Organotypic cultures as tools for optimizing central nervous system cell therapies

Abstract

Stem cell therapy is a promising treatment for neurological disorders such as cerebral ischemia, Parkinson's disease and Huntington's disease. In recent years, many clinical trials with various cell types have been performed often showing mixed results. Major problems with cell therapies are the limited cell availability and engraftment and the reduced integration of grafted cells into the host tissue. Stem cell-based therapies can provide a limitless source of cells but survival and differentiation remain a drawback. An improved understanding of the behaviour of stem cells and their interaction with the host tissue, upon implantation, is needed to maximize the therapeutic potential of stem cells in neurological disorders. Organotypic cultures made from brain slices from specific brain regions that can be kept in culture for several weeks after injecting molecules or cells represent a remarkable tool to address these issues. This model allows the researcher to monitor/assess the behaviour and responses of both the endogenous as well as the implanted cells and their interaction with the microenvironment leading to cell engraftment. Moreover, organotypic cultures could be useful to partially model the pathological state of a disease in the brain and to study graft-host interactions prior to testing such grafts for pre-clinical applications. Finally, they can be used to test the therapeutic potential of stem cells when combined with scaffolds, or other therapeutic enhancers, among other aspects, needed to develop novel successful therapeutic strategies or improve on existing ones.

An in vitro spinal cord injury model to screen neuroregenerative materials

“…In particular, there is a major current need to develop facile, high throughput in vitro models 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 that: (i) mimic pathological features of injury sites in vivo (and therefore have biological validity); (ii) are compatible with introduction of nano-engineered constructs for the robust and reproducible testing of the latter; and (iii) induce comparable cellular responses to the introduced materials as those in live animal injury models [12].…”

P2Y1 receptor mediated neuronal fibre outgrowth in organotypic brain slice co-cultures

“…They retain the morphological characteristics of the cells and maintain the cytoarchitecture and the microenvironment of the original tissue (Cho et al, 2007;Del Rio and Soriano, 2010;Heine et al, 2013;Stavridis et al, 2009). This threedimensional environment has tremendous value for evaluating the efficacy of compounds, by preserving external mechanical inputs, the interactions between different cell structures like neurons and glial cells and cell adhesion parameters, which all profoundly affect intracellular signalling (for details see Daviaud et al, 2013). Neuron-glia interactions are especially important because purinergic receptors e.g.…”

In Vitro Models of Spinal Cord Injury

“…Thus, OTSs have their own advantages and disadvantages with regard to stimulating in vivo conditions. Obviously, organotypic slices cannot replace in vivo models, which are still necessary and remain the only way to evaluate the functional outcome of a therapeutic strategy [59].…”