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http://dx.doi.org/10.4110/in.2014.14.1.54

Molecular Characterization of Neurally Differentiated Human Bone Marrow-derived Clonal Mesenchymal Stem Cells  

Yi, TacGhee (Translational Research Center, Inha University School of Medicine)
Lee, Hyun-Joo (Drug Development Program, Department of Medicine, Inha University School of Medicine)
Cho, Yun-Kyoung (HomeoTherapy Co. Ltd.)
Jeon, Myung-Shin (Translational Research Center, Inha University School of Medicine)
Song, Sun U. (Translational Research Center, Inha University School of Medicine)
Publication Information
IMMUNE NETWORK / v.14, no.1, 2014 , pp. 54-65 More about this Journal
Abstract
Bone marrow-derived mesenchymal stem cells (MSCs) are multipotent, with the ability to differentiate into different cell types. Additionally, the immunomodulatory activity of MSCs can downregulate inflammatory responses. The use of MSCs to repair injured tissues and treat inflammation, including in neuroimmune diseases, has been extensively explored. Although MSCs have emerged as a promising resource for the treatment of neuroimmune diseases, attempts to define the molecular properties of MSCs have been limited by the heterogeneity of MSC populations. We recently developed a new method, the subfractionation culturing method, to isolate homogeneous human clonal MSCs (hcMSCs). The hcMSCs were able to differentiate into fat, cartilage, bone, neuroglia, and liver cell types. In this study, to better understand the properties of neurally differentiated MSCs, gene expression in highly homogeneous hcMSCs was analyzed. Neural differentiation of hcMSCs was induced for 14 days. Thereafter, RNA and genomic DNA was isolated and subjected to microarray analysis and DNA methylation array analysis, respectively. We correlated the transcriptome of hcMSCs during neural differentiation with the DNA methylation status. Here, we describe and discuss the gene expression profile of neurally differentiated hcMSCs. These findings will expand our understanding of the molecular properties of MSCs and contribute to the development of cell therapy for neuroimmune diseases.
Keywords
hcMSC; Mesenchymal stem cell; Neural differentiation; Microarray; Methylation; Subfractionation culturing method;
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1 Song, S. U., C. S. Kim, S. P. Yoon, S. K. Kim, M. H. Lee, J. S. Kang, G. S. Choi, S. H. Moon, M. S. Choi, Y. K. Cho, and B. K. Son. 2008. Variations of clonal marrow stem cell lines established from human bone marrow in surface epitopes, differentiation potential, gene expression, and cytokine secretion. Stem Cells Dev. 17: 451-461.   DOI   ScienceOn
2 Tondreau, T., M. Dejeneffe, N. Meuleman, B. Stamatopoulos, A. Delforge, P. Martiat, D. Bron, and L. Lagneaux. 2008. Gene expression pattern of functional neuronal cells derived from human bone marrow mesenchymal stromal cells. BMC Genomics 9: 166-176.   DOI   ScienceOn
3 Shakhbazov, A. V., N. V. Goncharova, S. M. Kosmacheva, N. A. Kartel, and M. P. Potanev. 2009. Plasticity of human msesnchymal stem cell phenotype and expression profile under neurogenic conditions. Cell Technol. Biol. Med. 2: 513-516
4 Tao, X. R., W. L. Li, J. Su, C. X. Jin, X. M. Wang, J. X.Li, J. K. Hu, Z. H. Xiang, J. T. Lau, and Y. P. Hu. 2009. Clonal mesenchymal stem cells derived from human bone marrow can differentiate into hepatocyte-like cells in injured livers of SCID mice. J. Cell. Biochem. 108: 693-704.   DOI   ScienceOn
5 Hofstetter, C. P., E. J. Schwarz, D. Hess, J. Widenfalk, A. El Manira, D. J. Prockop, and L. Olson. 2002. Marrow stromal cells form guiding strands in the injured spinal cord and promote recovery. Proc. Natl. Acad. Sci. USA 99: 2199-2204.   DOI   ScienceOn
6 Woodbury, D., E. J. Schwarz, D. J. Prockop, and I. B. Black. 2000. Adult rat and human bone marrow stromal cells differentiate into neurons. J. Neurosci. Res. 61: 364-370.   DOI   ScienceOn
7 Deng, W., M. Obrocka, I. Fischer, and D. J. Prockop. 2001. In vitro differentiation of human marrow stromal cells into early progenitors of neural cells by conditions that increase intracellular cyclic AMP. Biochem. Biophys. Res. Commun. 282: 148-152.   DOI   ScienceOn
