Neurological diseases afflict a growing proportion of the human population. or

Neurological diseases afflict a growing proportion of the human population. or heal the patient. In the last two decades the transplantation approach by means of stem cells of different origin has been suggested for the treatment of neurological diseases. The choice of slightly different animal models and the differences in Fenoprofen calcium methods of stem cell preparation make it hard to compare the results of transplantation experiments. Moreover the translation of these results into clinical trials with human subjects is hard and has so far met with little success. This review seeks Fenoprofen calcium to discuss the reasons for these troubles by considering the differences between human and animal cells (including isolation handling and transplantation) and between the human disease model and the animal disease model. (Double 2012 For over 30 years the most widely used treatment of PD has Fenoprofen calcium been levodopa (L-DOPA) which is usually converted into dopamine in the dopaminergic neurons by dopa decarboxylase. Since motor symptoms are caused by a deficiency of dopamine in the were able to induce a partial recovery in parkinsonian monkeys (Takagi et al. 2005 and rats (Ferrari et al. 2006 and were able to integrate in the striatum generating Tyrosine Hydroxylase (TH)+ neurons. Also SCI has been treated using the transplantation of ESCs either using differentiated ESCs (such as oligodendrocytes precursors) (Liu et al. 2000 where the cells migrate and differentiate in mature oligodendrocytes capable of myelinating axons or undifferentiated cells (Bottai et al. 2010 where they have mainly a trophic role reducing the inflammation and preserving the myelin of the ventral columns. Retinoic acid pretreated ESCs were also successfully used in ischemic rat models (Wei et al. 2005 where they enhanced functional recovery on neurological and behavioral assessments. Moreover motor neuron differentiated ESCs were able to induce a motor improvement in a genetic rat model of ALS (Lopez-Gonzalez et al. 2009 and multipotent neural precursors (NPs) reduced the clinical indicators of MS in a mouse model of experimental autoimmune encephalomyelitis by means of the attenuation of the inflammatory process (Aharonowiz et al. 2008 Regardless of their potentiality the use of undifferentiated ESCs raises considerable numbers of issues about the formation of tumors and teratomas although such a risk decreases with their progressive cellular differentiation (i.e. reduced multipotency); in addition to these factors we must not forget that there are many ethical issues around ESCs. In 2006 a new frontier was opened up by Yamanaka (Takahashi and Yamanaka 2006 The production of embryonic-like stem cells originating from adult cells (mostly fibroblasts) put an end to the ethical issues around the use of pluripotent stem Prox1 cells. These induced pluripotent stem cells obtained by the introduction of four genes Oct3/4 Sox2 c-Myc and Klf4 which have a transcriptional factor activity in the early phases of their development have physiological and molecular characteristics similar to ES with respect to their proliferation and differentiation potentiality. Moreover iPS induction in mice exhibited that in experimental conditions the iPS have an unexpected capacity to form embryo-like structures including the three germ layers and the extra-embryonic structures indicating that induction can achieve an even earlier stage of development than the ESCs (Abad et al. 2013 The affinity of iPS with the ESCs Fenoprofen calcium makes these cells suitable for a similar application in animal models of neurological pathology. Indeed it has been exhibited that human iPS differentiate into DA progenitor cells and transplanted into a chemically induced PD rat survive long term and develop into DA neurons and integrate into the brain parenchyma. However some cells produced tumour-like nestin positive Fenoprofen calcium cells raising some concern about the security of these cells (Cai et al. 2010 indeed in another study in order to minimize the risk of tumour formation the dopaminergic derived iPS cells were separated from contaminating pluripotent cells by means of fluorescence-activated cell sorting (Wernig et al. 2008 Protein-based iPS differentiated to the terminally-matured DA neurons as the ESCs did but experienced higher levels of DA neuron-specific markers’ expression than ES cells indicating that iPS were a suitable source for PD patient-specific treatment (Kwon et al. 2014.

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