩短为两年，并可能为剩余两年提出续展申请。在这个项目上工作的学生非常努力和富有成效(已经在写第一作者的手稿)，我们现在正在申请资金，以将上述重要方面添加到他的博士项目中。

Some neurodegenerative diseases, such as Parkinson’s disease, are characterized in part by a loss of a specific subtype of neuron in a specific location. It is therefore possible to consider the replacement of these cells to restore the lost function. With the advent of vastly improved cell sources (such as induced pluripotent stem cell derived neurons), it is now time to focus on overcoming the bottleneck in the transplantation process: poor graft survival. Poor cell survival post transplantation continues to be a major barrier to grafting success with survival rates typically less than 10% for fetal tissue and much lower again for stem cells. This DFG funded project (REF: NE2052/2-1) aims to tackle this problem for an entirely new and previously unexplored angle: biomaterial constructs designed to improve cell survival post transplantation. During this project we have found out that although the literature shows there is a drastic lack of oxygen in the graft core (hypoxia), stem cells can actually survive well in these conditions. We hypothesize that this is due to cells reverting to anaerobic respiration pathways. We have instead shown that glucose is a far more critical factor determining cell survival. To date, there are no glucose releasing biomaterial devices, so this project renewal is requesting funding to synthesize and characterize such materials. These would be based around encapsulation of glucose within a biodegradable poly(β-amino ester) network, using a microfluidic flow focusing device to create uniform microspheres capable of being injected through small gauge needles. Upon recommendation by Dr. Burkhard Jahnen, the original proposal (that requested four years of funding), was shortened to two years with a renewal application possible for the remaining two years. The student working on this project has been extremely hard working and productive (already working on a first author manuscript), and we are now requesting funding to add the important aspect described above to his PhD project.