8 Neuhuber, B., G. Gallo, L. Howard, L. Kostura, A. Mackay, and I. Fischer. 2004. Reevaluation of in vitro differentiation protocols for bone marrow stromal cells: disruption of actin cytoskeleton induces rapid morphological changes and mimics neuronal phenotype. J. Neurosci. Res. 77: 192-204.   DOI   ScienceOn
9 Lu, P., A. Blesch, and M. H. Tuszynski. 2004. Induction of bone marrow stromal cells to neurons: differentiation, transdifferentiation, or artifact? J. Neurosci. Res. 77: 174-191.   DOI   ScienceOn
10 Mareschi, K., M. Novara, D. Rustichelli, I. Ferrero, D. Guido, E. Carbone, E. Medico, E. Madon, A. Vercelli, and F. Fagioli. 2006. Neural differentiation of human mesenchymal stem cells: Evidence for expression of neural markers and eag K+ channel types. Exp. Hematol. 34: 1563-1572.   DOI   ScienceOn
11 Yi, T. and S. U. Song. 2012. Immunomodulatory properties of mesenchymal stem cells and their therapeutic applications. Arch. Pharm. Res. 35: 213-221.   DOI
12 Yoo, H. S., T. Yi, Y. K. Cho, W. C. Kim, S. U. Song, and M. S. Jeon. 2013. Mesenchymal stem cell lines isolated by different isolation methods show variations in the regulation of graft-versus-host disease. Immune Netw. 13: 133-140.   DOI
13 Anderson, P., L. Souza-Moreira, M. Morell, M. Caro, F. O'Valle, E. Gonzalez-Rey, and M. Delgado. 2013. Adiposederived mesenchymal stromal cells induce immunomodulatory macrophages which protect from experimental colitis and sepsis. Gut 62: 1131-1141.   DOI   ScienceOn
14 Jung, K. H., S. U. Song, T. Yi, M. S. Jeon, S. W. Hong, H. M. Zheng, H. S. Lee, M. J. Choi, D. H. Lee, and S. S. Hong. 2011. Human bone marrow-derived clonal mesenchymal stem cells inhibit inflammation and reduce acute pancreatitis in rats. Gastroenterology 140: 998-1008.   DOI   ScienceOn
15 Pittenger, M. F., A. M. Mackay, S. C. Beck, R. K. Jaiswal, R. Douglas, J. D. Mosca, M. A. Moorman, D. W. Simonetti, S. Craig, and D. R. Marshak. 1999. Multilineage potential of adult human mesenchymal stem cells. Science 284: 143-147.   DOI   ScienceOn
16 Wang, G., B. A. Bunnell, R. G. Painter, B. C. Quiniones, S. Tom, N. A. Lanson, Jr., J. L. Spees, D. Bertucci, A. Peister, D. J. Weiss, V. G. Valentine, D. J. Prockop, and J. K. Kolls. 2005. Adult stem cells from bone marrow stroma differentiate into airway epithelial cells: potential therapy for cystic fibrosis. Proc. Natl. Acad. Sci. USA 102: 186-191.   DOI   ScienceOn
17 Dripps, D. J., B. J. Brandhuber, R. C. Thompson, and S. P. Eisenberg. 1991. Interleukin-1 (IL-1) receptor antagonist binds to the 80-kDa IL-1 receptor but does not initiate IL-1 signal transduction. J. Biol. Chem. 266: 10331-10336.
18 Friedenstein, A. J., K. V. Petrakova, A. I. Kurolesova, and G. P. Frolova. 1968. Heterotopic of bone marrow; Analysis of precursor cells for osteogenic and hematopoietic tissues. Transplantation 6: 230-247.   DOI   ScienceOn
19 Bernardo, M. E., F. Locatelli, and W. E. Fibbe. 2009. Mesenchymal stromal cells. Ann. N. Y. Acad. Sci. 1176: 101-117   DOI   ScienceOn
20 Choi, H., R. H. Lee, N. Bazhanov, J. Y. Oh, and D. J. Prockop. 2011. Anti-inflammatory protein TSG-6 secreted by activated MSCs attenuates zymosan-induced mouse peritonitis by decreasing TLR2/NF-${\kappa}B$ signaling in resident macrophages. Blood 118: 330-338.   DOI   ScienceOn
21 Dinarello, C. A., A. Simon, and J. W. van der Meer. 2012. Treating inflammation by blocking interleukin-1 in a broad spectrum of diseases. Nat. Rev. Drug Discov. 11: 633-652.   DOI   ScienceOn
22 Deshaies, R. J. and C. A. Joazeiro. 2009. RING domain E3 ubiquitin ligases. Annu. Rev. Biochem. 78: 399-434.   DOI   ScienceOn
23 Li, W., M. H. Bengtson, A. Ulbrich, A. Matsuda, V. A. Reddy, A. Orth, S. K. Chanda, S. Batalov, and C. A. Joazeiro. 2008. Genome-wide and functional annotation of human E3 ubiquitin ligases identifies MULAN, a mitochondrial E3 that regulates the organelle's dynamics and signaling. PLoS One 3: e1487.   DOI   ScienceOn
24 Prockop, D. J. and J. Y. Oh. 2012. Mesenchymal stem/stromal cells (MSCs): role as guardians of inflammation. Mol. Ther. 20: 14-20.   DOI
