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Biomedical subjects

Christian Andressen

Publications and source records attributed to Christian Andressen.

5 recordsLinked to original sources
PubMed2007

Transplantation of immortalized mesencephalic progenitors (CSM14.1 cells) into the neonatal parkinsonian rat caudate putamen.

The present study analyzed whether grafts of the mesencephalic progenitor cell line CSM14.1 into the neonatal rat caudate putamen (CPu) differentiate into neurons and whether this is accompanied by a functional improvement in 6-hydroxydopamine (6-OHDA)-lesioned animals. As in previous studies, a neuronal differentiation of CSM14.1 cells transplanted into the CPu of adult animals could not be observed, so we here used neonatal rats, because graft location and host age seemingly are crucial parameters for neural transplant differentiation and integration. Rats bilaterally lesioned at postnatal day 1 by intraventricular 6-OHDA-injections 2 days later received 100,000 CSM14.1 cells prelabelled with the fluorescent dye PKH26 into the right CPu. Five weeks after grafting, the cylinder test was performed, and the data compared with data from age-matched intact controls and bilaterally lesioned-only animals. Brain slices immunostained for tyrosine hydroxylase (TH) were quantified by optical densitometry. We observed a significant preference of left forelimb use exclusively in transplanted animals. In these rats, TH-containing perikarya were found in the grafted CPu, presumedly leading to the significant increase of TH-immunoreactive fibers in this region. Moreover, confocal laser microscopy revealed a differentiation of transplanted PKH26-labelled CSM14.1 cells into neuronal nuclei antigen or TH-immunoreactive cells. Thus, CSM14.1 cells differentiate into TH-containing neurons, which most probably contribute to the preferred forelimb use, indicating a functional integration of CSM14.1 cells into the host basal ganglia loops during early postnatal development. These findings that are in contrast to observations in adult rats suggest instructive cues for neuronal differentiation and integration given by the neonatal microenvironment.

Animals↗
PubMed2006

Mesencephalic human neural progenitor cells transplanted into the neonatal hemiparkinsonian rat striatum differentiate into neurons and improve motor behaviour.

Neural stem cell transplantation is a promising strategy for the treatment of neurodegenerative diseases. To evaluate the differentiation potential of human neural progenitor cells (hNPCs) as a prerequisite for clinical trials, we intracerebrally transplanted in vitro expanded fetal mesencephalic hNPCs into hemiparkinsonian rats. On postnatal day one (P1), 17 animals underwent a unilateral intraventricular 6-hydroxydopamine injection into the right lateral ventricle. At P3, animals (n = 10) received about 100,000 hNPCs (1 microL) in the right striatum. Five weeks after birth, animals underwent behaviour tests prior to fixation, followed by immunohistochemistry on brain slices for human nuclei, glial fibrillary acidic protein, S100beta, neuronal nuclei antigen, neuron-specific enolase and tyrosine hydroxylase. Compared with the apomorphine-induced rotations in the lesioned-only group (7.4 +/- 0.5 min(-1)), lesioned and successfully transplanted animals (0.3 +/- 0.1 min(-1)) showed a significant therapeutic improvement. Additionally, in the cylinder test, the lesioned-only animals preferred to use the ipsilateral forepaw. Conversely, the lesioned and transplanted animals showed no significant side bias similar to untreated control animals. Transplanted human nuclei-immunoreactive cells were found to survive and migrate up to 2000 microm into the host parenchyma, many containing the pan-neuronal markers neuronal nuclei antigen and neuron-specific enolase. In the striatum, tyrosine hydroxylase-immunoreactive somata were also found, indicating a dopaminergic differentiation capacity of transplanted hNPCs in vivo. However, the relative number of tyrosine hydroxylase-immunoreactive neurons in vivo seemed to be lower than in corresponding in vitro differentiation. To minimize donor tissue necessary for transplantation, further investigations will aim to enhance dopaminergic differentiation of transplanted cells in vivo.

Animals↗
PubMed2005

The contribution of beta1 integrins to neuronal migration and differentiation depends on extracellular matrix molecules.

The interaction of beta1 integrin receptors and different extracellular matrix molecules during neuronal development was investigated by comparing both migration and morphological differentiation of D3 wild-type embryonic stem (ES) cell line-derived neural precursor cells with those of the beta1 integrin knockout ES cell line G201. Analysing neurosphere explants on laminin and fibronectin as major beta1 integrin ligands, the maximal spreading of outward migrating neuronal cells was determined. Compared with gelatine as a standard substrate, migration was found to be significantly increased for D3-derived neurospheres on fibronectin and laminin-1. These matrix effects were found to be even enhanced for G201 preparations. In addition, also the differentiation of wild-type and beta1 integrin -/- neurones - as determined by MAP-2- and HNK-1-immunoreactive processes - was found to be increased on fibronectin and laminin when compared to gelatine standards. In the respective knockout preparations on these matrices, again perturbation effects were less pronounced than on gelatine. Our observations indicate that laminin and fibronectin are involved both in beta1 integrin-dependent and -independent signalling mechanisms during neurogenesis. Upregulation of compensatory mechanisms such as beta1 integrin-independent receptors for laminin and fibronectin might be responsible for the much less pronounced perturbations of G201 neural precursor migration and differentiation on these two substrates than on gelatine.

Animals↗
PubMed1998

[Microcinematographic studies on neurodifferentiation and neurotoxicity in vitro using mouse embryonic stem cells]

The ontogeny of the mammalian nervous system remains largely unknown, mainly because of the lack of experimental systems that will allow identification of cellular mechanism involved in neuronal maturation. Recently the succesful differentiation of neurons from embryonic stem cells of the BLC-6 cell line has been shown by our group, and these cells are able to form complex neuronal networks with typical electrophysiological characteristica including postsynaptic potentials, comparable to the situation in vivo. Further characterization of neuronal cells revealed characteristic phenotypes, equipped with various neurotransmitters, e.g. glutamate. This excitatory neurotransmitter is reported to be involved in ischemia dependent neurological disorders. As the investigation of toxic effects during neuronal maturation in the embryo is usually rather difficult, due to the limited isolation of early embryonic neurons, the ES cell line seems to be an appropriate model to study effects of neurotoxicological substances. Because of the well known effect of glutamate on dendritic outgrowth and neuronal survival, the in vitro system of embryonic stem cells was applied to study the effect of glutamate intoxication by the receptor agonist NMDA during early neuronal development using videomicroscopic time lapse studies. The results point out that the NMDA induced neurotoxicity correlates with the degree of neuronal differentiation. Despite the existence of NMDA receptors in apolar, bipolar and multipolar neurons, the latter two populations were affected more dramatically than undifferentiated apolar neurons.

Journal Article↗