Derivation of neurons for cell therapy

Abstract

Average life expectancy has increased significantly during recent years, which has led to an increase in the frequency of age-related diseases, including neurodegenerative diseases. One of the most promising lines of research in their treatment is cell therapy. The use of patient-specific cells is optimal since it prevents immune response. This review deals with modern approaches to the change of a cell’s fate with a focus on the derivation of neural cells by means of transdifferentiation. Neural cells can be derived by differentiation of embryonic stem cells to neurons. Such cells will be heterologous; moreover, when using pluripotent cell derivatives there is a risk of tumor formation. By means of therapeutic cloning we can obtain autologous embryonic stem cells which can be differentiated into neurons; however, ethical problems are possible. Induced pluripotent stem cells can be used to obtain patient-specific cells, but there is still some risk of tumor formation. Transdifferentiation is a promising technique for derivation of patient-specific neurons from fibroblasts without the pluripotency stage. However, the question arises whether reprogramming fibroblasts to neurons is complete and the obtained neurons are fully functional. Moreover, it will be difficult to use these mature neurons in cell therapy since they are relatively few and transplant badly. Therefore, the optimal strategy for derivation of cell material for the cell therapy of neurodegenerative diseases nowadays is the use of neural stem cells (NSCs). For the derivation of patient-specific neural stem cells, induced pluripotent stem cells or transdifferentiation of fibroblasts or astrocytes can be used. This review deals with the modern data on transdifferentiation of different types of human cells to neurons and neuron progenitors. Generally speaking, the use of patient-specific neural stem cells will allow for the therapy of some neurodegenerative diseases in the future.