25 Rotin, D. and S. Kumar. 2009. Physiological functions of the HECT family of ubiquitin ligases. Nat. Rev. Mol. Cell Biol. 10: 398-409.   DOI   ScienceOn
26 Schwamborn, J. C., M. Muller, A. H. Becker, and A. W. Puschel. 2007. Ubiquitination of the GTPase Rap1B by the ubiquitin ligase Smurf2 is required for the establishment of neuronal polarity. EMBO J. 26: 1410-1422.   DOI   ScienceOn
27 Bryan, B., Y. Cai, K. Wrighton, G. Wu, X. H. Feng, and M. Liu. 2005. Ubiquitination of RhoA by Smurf1 promotes neurite outgrowth. FEBS Lett. 579: 1015-1019.   DOI   ScienceOn
28 Lee, R. H., A. A. Pulin, M. J. Seo, D. J. Kota, J. Ylostalo, B. L. Larson, L. Semprun-Prieto, P. Delafontaine, and D. J. Prockop. 2009. Intravenous hMSCs improve myocardial infarction in mice because cells embolized in lung are activated to secrete the anti-inflammatory protein TSG-6. Cell Stem Cell 5: 54-63.   DOI   ScienceOn
29 Oh, J. Y., G. W. Roddy, H. Choi, R. H. Lee, J. H. Ylostalo, R. H. Rosa, Jr., and D. J. Prockop. 2010. Antiinflammatory protein TSG-6 reduces inflammatory damage to the cornea following chemical and mechanical injury. Proc. Natl. Acad. Sci. USA 107: 16875-16880.   DOI   ScienceOn
30 Yamaguchi, S., S. Kuroda, H. Kobayashi, H. Shichinohe, S. Yano, K. Hida, K. Shinpo, S. Kikuchi, and Y. Iwasaki. 2006. The effects of neuronal induction on gene expression profile in bone marrow stromal cells (BMSC)-a preliminary study using microarray analysis. Brain Res. 1087: 15-27.   DOI   ScienceOn
31 Reik, W., W. Dean, and J. Walter. 2001. Epigenetic reprogramming in mammalian development. Science 293: 1089- 1093.   DOI   ScienceOn
32 Jaenisch, R. and A. Bird. 2003. Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals. Nat. Genet. 33 Suppl: 245-254.   DOI   ScienceOn
33 Larsen, F., G. Gundersen, R. Lopez, and H. Prydz. 1992. CpG islands as gene markers in the human genome. Genomics 13: 1095-1107.   DOI
34 Kuwabara, T., J. Hsieh, A. Muotri, G. Yeo, M. Warashina, D. C. Lie, L. Moore, K. Nakashima, M. Asashima, and F. H. Gage. 2009. Wnt-mediated activation of NeuroD1 and retroelements during adult neurogenesis. Nat. Neurosci. 12: 1097- 1105.   DOI   ScienceOn
35 Bird, A. P. and A. P. Wolffe. 1999. Methylation-induced repression-- belts, braces, and chromatin. Cell 99: 451-454.   DOI   ScienceOn
36 Lee, J. E., S. F. Wu, L. M. Goering, and R. I. Dorsky. 2006. Canonical Wnt signaling through Lef1 is required for hypothalamic neurogenesis. Development 133: 4451-4461.   DOI   ScienceOn
37 Toledo, E. M., M. Colombres, and N. C. Inestrosa. 2008. Wnt signaling in neuroprotection and stem cell differentiation. Prog. Neurobiol. 86: 281-296.   DOI   ScienceOn
38 Garcia-Morales, C., C. H. Liu, M. Abu-Elmagd, M. K. Hajihosseini, and G. N. Wheeler. 2009. Frizzled-10 promotes sensory neuron development in Xenopus embryos. Dev. Biol. 335: 143-155.   DOI   ScienceOn
39 Ardley, H. C. and P. A. Robinson. 2005. E3 ubiquitin ligases, Essays Biochem. 41: 15-30.   DOI   ScienceOn
40 Kim, S., O. Honmou, K. Kato, T. Nonaka, K. Houkin, H. Hamada, and J. D. Kocsis. 2006. Neural differentiation potential of peripheral blood- and bone-marrow-derived precursor cells. Brain Res. 1123: 27-33.   DOI   ScienceOn
41 Ankrum, J. and J. M. Karp. 2010. Mesenchymal stem cell therapy: two steps forward, one step back. Trends Mol. Med. 16: 203-209.   DOI   ScienceOn
42 Einstein, O., N. Fainstein, I. Vaknin, R. Mizrachi-Kol, E. Reihartz, N. Grigoriadis, I. Lavon, M. Baniyash, H. Lassmann, and T. Ben-Hur. 2007. Neural precursors attenuate autoimmune encephalomyelitis by peripheral immunosuppression. Ann. Neurol. 61: 209-218.   DOI   ScienceOn
43 Ben-Hur, T. 2008. Immunomodulation by neural stem cells. J. Neurol. Sci. 265: 102-104.   DOI   ScienceOn
44 Rickard, D. J., M. Kassem, T. E. Hefferan, G. Sarkar, T. C. Spelsberg, and B. L. Riggs. 1996. Isolation and characterization of osteoblast precursor cells from human bone marrow. J. Bone Miner. Res. 11: 312-324.
45 Gulacsi, A. A. and S. A. Anderson. 2008. Beta-catenin-mediated Wnt signaling regulates neurogenesis in the ventral telencephalon. Nat. Neurosci. 11: 1383-1391.   DOI   ScienceOn