The Human Gastrointestinal Tract, a Potential Autologous Neural Stem Cell Source

Stem cell therapies seem to be an appropriate tool for the treatment of a variety of diseases, especially when a substantial cell loss leads to a severe clinical impact. This is the case in most neuronal cell losses. Unfortunately, adequate neural stem cell sources are hard to find and current alternatives, such as induced programmed stem cells, still have incalculable risks. Evidence of neurogenesis in the adult human enteric nervous system brought up a new perspective. In humans the appendix harbors enteric neuronal tissue and is an ideal location where the presence of neural stem cells is combined with a minimal invasive accessibility. In this study appendices from adults and children were investigated concerning their neural stem cell potential. From each appendix tissue samples were collected, and processed for immunohistochemistry or enteric neural progenitor cell generation. Free-floating enteric neurospheres (EnNS’s) could be generated after 6 days in vitro. EnNS’s were either used for transplantation into rat brain slices or differentiation experiments. Both transplanted spheres and control cultures developed an intricate network with glia, neurons and interconnecting fibers, as seen in primary enteric cultures before. Neuronal, glial and neural stem cell markers could be identified both in vitro and in vivo by immunostaining. The study underlines the potential of the enteric nervous system as an autologous neural stem cell source. Using the appendix as a potential target opens up a new perspective that might lead to a relatively unproblematic harvest of neural stem cells.

干细胞疗法似乎是治疗多种疾病的适宜手段，尤其当大量细胞丢失引发严重临床影响时，此类情况在多数神经元细胞丢失病症中均有发生。遗憾的是，合适的神经干细胞（neural stem cell）来源极难获取，当前的替代方案（如诱导性编程干细胞）仍存在难以估量的风险。成人肠神经系统（enteric nervous system）中存在神经发生的相关证据，为该领域带来了全新视角。在人体中，阑尾携带着肠神经组织，是神经干细胞存在与微创获取兼备的理想位点。本研究针对成人与儿童的阑尾，探究了其神经干细胞潜能。研究人员从每一例阑尾样本中采集组织，分别进行免疫组织化学（immunohistochemistry）处理或肠神经祖细胞（enteric neural progenitor cell）培养。体外培养6天后，可获得悬浮肠神经球（free-floating enteric neurospheres，简称EnNS）。这些肠神经球既可被用于移植至大鼠脑片的实验，也可用于分化实验。正如此前原代肠培养的观察结果，移植的神经球与对照培养物均形成了包含神经胶质细胞、神经元及连接纤维的复杂网络。通过免疫染色（immunostaining）可在体外与体内环境中，检测到神经元、神经胶质细胞及神经干细胞标志物。本研究证实了肠神经系统作为自体神经干细胞来源（autologous neural stem cell source）的潜力。以阑尾作为潜在靶点为该领域开辟了全新视角，有望实现相对简便且安全的神经干细胞获取。