Bioprocessing strategies to enhance the challenging isolation of neuro-regenerative cells from olfactory mucosa

Olfactory ensheathing cells (OECs) are a promising potential cell therapy to aid regeneration. However, there are significant challenges in isolating and characterizing them. In the current study, we have explored methods to enhance the recovery of cells expressing OEC marker p75NTR from rat mucosa. With the addition of a 24-hour differential adhesion step, the expression of p75NTR was significantly increased to 73 ± 5% and 46 ± 18% on PDL and laminin matrices respectively. Additionally, the introduction of neurotrophic factor NT-3 and the decrease in serum concentration to 2% FBS resulted in enrichment of OECs, with p75NTR at nearly 100% (100 ± 0% and 98 ± 2% on PDL and laminin respectively), and candidate fibroblast marker Thy1.1 decreased to zero. Culturing OECs at physiologically relevant oxygen tension (2–8%) had a negative impact on p75NTR expression and overall cell survival. Regarding cell potency, co-culture of OECs with NG108-15 neurons resulted in more neuronal growth and potential migration at atmospheric oxygen. Moreover, OECs behaved similarly to a Schwann cell line positive control. In conclusion, this work identified key bioprocessing fundamentals that will underpin future development of OEC-based cell therapies for potential use in spinal cord injury repair. However, there is still much work to do to create optimized isolation methods

MPTP: advances from an evergreen neurotoxin

Since its discovery in 1976, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) models in rodents and nonhuman primates have continuously renewed to keep up with progresses of Parkinson’s disease (PD) research. MPTP is able to reproduce almost all the clinical and neuropathological features of PD when administered to monkeys. In contrast, up to date no rodent model has been able to reproduce all PD features in one. Nevertheless, MPTP is a very versatile neurotoxin that can reproduce different aspects of PD pathology, depending upon the dose and regimen of administration. At the present time, a number of different MPTP models have been developed, allowing researchers to investigate either the classical PD neuropathology and neuroprotective mechanisms or known pathological processes underlining more recently discovered aspects of the disease, such as nonmotor symptoms. In this chapter primate and rodent MPTP models are reviewed, focusing mainly on the contribution that different MPTP protocols can offer to reproduce the multifaceted aspects of the disease