Stem Cells for Neurodegenerative Disorders

Abstract

The use of stem cells in cell replacement therapy for neurodegenerative diseases has received a great deal of scientific and public interest in recent years. This is due to the remarkable pace at which paradigm-changing discoveries have been made regarding the neurogenic potential of embryonic, fetal, and adult cells. Over the last decade, clinical fetal tissue transplants have demonstrated that dopaminergic neurons can survive long term and provide functional clinical benefits for patients with Parkinson's disease. Pluripotent embryonic stem cells and multipotent neural stem cells may provide renewable sources that could replace these primary fetal grafts. Considerable advancement has been made in generating cultures with high numbers of neurons in general and of dopaminergic neurons using a varied array of techniques. However, much of this encouraging progress still remains to be tested on long-term expanded human cultures. Further problems include the low survival rate of these cells following transplantation and the tumorigenic tendencies of embryo-derived cells. However, pre-differentiation or genetic modification of stem cell cultures prior to transplantation may help lead to the generation of high numbers of cells of the desired phenotype following grafting. Boosting particular factors or substrates in the culture media may also protect grafted neurons from oxidative and metabolic stress, and provide epigenetic trophic support. Possible endogenous sources of cells for brain repair include the transdifferentiation of various types of adult cells into neurons. Despite the excitement generated by examples of this phenomenon, further work is needed in order to identify the precise instructive cues that generate neural cells from many other tissue types, and whether or not the new cells are functionally normal. Furthermore, issues such as cell homogeneity and fusion need to be addressed further before the true potential of transdifferentiation can be known. Endogenous stem cells also reside in the neurogenic zones of the adult brain (ventricle lining and hippocampus). Further elucidation of the mechanisms that stimulate cell division and migration are required in order to learn how to amplify the small amount of new cells generated by the adult brain and to direct these cells to areas of injury or degeneration. Finally, a more fundamental understanding of brain injury and disease is required in order to circumvent local brain environmental restrictions on endogenous cell differentiation and survival.

Therapeutic effects of human amniotic epithelial cell transplantation on double-transgenic mice co-expressing APPswe and PS1ΔE9-deleted genes

“…Recent studies using implanted cells, including adult stem cells and fetal transplants, provide promising results in experimental models of neurodegenerative disease, such as Alzheimer's disease [17,18]. HAECs express surface markers typically present on embryonic stem and germ cells.…”

Antagonism of Sphingosine 1-Phosphate Receptor-2 Enhances Migration of Neural Progenitor Cells Toward an Area of Brain Infarction

“…3,4 Identifying candidate molecules that could play a role in NPC migration is crucial for understanding proper tissue formation by newly formed neural cells, as well as for developing novel therapies to promote neural repair after CNS injury. 18,19 We previously showed a role for S1P in NPC migration toward a pathologic area of the CNS and proposed that elevation of S1P at the site of injury was a guiding factor for NPC migration. 6 Here, we reveal that S1P 2 R is a potential target for strategies aiming to increase NPC migration after brain ischemia.…”

Rescue of radiation-induced cognitive impairment through cranial transplantation of human embryonic stem cells

“…Bone marrow-derived stem cells that are capable of reconstituting the immune system after irradiation (27), have also been found to facilitate the repair of brain injury in rodent models (28). A number of stem and progenitor cell types have been proposed for the treatment of neurological diseases including neural, bone marrow, umbilical cord, and embryonic stem cells (29,30). Many of these approaches have been used successfully in animal models to ameliorate degenerative conditions such as Alzheimer's (31, 32), Parkinson's (33,34), and Huntington's (35) disease, as well as other disorders such as epilepsy (36)(37)(38), excitotoxic brain damage (39), and traumatic brain injury (40).…”