Study of the cytological features of bone marrow mesenchymal stem cells from patients with neuromyelitis optica

Abstract

Neuromyelitis optica (NMO) is a refractory autoimmune inflammatory disease of the central nervous system without an effective cure. Autologous bone marrow-derived mesenchymal stem cells (BM-MSCs) are considered to be promising therapeutic agents for this disease due to their potential regenerative, immune regulatory and neurotrophic effects. However, little is known about the cytological features of BM-MSCs from patients with NMO, which may influence any therapeutic effects. The present study aimed to compare the proliferation, differentiation and senescence of BM-MSCs from patients with NMO with that of age- and sex-matched healthy subjects. It was revealed that there were no significant differences in terms of cell morphology or differentiation capacities in the BM-MSCs from the patients with NMO. However, in comparison with healthy controls, BM-MSCs derived from the Patients with NMO exhibited a decreased proliferation rate, in addition to a decreased expression of several cell cycle-promoting and proliferation-associated genes. Furthermore, the cell death rate increased in BM-MSCs from patients under normal culture conditions and an assessment of the gene expression profile further confirmed that the BM-MSCs from patients with NMO were more vulnerable to senescence. Platelet-derived growth factor (PDGF), as a major mitotic stimulatory factor for MSCs and a potent therapeutic cytokine in demyelinating disease, was able to overcome the decreased proliferation rate and increased senescence defects in BM-MSCs from the patients with NMO. Taken together, the results from the present study have enabled the proposition of the possibility of combining the application of autologous BM-MSCs and PDGF for refractory and severe patients with NMO in order to elicit improved therapeutic effects, or, at the least, to include PDGF as a necessary and standard growth factor in the current in vitro formula for the culture of NMO patient-derived BM-MSCs.