Biomedical subjects

Jitka Ourednik

Publications and source records attributed to Jitka Ourednik.

8 recordsLinked to original sources

PubMed2005

The miniature pig as an animal model in biomedical research.

Crucial prerequisites for the development of safe preclinical protocols in biomedical research are suitable animal models that would allow for human-related validation of valuable research information gathered from experimentation with lower mammals. In this sense, the miniature pig, sharing many physiological similarities with humans, offers several breeding and handling advantages (when compared to non-human primates), making it an optimal species for preclinical experimentation. The present review offers several examples taken from current research in the hope of convincing the reader that the porcine animal model has gained massively in importance in biomedical research during the last few years. The adduced examples are taken from the following fields of investigation: (a) the physiology of reproduction, where pig oocytes are being used to study chromosomal abnormalities (aneuploidy) in the adult human oocyte; (b) the generation of suitable organs for xenotransplantation using transgene expression in pig tissues; (c) the skin physiology and the treatment of skin defects using cell therapy-based approaches that take advantage of similarities between pig and human epidermis; and (d) neurotransplantation using porcine neural stem cells grafted into inbred miniature pigs as an alternative model to non-human primates xenografted with human cells.

Aneuploidy↗

PubMed2005

Graft/host relationships in the developing and regenerating CNS of mammals.

A new light was shed on the utility of neural grafts when it was recognized that donor tissues and cells offer more than a source of immature progenitors potentially capable of cell replacement: First, they have the inherent capacity to produce multiple trophic and tropic factors promoting cell survival and tissue plasticity often characteristic of the immature central nervous system (CNS). Second, by their interaction with the host microenvironment via cell/cell and cell/ECM interactions, these grafts are capable of re-establishing homeostasis, which can be, for example, reflected in rescue and protection of host elements from harmful influences. This second capacity of donor cells relies, in part, also on a "dormant" but still present regenerative capacity of mature or even aged CNS and on the possibility of its mobilization in the damaged nervous system by neural grafts. For this to occur efficiently after transplantation, a bi-directional dialogue between donor and host cells must gradually be established, in which both "partners" transmit signals (cell/cell contact, molecular messengers), "listen to" and "understand" each other and are able to react by modifying their own plasticity- and development-related programs. Thus, for the best possible recovery of functionality in the injured adult and aged nervous system, neurotransplantation must always try to find optimal conditions for all three of the mentioned qualities of neural grafts, especially for the protection and/or reactivation of neural circuitry embedded in non-neurogenic CNS areas. Once fully understood, this newly recognized aspect of neurotransplantation (and topic of this review) might, someday, even allow the recovery of systems that would otherwise be doomed, such as cognition- and experience-related circuitry.

Animals↗

PubMed2005

Grafted neural stem cells shield the host environment from oxidative stress.

Here, we present our preliminary data showing that neural stem cells (NSCs) can prevent the degeneration of striatal neurons when transplanted into the CNS prior to intoxication with 3-nitropropionic acid (3-NP). In the adult CNS, the number of NSCs, a major source of neural cell populations and plasticity-modulating factors, is relatively low if compared to that of the developing brain. This, together with the adult growth-inhibitory environment, limits its regenerative capacity. Our recent observation has shown that grafted NSCs may rescue/protect neurons in the chronically impaired mesostriatal system. On the basis of this study and because we were also intrigued by our recent observations regarding the rescue/protective role of NSCs in vitro, we decided to test the hypothesis that grafted NSCs can also be deposited preventively in the CNS (and perhaps join the pool of endogenous NSCs of the intact host brain) for later buffering and maintenance of homeostasis when the host is exposed to oxidative stress.

Animals↗

PubMed2004

Stem cells: cross-talk and developmental programs.

The thesis advanced in this essay is that stem cells-particularly those in the nervous system-are components in a series of inborn 'programs' that not only ensure normal development, but persist throughout life so as to maintain homeostasis in the face of perturbations-both small and great. These programs encode what has come to be called 'plasticity'. The stem cell is one of the repositories of this plasticity. This review examines the evidence that interaction between the neural stem cell (as a prototypical somatic stem cell) and the developing or injured brain is a dynamic, complex, ongoing reciprocal set of interactions where both entities are constantly in flux. We suggest that this interaction can be viewed almost from a 'systems biology' vantage point. We further advance the notion that clones of exogenous stem cells in transplantation paradigms may not only be viewed for their therapeutic potential, but also as biological tools for 'interrogating' the normal or abnormal central nervous system environment, indicating what salient cues (among the many present) are actually guiding the expression of these 'programs'; in other words, using the stem cell as a 'reporter cell'. Based on this type of analysis, we suggest some of the relevant molecular pathways responsible for this 'cross-talk' which, in turn, lead to proliferation, migration, cell genesis, trophic support, protection, guidance, detoxification, rescue, etc. This type of developmental insight, we propose, is required for the development of therapeutic strategies for neurodegenerative disease and other nervous system afflictions in humans. Understanding the relevant molecular pathways of stem cell repair phenotype should be a priority, in our view, for the entire stem cell field.

