Toward the treatments with neural stem cells: experiences from amyotrophic lateral sclerosis.
Common pathological features of neurodegenerative diseases are progressive dysfunction and neuronal death. In amyotrophic lateral sclerosis (ALS), motor neurons are selectively affected, leading to death because of paralysis. The main therapeutic goal in neurodegenerative diseases is to diminish neural dysfunction and to replace non-functional cells with the new ones. "Cell-oriented" treatment strategies include isolation of neural stem cells (NSC), their controlled differentiation, and cellular injections targeting the affected region. Beneficial effects of injected cells result from the combination of cell replacement and secretion of the growth factors. Here, we summarize the current state of isolation and differentiation of NSC, and emphasize the embryo tail bud as a particular region where neuroepithelium differentiates from undifferentiated mesenchymal cells over the course of normal development. The possibility to obtain cells from autologous mesenchyme capable of integrating into affected regions represents a major challenge whose achievement should circumvent the pitfall of the immune reaction against transplanted cells. We also present our own results: when intravenously injected in symptomatic ALS rats, NSC migrated to the motor cortex and continued to differentiate. Thus, we illustrate that the use of NSC in rodent models of ALS may represent a paradigm for other neurodegenerative diseases.
Mitrecić
Dinko
D
Laboratoire d'histologie générale, de neuroanatomie et de neuropathologie, Faculté de Médecine, Université Libre de Bruxelles, Route de Lennik 808, Brussels, Belgium. dinko.mitrecic@ulb.ac.be
Gajović
Srećko
S
Pochet
Roland
R
D000690:Amyotrophic Lateral Sclerosis / Q000628:therapy*; D000818:Animals; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000502:physiology; D002469:Cell Separation / Q000379:methods; D006085:Graft Survival / Q000276:immunology; D006801:Humans; D008648:Mesoderm / Q000166:cytology / Q000502:physiology / Q000637:transplantation; D055495:Neurogenesis / Q000502:physiology; D051381:Rats; D033581:Stem Cell Transplantation / Q000379:methods* / Q000639:trends; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*; D014182:Transplantation, Autologous / Q000379:methods