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http://dx.doi.org/10.14348/molcells.2017.0095

Effects of Adenoviral Gene Transduction on the Stemness of Human Bone Marrow Mesenchymal Stem Cells  

Marasini, Subash (Department of Anatomy, Ajou University School of Medicine)
Chang, Da-Young (Department of Anatomy, Ajou University School of Medicine)
Jung, Jin-Hwa (Department of Anatomy, Ajou University School of Medicine)
Lee, Su-Jung (Department of Anatomy, Ajou University School of Medicine)
Cha, Hye Lim (Department of Anatomy, Ajou University School of Medicine)
Suh-Kim, Haeyoung (Department of Anatomy, Ajou University School of Medicine)
Kim, Sung-Soo (Department of Anatomy, Ajou University School of Medicine)
Publication Information
Molecules and Cells / v.40, no.8, 2017 , pp. 598-605 More about this Journal
Abstract
Human mesenchymal stem cells (MSCs) are currently being evaluated as a cell-based therapy for tissue injury and degenerative diseases. Recently, several methods have been suggested to further enhance the therapeutic functions of MSCs, including genetic modifications with tissue- and/or diseasespecific genes. The objective of this study was to examine the efficiency and stability of transduction using an adenoviral vector in human MSCs. Additionally, we aimed to assess the effects of transduction on the proliferation and multipotency of MSCs. The results indicate that MSCs can be transduced by adenoviruses in vitro, but high viral titers are necessary to achieve high efficiency. In addition, transduction at a higher multiplicity of infection (MOI) was associated with attenuated proliferation and senescence-like morphology. Furthermore, transduced MSCs showed a diminished capacity for adipogenic differentiation while retaining their potential to differentiate into osteocytes and chondrocytes. This work could contribute significantly to clinical trials of MSCs modified with therapeutic genes.
Keywords
adenoviral vector; mesenchymal stem cells; stemness;
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1 Robey, T.E., Saiget, M.K., Reinecke, H., and Murry, C.E. (2008). Systems approaches to preventing transplanted cell death in cardiac repair. J. Mol. Cell Cardiol. 45, 567-581.   DOI
2 Chang, D.Y., Yoo, S.W., Hong, Y., Kim, S., Kim, S.J., Yoon, S.H., Cho, K.G., Paek, S.H., Lee, Y.D., Kim, S.S., et al. (2010). The growth of brain tumors can be suppressed by multiple transplantation of mesenchymal stem cells expressing cytosine deaminase. Int. J. Cancer 127, 1975-1983.   DOI
3 Chen, R.F., and Lee, C.Y. (2014). Adenoviruses types, cell receptors and local innate cytokines in adenovirus infection. Int. Rev. Immunol. 33, 45-53.   DOI
4 Chen, Y., Shao, J.Z., Xiang, L.X., Dong, X.J., and Zhang, G.R. (2008). Mesenchymal stem cells: a promising candidate in regenerative medicine. Int. J. Biochem. Cell Biol. 40, 815-820.   DOI
5 Conget, P.A., and Minguell, J.J. (2000). Adenoviral-mediated gene transfer into ex vivo expanded human bone marrow mesenchymal progenitor cells. Exp. Hematol. 28, 382-390.   DOI
6 Crystal, R.G. (1999). In vivo and ex vivo gene therapy strategies to treat tumors using adenovirus gene transfer vectors. Cancer Chemother. Pharmacol. 43 Suppl, S90-99.   DOI
7 Deng, Y., Yang, Z., Terry, T., Pan, S., Woodside, D.G., Wang, J., Ruan, K., Willerson, J.T., Dixon, R.A., and Liu, Q. (2016). Prostacyclinproducing human mesenchymal cells target H19 lncRNA to augment endogenous progenitor function in hindlimb ischaemia. Nat. Commun. 7, 11276.   DOI
8 Deuse, T., Peter, C., Fedak, P.W., Doyle, T., Reichenspurner, H., Zimmermann, W.H., Eschenhagen, T., Stein, W., Wu, J.C., Robbins, R.C., et al. (2009). Hepatocyte growth factor or vascular endothelial growth factor gene transfer maximizes mesenchymal stem cell-based myocardial salvage after acute myocardial infarction. Circulation 120, S247-254.   DOI
9 Romieu-Mourez, R., Francois, M., Boivin, M.N., Stagg, J., and Galipeau, J., (2007) Regulation of MHC class II expression and antigen processing in murine and human mesenchymal stromal cells by IFN-gamma, TGF-beta, and cell density. J. Immunol. 179, 1549-58.   DOI
10 Suzuki, T., Kawamura, K., Li, Q., Okamoto, S., Tada, Y., Tatsumi, K., Shimada, H., Hiroshima, K., Yamaguchi, N., and Tagawa, M. (2014). Mesenchymal stem cells are efficiently transduced with adenoviruses bearing type 35-derived fibers and the transduced cells with the IL-28A gene produces cytotoxicity to lung carcinoma cells co-cultured. BMC Cancer 14, 713.   DOI
11 Totsugawa, T., Kobayashi, N., Okitsu, T., Noguchi, H., Watanabe, T., Matsumura, T., Maruyama, M., Fujiwara, T., Sakaguchi, M., and Tanaka, N. (2002). Lentiviral transfer of the LacZ gene into human endothelial cells and human bone marrow mesenchymal stem cells. Cell Transplant 11, 481-488.
