RESUMO
Multipotent adult stem cells capable of developing into particular neuronal cell types have great potential for autologous cell replacement therapy for central nervous system neurodegenerative disorders and traumatic injury. Bone marrow-derived stromal mesenchymal stem cells (BMSCs) appear to be attractive starting materials. One question is whether BMSCs could be coaxed to differentiate in vitro along neuronal or glial lineages that would aid their functional integration post-transplantation, while reducing the risk of malignant transformation. Recent works suggest that BMSCs could indeed be differentiated in vitro to exhibit some cellular and physiological characteristics of neural cell lineages, but it is not likely to be achievable with simple chemical treatments. We discussed recent findings pertaining to efforts in neuronal differentiation of BMSCs in vitro, and results obtained when these were transplanted in vivo.
Assuntos
Células-Tronco Mesenquimais/citologia , Células-Tronco Multipotentes/citologia , Células Estromais/citologia , Animais , Medula Óssea/efeitos dos fármacos , Proteínas de Transporte/genética , Proteínas de Transporte/fisiologia , Diferenciação Celular/efeitos dos fármacos , Linhagem da Célula , Células Cultivadas/citologia , Células Cultivadas/efeitos dos fármacos , Células Cultivadas/transplante , Técnicas de Cocultura , Meios de Cultura , AMP Cíclico/fisiologia , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/efeitos dos fármacos , Camundongos , Células-Tronco Multipotentes/efeitos dos fármacos , Degeneração Neural/cirurgia , Proteínas do Tecido Nervoso/biossíntese , Proteínas do Tecido Nervoso/genética , Neuroglia/citologia , Neurônios/citologia , Ratos , Especificidade da Espécie , Células Estromais/efeitos dos fármacos , TransgenesRESUMO
Protein ubiquitination has critical roles in neuronal physiology and defects in protein ubiquitination have been implicated in neurodegenerative pathology. The anaphase-promoting complex/cyclosome (APC/C) is one of two key E3 ubiquitin ligase complexes that functions in regulating cell cycle transitions in proliferating cells by acting on cyclins and components of the mitotic/meiotic apparatus. Documentation of APC/C's action beyond cell division is sparse. In the past year, however, novel and surprising roles for APC/C in postmitotic neurons, particularly in the modulation of axonal growth and synaptic functions, have been revealed. APC/C and its activator Cdh-1 are found in good abundance in neurons, and these seem to function at different cellular locations, modulating apparently diverse processes such as axonal growth and synaptic function. Interestingly, there also appears to be a single link to these apparently divergent actions of APC/C in neurons--the multi-domain, multi-functional scaffolding protein Liprin-alpha which is an APC/C substrate.
