Diversity of Ion Channels in Human Bone Marrow Mesenchymal Stem Cells from Amyotrophic Lateral Sclerosis Patients

  • Park, Kyoung-Sun (Division of Molecular and Life Sciences, Hanyang University) ;
  • Choi, Mi-Ran (Division of Molecular and Life Sciences, Hanyang University) ;
  • Jung, Kyoung-Hwa (Division of Molecular and Life Sciences, Hanyang University) ;
  • Kim, Seung-Hyun (Department of Neurology, Hanyang University Hospital) ;
  • Kim, Hyun-Young (Department of Neurology, Hanyang University Hospital) ;
  • Kim, Kyung-Suk (Bioengineering Institute, CoreStem Inc.) ;
  • Cha, Eun-Jong (Department of Biomedical Engineering, College of Medicine, Chungbuk National University) ;
  • Kim, Yang-Mi (Department of Physiology, College of Medicine, Chungbuk National University) ;
  • Chai, Young-Gyu (Division of Molecular and Life Sciences, Hanyang University)
  • 발행 : 2008.12.31

초록

Human bone marrow mesenchymal stem cells (hBM-MSCs) represent a potentially valuable cell type for clinical therapeutic applications. The present study was designed to evaluate the effect of long-term culturing (up to $10^{th}$ passages) of hBM-MSCs from eight individual amyotrophic lateral sclerosis (ALS) patients, focusing on functional ion channels. All hBM-MSCs contain several MSCs markers with no significant differences, whereas the distribution of functional ion channels was shown to be different between cells. Four types of $K^+$ currents, including noise-like $Ca^{+2}$-activated $K^+$ current ($IK_{Ca}$), a transient outward $K^+$ current ($I_{to}$), a delayed rectifier $K^+$ current ($IK_{DR}$), and an inward-rectifier $K^+$ current ($K_{ir}$) were heterogeneously present in these cells, and a TTX-sensitive $Na^+$ current ($I_{Na,TTX}$) was also recorded. In the RT-PCR analysis, Kv1.1,, heag1, Kv4.2, Kir2.1, MaxiK, and hNE-Na were detected. In particular, ($I_{Na,TTX}$) showed a significant passage-dependent increase. This is the first report showing that functional ion channel profiling depend on the cellular passage of hBM-MSCs.

