title: 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.
authors: Department of Neurology, Hanyang University College of Medicine, Seoul, Republic of Korea.
authors: Seong-Ho
authors: SH
authors: Koh
authors: Wonki
authors: W
authors: Baik
authors: Min Young
authors: MY
authors: Noh
authors: Goang Won
authors: GW
authors: Cho
authors: Hyun Young
authors: HY
authors: Kim
authors: Kyung Suk
authors: KS
authors: Kim
authors: Seung Hyun
authors: SH
authors: Kim
mesh_terms: D000328:Adult; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000473:pathology*; D015703:Antigens, CD / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology* / Q000502:physiology*; D002478:Cells, Cultured; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D007381:Intermediate Filament Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000502:physiology*; D008875:Middle Aged; D000071317:Nanog Homeobox Protein; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D064231:Nestin; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism; D018709:Statistics, Nonparametric
chemical_list: D015703:Antigens, CD; D018398:Homeodomain Proteins; D036341:Intercellular Signaling Peptides and Proteins; D007381:Intermediate Filament Proteins; C486780:NANOG protein, human; C577484:NES protein, human; D000071317:Nanog Homeobox Protein; D009419:Nerve Tissue Proteins; D064231:Nestin; D050814:Octamer Transcription Factor-3