Advances in stem cell research for parkinson disease

Abstract

There is significant interest in using stem cells as a cell source for treatment against Parkinson's and other diseases due to the limited self-repair ability of the central nervous system and the lack of a pharmacological treatment to replace lost neurons. Parkinson's disease is one of the main neurodegenerative disorders, and it is characterized by the degeneration of the nigrostriatal pathway caused by loss of ventral midbrain dopaminergic neurons in the substantia nigra pars compacta. Currently, there are no treatments to halt disease progress; the treatments merely ameliorate motor symptoms for a time, but the treatments are often followed by severe side effects. Cell-replacement therapy has been proposed as a treatment to replace damaged neurons and protect the remaining cells. Preliminary studies have utilized adult tissues, embryonic/fetal tissues, and embryonic stem cells as a source of dopaminergic cells. However, the ethical issues related to this type of procedure, the high quantity of required cells, the risk of tumor formation, and the immunological rejection associated with it have prevented this technique from being an effective treatment against Parkinson's disease. Researchers have been challenged to focus on new cell-replacement alternatives. In 2006, researchers found that only four transcription factors were necessary to reprogram an adult somatic cell to an induced pluripotent stem cell. This breakthrough revolutionized the scientific community, as this technique would allow scientists to obtain specific cells from the patient, avoiding rejection problems from non-autologous grafts and avoiding ethical problems. In addition, a large number of cells could be obtained. Although induced pluripotent stem (iPS) cells have great potential as a treatment against this disease, there are some obstacles for its clinical use such as the lack of standardized protocols that result in a dopaminergic cell phenotype that grafts without undifferentiated cells and without a risk of tumor formation. Currently, the iPS cell system is an ideal model of study for many other diseases besides Parkinson's, and the system is also good for drug screening. Recently, the direct reprogramming of somatic cells to induce neuronal (iN) cells without generating a pluripotent stage could be the solution to avoiding tumor formation risk. However, as a result of the low quantity of cells obtained, more investigations are necessary to convert this technique into an efficient cell-replacement therapy. If we overcome these obstacles, the use of iPS and iN cells could be, without a doubt, a promising therapy in the near future.