Analysis of olfactory stem- and ensheathing-cells as well as mesenchymal stem cells in contact with cerebrospinal fluid: prerequisite for human cell therapeutic approaches after spinal cord trauma

Status:

completed 02/2021

Aims:

Traumatic spinal cord injuries not only result in physical impairment for affected patients but also present them and their families with social and economic challenges. Therefore, it is so important to analyze potential therapeutic approaches in more detail. In recent years, many preclinical but also some clinical studies have been started.

Activities/Methods:

Besides medication therapies, regenerative cell therapies represent promising approaches, since most patients are in the chronic phase of injury, where neurons and glial cells have died due to a series of secondary inflammatory processes and the formed glial scar represents a physical and a chemical barrier for regeneration. Among the different cell types, autologous stem cells from bone marrow and, in particular, olfactory stem cells from the nasal mucosa, which can be easily obtained by biopsy, represent an attractive cell source. When the stem cells are transplanted into the spinal cord of a patient, they come into contact with cerebrospinal fluid (CSF). Therefore, in the present study the behavior of stem cells in CSF was studied in more detail to exclude possible adverse effects.

Results:

The layers of the olfactory mucosa were separated and the olfactory stem cells from the epithelial layer and the lamina propria were isolated and cultured using the neurosphere assay. Their behavior in CSF was then analyzed in comparison with bone marrow stem cells. All three cell types were vital in CSF with the addition of proteins in the form of Fetal calf serum (FCS) for up to 21 days. Cell functions such as proliferation and migration were preserved in CSF, and none of the cell types showed unwanted reactions such as spontaneous osteogenic, adipogenic or chondrogenic differentiation. While bone marrow stem cells were able to differentiate into chondrocytes, adipocytes and osteoblasts after appropriate induction, stem cells of the lamina propria showed only osteogenic and neuronal differentiation potential. In particular, the cells of the epithelial layer showed differentiation into neuron-like cells (βIII-tubulin positive), which showed increased formation of dendrites when CSF was added. In conclusion, olfactory mucosa stem cells represent a good and safe source for cell therapy. Nevertheless, it is necessary to further characterize the neuronal differentiated cells and to verify their functionality as well as their behavior in suitable carrier matrices (e.g., plasmaclot).

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