Brain↗

PubMed2004

Multifaceted dialogue between graft and host in neurotransplantation.

Current restorative neurotransplantation research focuses mainly on the potential of the neural graft to replace damaged or missing cell populations and to deliver needed gene products in the form of transgenes. Because of this graft-oriented bias of the procedure, possible dormant regenerative capabilities within the host have been largely underestimated and dismissed as insignificant. This review discusses existing evidence that neural grafts can have stimulating effects on host-intrinsic plasticity that can help regeneration of the mammalian central nervous system. If confirmed, the synergistic interaction between graft and host might substantially enhance our therapeutic possibilities.

Animals↗

PubMed2004

Graft-induced plasticity in the mammalian host CNS.

In this review we trace back the history of an idea that takes a new approach in restorative neurotransplantation by focusing on the "multifaceted dialogue" between graft and host and assigns a central role to graft-evoked host plasticity. In several experimental examples ranging from the transfer of solid fetal tissue grafts into mechanical cortical injuries to deposits of neural stem cells into hemisectioned spinal cord. MPTP-damaged substantia nigra or mutant cerebella supportive evidence is provided for the hypothesis, that in many CNS disorders regeneration of the host CNS can be achieved by taking advantage of the inherent capacity of neural grafts to induce protective and restorative mechanisms within the host. This principle might once allow us to spare even complex circuitry from neurodegeneration.

Animals↗

PubMed2002

Neural stem cells display an inherent mechanism for rescuing dysfunctional neurons.

We investigated the hypothesis that neural stem cells (NSCs) possess an intrinsic capacity to "rescue" dysfunctional neurons in the brains of aged mice. The study focused on a neuronal cell type with stereotypical projections that is commonly compromised in the aged brain-the dopaminergic (DA) neuron. Unilateral implantation of murine NSCs into the midbrains of aged mice, in which the presence of stably impaired but nonapoptotic DA neurons was increased by treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), was associated with bilateral reconstitution of the mesostriatal system. Functional assays paralleled the spatiotemporal recovery of tyrosine hydroxylase (TH) and dopamine transporter (DAT) activity, which, in turn, mirrored the spatiotemporal distribution of donor-derived cells. Although spontaneous conversion of donor NSCs to TH(+) cells contributed to nigral reconstitution in DA-depleted areas, the majority of DA neurons in the mesostriatal system were "rescued" host cells. Undifferentiated donor progenitors spontaneously expressing neuroprotective substances provided a plausible molecular basis for this finding. These observations suggest that host structures may benefit not only from NSC-derived replacement of lost neurons but also from the "chaperone" effect of some NSC-derived progeny.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed2002

Functional recovery following traumatic spinal cord injury mediated by a unique polymer scaffold seeded with neural stem cells.

To better direct repair following spinal cord injury (SCI), we designed an implant modeled after the intact spinal cord consisting of a multicomponent polymer scaffold seeded with neural stem cells. Implantation of the scaffold-neural stem cells unit into an adult rat hemisection model of SCI promoted long-term improvement in function (persistent for 1 year in some animals) relative to a lesion-control group. At 70 days postinjury, animals implanted with scaffold-plus-cells exhibited coordinated, weight-bearing hindlimb stepping. Histology and immunocytochemical analysis suggested that this recovery might be attributable partly to a reduction in tissue loss from secondary injury processes as well as in diminished glial scarring. Tract tracing demonstrated corticospinal tract fibers passing through the injury epicenter to the caudal cord, a phenomenon not present in untreated groups. Together with evidence of enhanced local GAP-43 expression not seen in controls, these findings suggest a possible regeneration component. These results may suggest a new approach to SCI and, more broadly, may serve as a prototype for multidisciplinary strategies against complex neurological problems.

Animals↗