Abstract
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.
Highlights
Stroke, cerebrovascular disease and neurodegeneration are major causes of mortality and disability [1]
Nanog is a protein expressed in embryonic stem cells and is together with Sox2 and Oct4 thought to be a key factor in maintaining pluripotency [45,46]
For ß-Tubulin III (Fig. 8F) and Nestin (Fig. 8G) a co-labeling for transplanted and indigene neuronal cells could be demonstrated, similar to the rat cultures. In this presented work we demonstrated the ability to cultivate and differentiate enteric neurospheres (EnNS’s) from human appendix tissue of all ages
Summary
Cerebrovascular disease and neurodegeneration are major causes of mortality and disability [1]. Their common characteristics are a progressive loss of structure and function [2] that cannot be overcome by healing processes. Despite dramatic advancements in medical care, effective clinical therapies are limited and therapeutic strategies that restore neuronal and glial cells as well as functional circuits are lacking. Therapeutic strategies should facilitate endogenous regeneration, attenuate neurotoxic effects and achieve functional improvement. Stem cell transplantation has emerged as a potential therapeutic approach for cell replacement in ischemic brain injuries or neurodegenerative diseases [9,10,11]
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