키워드

참고문헌

  1. Balana B, Nicoletti C, Zahanich I, Graf EM, Christ T, Boxberger S, Ravens U. 5-Azacytidine induces changes in electrophysiological properties of human mesenchymal stem cells. Cell Res 16: 949-960, 2006 https://doi.org/10.1038/sj.cr.7310116
  2. Banfi A, Muraglia A, Dozin B, Mastrogiacomo M, Cancedda R, Quarto R. Proliferation kinetics and differentiation potential of ex vivo expanded human bone marrow stromal cells: Implications for their use in cell therapy. Exp Hematol 28: 707-715, 2000 https://doi.org/10.1016/S0301-472X(00)00160-0
  3. Baxter MA, Wynn RF, Jowitt SN, Wraith JE, Fairbairn LJ, Bellantuono I. Study of telomere length reveals rapid aging of human marrow stromal cells following in vitro expansion. Stem Cells 22: 675-682, 2004 https://doi.org/10.1634/stemcells.22-5-675
  4. Biagiotti T, D'Amico M, Marzi I, Di Gennaro P, Arcangeli A, Wanke E, Olivotto M. Cell renewing in neuroblastoma: electrophysiological and immunocytochemical characterization of stem cells and derivatives. Stem Cells 24: 443-453, 2006 https://doi.org/10.1634/stemcells.2004-0264
  5. Bonab MM, Alimoghaddam K, Talebian F, Ghaffari SH, Ghavamzadeh A, Nikbin B. Aging of mesenchymal stem cell in vitro. BMC Cell Biol 7: 14, 2006 https://doi.org/10.1186/1471-2121-7-14
  6. Deng XL, Lau CP, Lai K, Cheung KF, Lau GK, Li GR. Cell cycle-dependent expression of potassium channels and cell proliferation in rat mesenchymal stem cells from bone marrow. Cell Prolif 40: 656-670, 2007 https://doi.org/10.1111/j.1365-2184.2007.00458.x
  7. Deng XL, Sun HY, Lau CP, Li GR. Properties of ion channels in rabbit mesenchymal stem cells from bone marrow. Biochem Biophys Res Commun 348: 301-309, 2006 https://doi.org/10.1016/j.bbrc.2006.07.054
  8. Friedenstein AJ, Deriglasova UF, Kulagina NN, Panasuk AF, Rudakowa SF, Luria EA, Ruadkow IA. Precursors for fibroblasts in different populations of hematopoietic cells as detected by the in vitro colony assay method. Exp Hematol 2: 83-92, 1974
  9. Hannouche D, Terai H, Fuchs JR, Terada S, Zand S, Nasseri BA, Petite H, Sedel L, Vacanti JP. Engineering of implantable cartilaginous structures from bone marrow-derived mesenchymal stem cells. Tissue Eng 13: 87-99, 2007 https://doi.org/10.1089/ten.2006.0067
  10. Karnieli O, Izhar-Prato Y, Bulvik S, Efrat S. Generation of insulin-producing cells from human bone marrow mesenchymal stem cells by genetic manipulation. Stem Cells 25: 2837-2844, 2007 https://doi.org/10.1634/stemcells.2007-0164
  11. Li GR, Deng XL, Sun H, Chung SS, Tse HF, Lau CP. Ion channels in mesenchymal stem cells from rat bone marrow. Stem Cells 24: 1519-1528, 2006 https://doi.org/10.1634/stemcells.2005-0307
  12. Li GR, Sun H, Deng X, Lau CP. Characterization of ionic currents in human mesenchymal stem cells from bone marrow. Stem Cells 23: 371-382, 2005 https://doi.org/10.1634/stemcells.2004-0213
  13. MacFarlane SN, Sontheimer H. Changes in ion channel expression accompany cell cycle progression of spinal cord astrocytes. Glia 30: 39-48, 2000 https://doi.org/10.1002/(SICI)1098-1136(200003)30:1<39::AID-GLIA5>3.0.CO;2-S
  14. Mazzini L, Mareschi K, Ferrero I, Vassallo E, Oliveri G, Boccaletti R, Testa L, Livigni S, Fagioli F. Autologous mesenchymal stem cells: clinical applications in amyotrophic lateral sclerosis. Neurol Res 28: 523-526, 2006 https://doi.org/10.1179/016164106X116791
  15. Orlic D, Kajstura J, Chimenti S, Jakoniuk I, Anderson SM, Li B, Pickel J, McKay R, Nadal-Ginard B, Bodine DM, Leri A, Anversa P. Bone marrow cells regenerate infarcted myocardium. Nature 410: 701-705, 2001 https://doi.org/10.1038/35070587
  16. Ouadid-Ahidouch H, Roudbaraki M, Delcourt P, Ahidouch A, Joury N, Prevarskaya N. Functional and molecular identification of intermediate-conductance Ca2+-activated K+ channels in breast cancer cells: association with cell cycle progression. Am J Physiol Cell Physiol 287: C125-134, 2004 https://doi.org/10.1152/ajpcell.00488.2003
  17. Park KS, Jung KH, Kim SH, Kim KS, Choi MR, Kim Y, Chai YG. Functional expression of ion channels in mesenchymal stem cells derived from umbilical cord vein. Stem Cells 25: 2044-2052, 2007 https://doi.org/10.1634/stemcells.2006-0735
  18. Rombouts WJ, Ploemacher RE. Primary murine MSC show highly efficient homing to the bone marrow but lose homing ability following culture. Leukemia 17: 160-170, 2003 https://doi.org/10.1038/sj.leu.2402763
  19. Stenderup K, Justesen J, Clausen C, Kassem M. Aging is associated with decreased maximal life span and accelerated senescence of bone marrow stromal cells. Bone 33: 919-926, 2003 https://doi.org/10.1016/j.bone.2003.07.005
  20. Tao R, Lau CP, Tse HF, Li GR. Functional ion channels in mouse bone marrow mesenchymal stem cells. Am J Physiol Cell Physiol 293: C1561-1567, 2007 https://doi.org/10.1152/ajpcell.00240.2007
  21. Tomita S, Li RK, Weisel RD, Mickle DA, Kim EJ, Sakai T, Jia ZQ. Autologous transplantation of bone marrow cells improves damaged heart function. Circulation 100 Suppl 19: II247-256, 1999
  22. Weiss ML, Medicetty S, Bledsoe AR, Rachakatla RS, Choi M, Merchav S, Luo Y, Rao MS, Velagaleti G, Troyer D. Human umbilical cord matrix stem cells: preliminary characterization and effect of transplantation in a rodent model of Parkinson's disease. Stem Cells 24: 781-792, 2006 https://doi.org/10.1634/stemcells.2005-0330