Neurodegeneration and cell replacement

Ormerod, Brandi K.; Palmer, Theo D.; Caldwell, Maeve A.

doi:10.1098/rstb.2006.2018

Cited by 47 publications

(36 citation statements)

References 173 publications

(252 reference statements)

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“…The discovery of adult neurogenesis has raised hopes that the insights gained into the mechanisms of stem cell activation and the integration of newly formed neurons can be applied for neurorestoration and neuroregeneration in the diseased brain [1,2]. One of the prime targets for cell replacement therapies is Parkinson's disease that is characterised by the greatly reduced activity of dopaminergic neurons primarily of the pars compacta of the substantia nigra.…”

Section: Introductionmentioning

confidence: 99%

Nucleotides affect neurogenesis and dopaminergic differentiation of mouse fetal midbrain-derived neural precursor cells

Delic

Zimmermann

2010

Purinergic Signalling

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The fetal midbrain is a preferred source for isolating and producing dopaminergic neurons for subsequent grafting and replacement of damaged or lost dopaminergic midbrain neurons. We analysed the potential of a variety of nucleotides and of adenosine to support dopaminergic neuron formation from primary mouse fetal midbrain-derived cells, harvested at E10.5 and at E13.5 and subjected to adherent cell culture. In contrast to cells derived at E13.5, cells derived at E10.5 have the potential to produce dopaminergic neurons in culture. These neurons express tyrosine hydroxylase and the dopamine transporter. The fetal ventral midbrain contained mRNA encoding almost all P2X and P2Y receptors, all adenosine receptors as well as the ectonucleotidases nucleoside triphosphate diphosphohydrolase 2 and tissue nonspecific alkaline phosphatase. Essentially, all components of the purinergic signalling pathway were also expressed by the cultured cells. ATP, ADPβS, 2MeSATP, 2ClATP and adenosine increased neuron formation. There was, however, no preference for the formation of dopaminergic neuronswith the exception of 2ClATP that increased the relative contribution of tyrosine hydroxylase-positive neurons. In cells isolated at E13.5 UTP promoted neuron survival but ADPβS and ATPγS essentially eliminated neurons. These data showed that the outcome of nucleotide application was different even though cells isolated at E10.5 and E13.5 expressed very similar receptor mRNA profiles. They suggest that purinergic agonists carry potential for stimulating neurogenesis and enriching the contribution of dopaminergic neurons in vitro. Nucleotide receptor agonists may be of value for contributing to the formation and survival of dopaminergic neurons in vivo.

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Section: Introductionmentioning

confidence: 99%

Nucleotides affect neurogenesis and dopaminergic differentiation of mouse fetal midbrain-derived neural precursor cells

Delic

Zimmermann

2010

Purinergic Signalling

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“…Several factors may have contributed to the prevention of efficient adaptive immune response activation, including BBB protection, antigen-presenting cell paucity and limited lymphatic drainage [88]. However, post-morterm examinations of fetal NSC graft recipients have revealed activated microglia and host immune cell infiltration at the host-graft interface and throughout the graft, suggesting that inflammation may have compromised graft survival and functional outcome [89,90].…”

Section: Immunology Of Intracranial Deliverymentioning

confidence: 99%

Cell-and Gene-based Therapeutic Approaches for Neurological Deficits in Mucopolysaccharidoses

Pan¹

2011

CPB

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Mucopolysaccharidoses (MPS) are a group of lysosomal storage diseases that are resulted from abnormal accumulation of glycosaminoglycans. Among the progressive multi-organ abnormalities often associated with MPS diseases, the deterioration of central nervous system (CNS) is the most challenging manifestations to be tackled, due to the impermeability of the blood-brain-barrier (BBB). Evolved with recent development in stem cell biotechnology and gene therapy, several novel experimental approaches have been investigated in animal models. In this review, we will address different approaches attempting to bypass the BBB for neuropathic MPS treatment using cell-and gene-based therapies. Several neurological findings in CNS pathophysiology emerged with therapeutic investigation will also be discussed.

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“…Finally, successful cell replacement and tissue regeneration is only achieved once new cells integrate into existing cell clusters, tissues and organs. This is particularly challenging for the central nervous system (CNS ), since it is the organ with the largest variety of cell types, in which the majority of cells are post-mitotic and part of elaborate neural circuits underlying complex behaviour (Lindvall and Kokaia 2006 ;Ormerod et al 2008 ;Kim and de Vellis 2009 ;Vishwakarma et al 2014 ).…”

mentioning

confidence: 99%

Stem Cells and Asymmetric Cell Division

Sousa‐Nunes

Hirth

2016

Regenerative Medicine - From Protocol to Patient

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Asymmetric stem cell division is a widespread process used to generate cellular diversity in developing and adult organisms whilst retaining a steady stem cell pool. When dividing asymmetrically, stem cells self-renew and generate a second cell type, which can be either a differentiating progenitor or a postmitotic cell. Studies in model organisms, most notably the nematode worm Caenorhabditis elegans , the fruitfl y Drosophila melanogaster , and the mouse Mus musculus , have identifi ed interrelated mechanisms that regulate asymmetric cell division, from polarity formation and mitotic spindle orientation, to asymmetric segregation of fate determinants and organelles, that impact growth and proliferation. Mechanisms linking extrinsic signals to cellular asymmetry are also beginning to emerge. These cellular processes are mediated by evolutionary conserved molecules, and together equilibrate numbers of progenitor and differentiated cells. Insights into asymmetric division have enhanced our understanding of stem cell biology and of hypo-or hyper-proliferation as a consequence of its disruption, including cancer formation. These insights are of major interest for regenerative medicine, since asymmetrically dividing stem cells provide a powerful source for targeted cell replacement and tissue regeneration.

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Neurodegeneration and cell replacement

Cited by 47 publications

References 173 publications

Nucleotides affect neurogenesis and dopaminergic differentiation of mouse fetal midbrain-derived neural precursor cells

Nucleotides affect neurogenesis and dopaminergic differentiation of mouse fetal midbrain-derived neural precursor cells

Cell-and Gene-based Therapeutic Approaches for Neurological Deficits in Mucopolysaccharidoses

Stem Cells and Asymmetric Cell Division

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