title: Biological Behavior of Human Nucleus Pulposus Mesenchymal Stem Cells in Response to Changes in the Acidic Environment During Intervertebral Disc Degeneration.
abstract: An acidic environment is vital for the maintenance of cellular activities but can be affected tremendously during intervertebral disc degeneration (IVDD). The effect of changes in the acidity of the environment on human nucleus pulposus mesenchymal stem cells (NP-MSCs) is, however, unknown. Thus, this study aimed to observe the biological effects of acidic conditions mimicking a degenerated intervertebral disc on NP-MSCs in vitro. NP-MSCs were isolated from patients with lumbar disc herniation and were further identified by their immunophenotypes and multilineage differentiation. Then, cells were cultured at acidic pH levels (pH 6.2, pH 6.5, pH 6.8, pH 7.1, and pH 7.4) with/without amiloride, an acid-sensing ion channel (ASIC) blocker. The proliferation and apoptosis of NP-MSCs and the expression of stem cell-related genes (Oct4, Nanog, Jagged, Notch1), ASICs, and functional genes (Aggrecan, SOX-9, Collagen-I, and Collagen-II) in NP-MSCs were evaluated. Our work showed that cells obtained from human degenerated NP met the criteria of International Society for Cellular Therapy. Therefore, cells obtained from a degenerated nucleus pulposus were definitively identified as NP-MSCs. Our results also indicated that acidic conditions could significantly inhibit cell proliferation and increase cell apoptosis. Gene expression results demonstrated that acidic conditions could decrease the expression of stem cell-related genes and inhibit extracellular matrix synthesis, whereas it could increase the expression of ASICs. Our study further verified that the above-mentioned biological activities of NP-MSCs could be significantly improved by amiloride. Therefore, the results of the study indicated that the biological behavior of NP-MSCs could be inhibited by acidic conditions during IVDD, and amiloride may meliorate IVDD by improving the activities of NP-MSCs.
authors.affiliation: 1 Department of Spine Surgery, The First Affiliated Hospital of Anhui Medical University , Hefei, People's Republic of China .
authors.forename: Jianjun
authors.initials: J
authors.lastname: Liu
authors.affiliation: 1 Department of Spine Surgery, The First Affiliated Hospital of Anhui Medical University , Hefei, People's Republic of China .
authors.forename: Hui
authors.initials: H
authors.lastname: Tao
authors.affiliation: 1 Department of Spine Surgery, The First Affiliated Hospital of Anhui Medical University , Hefei, People's Republic of China .
authors.forename: Hanbang
authors.initials: H
authors.lastname: Wang
authors.affiliation: 1 Department of Spine Surgery, The First Affiliated Hospital of Anhui Medical University , Hefei, People's Republic of China .
authors.forename: Fulong
authors.initials: F
authors.lastname: Dong
authors.affiliation: 1 Department of Spine Surgery, The First Affiliated Hospital of Anhui Medical University , Hefei, People's Republic of China .
authors.forename: Renjie
authors.initials: R
authors.lastname: Zhang
authors.affiliation: 2 Department of Clinical Laboratory, The First Affiliated Hospital of Anhui Medical University , Hefei, People's Republic of China .
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.affiliation: 1 Department of Spine Surgery, The First Affiliated Hospital of Anhui Medical University , Hefei, People's Republic of China .
authors.forename: Peng
authors.initials: P
authors.lastname: Ge
authors.affiliation: 1 Department of Spine Surgery, The First Affiliated Hospital of Anhui Medical University , Hefei, People's Republic of China .
authors.forename: Peiwen
authors.initials: P
authors.lastname: Song
authors.affiliation: 1 Department of Spine Surgery, The First Affiliated Hospital of Anhui Medical University , Hefei, People's Republic of China .
authors.forename: Huaqing
authors.initials: H
authors.lastname: Zhang
authors.affiliation: 1 Department of Spine Surgery, The First Affiliated Hospital of Anhui Medical University , Hefei, People's Republic of China .
authors.forename: Peng
authors.initials: P
authors.lastname: Xu
authors.affiliation: 3 Biology Department, School of Life Science, Anhui Medical University , Hefei, People's Republic of China .
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Liu
authors.affiliation: 1 Department of Spine Surgery, The First Affiliated Hospital of Anhui Medical University , Hefei, People's Republic of China .
authors.forename: Cailiang
authors.initials: C
authors.lastname: Shen
mesh_terms: D000328:Adult; D000943:Antigens, Differentiation / Q000096:biosynthesis*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007403:Intervertebral Disc / Q000378:metabolism* / Q000473:pathology; D055959:Intervertebral Disc Degeneration / Q000378:metabolism* / Q000473:pathology; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged
chemical_list: D000943:Antigens, Differentiation
keywords: NP-MSCs; acidic environment; biological behavior; intervertebral disc