The functional deficiency of bone marrow mesenchymal stromal cells in ALS patients is proportional to disease progression rate

Abstract

Amyotrophic lateral sclerosis (ALS) is caused by motor neuron death. The relationship between the prognosis of ALS patients and the function of their bone marrow mesenchymal stromal cells (BM-MSCs) is unclear. We designed this study to assess the correlation between the progression rate of the ALS Functional Rating Scale-revised version (ΔFS), which is reported to predict prognosis, and the pluripotency and trophic factor secreting capacity of ALS patients' BM-MSCs. We evaluated ΔFS in 23 ALS patients and isolated BM-MSCs from those patients and five healthy people. Levels of Nanog, Oct-4, and Nestin mRNA were examined to evaluate pluripotency, and levels of BDNF, ECGF1, bFGF-2, HGF, IGF-1, PGF, TGF-1β, SDF-1α, GDNF, VEGF, and ANG mRNA were examined to assess trophic factor secreting capacity. In addition, we measured the protein levels of Nanog, Oct-4, Nestin, SDF-1α, ANG, bFGF-2, VEGF, IGF-1, GDNF, and BDNF. mRNA levels of Nanog, Oct-4, ECGF1, bFGF-2, HGF, IGF-1, PGF, TGF-1β, SDF-1α, GDNF, VEGF, and ANG were negatively correlations with ΔFS. However, those of Nestin and BDNF were not significantly correlated with ΔFS. Similarly, Nanog, Oct-4, SDF-1α, ANG, bFGF-2, VEGF, IGF-1, and GDNF protein levels had a significant negative correlation with ΔFS. Results indicate that the pluripotency and trophic factor secreting capacity of the BM-MSCs of ALS patients are reduced in proportion to a poorer prognosis. We therefore suggest that healthy allogeneic BM-MSCs might be a better option for cell therapy in ALS patients.