12 Tsuda, H., Wada, T., Ito, Y., Uchida, H., Dehari, H., Nakamura, K., Sasaki, K., Kobune, M., Yamashita, T., and Hamada, H. (2003). Efficient BMP2 gene transfer and bone formation of mesenchymal stem cells by a fiber-mutant adenoviral vector. Mol. Ther. 7, 354-365.   DOI
13 Vorburger, S.A., and Hunt, K.K. (2002). Adenoviral gene therapy. Oncologist 7, 46-59.
14 Wang, W.Q., Dong, K., Zhou, L., Jiao, G.H., Zhu, C.Z., Li, W.W., Yu, G., Wu, W.T., Chen, S., Sun, Z.N., et al. (2015). IL-37b gene transfer enhances the therapeutic efficacy of mesenchumal stromal cells in DSS-induced colitis mice. Acta Pharmacol. Sin 36, 1377-1387.   DOI
15 www.clinicaltrials.gov (2017). The United States National Institutes of Health Clinical Trial Database.
16 Hung, S.C., Lu, C.Y., Shyue, S.K., Liu, H.C., and Ho, L.L. (2004). Lineage differentiation-associated loss of adenoviral susceptibility and Coxsackie-adenovirus receptor expression in human mesenchymal stem cells. Stem Cells 22, 1321-1329.   DOI
17 Garza-Veloz, I., Romero-Diaz, V.J., Martinez-Fierro, M.L., Marino- Martinez, I.A., Gonzalez-Rodriguez, M., Martinez-Rodriguez, H.G., Espinoza-Juarez, M.A., Bernal-Garza, D.A., Ortiz-Lopez, R., and Rojas-Martinez, A. (2013). Analyses of chondrogenic induction of adipose mesenchymal stem cells by combined co-stimulation mediated by adenoviral gene transfer. Arthritis Res. Ther. 15, R80.   DOI
18 Gerard, R.D., and Collen, D. (1997). Adenovirus gene therapy for hypercholesterolemia, thrombosis and restenosis. Cardiovasc. Res. 35, 451-458.   DOI
19 Haleem-Smith, H., Derfoul, A., Okafor, C., Tuli, R., Olsen, D., Hall, D.J., and Tuan, R.S. (2005). Optimization of high-efficiency transfection of adult human mesenchymal stem cells in vitro. Mol. Biotechnol. 30, 9-20.   DOI
20 Hocking, A.M., and Gibran, N.S. (2010). Mesenchymal stem cells: paracrine signaling and differentiation during cutaneous wound repair. Exp. Cell Res. 316, 2213-2219.   DOI
21 Ju, X.D., Lou, S.Q., Wang, W.G., Peng, J.Q., and Tian, H. (2004). Effect of hydroxyurea and etoposide on transduction of human bone marrow mesenchymal stem and progenitor cell by adeno-associated virus vectors. Acta Pharmacol. Sin. 25, 196-202.
22 Kim, M.D., Kim, S.S., Cha, H.Y., Jang, S.H., Chang, D.Y., Kim, W., Suh-Kim, H., and Lee, J.H. (2014). Therapeutic effect of hepatocyte growth factor-secreting mesenchymal stem cells in a rat model of liver fibrosis. Exp. Mol. Med. 46, e110.   DOI
23 Larsen, S., and Lewis, I.D. (2011). Potential therapeutic applications of mesenchymal stromal cells. Pathology 43, 592-604.   DOI
24 Zhang, X.Y., La Russa, V.F., and Reiser, J. (2004). Transduction of bone-marrow-derived mesenchymal stem cells by using lentivirus vectors pseudotyped with modified RD114 envelope glycoproteins. J. Virol. 78, 1219-1229.   DOI
25 Zhang, Y., and Bergelson, J.M. (2005). Adenovirus receptors. J. Virol. 79, 12125-12131.   DOI
26 Kim, S.S., Choi, J.M., Kim, J.W., Ham, D.S., Ghil, S.H., Kim, M.K., Kim-Kwon, Y., Hong, S.Y., Ahn, S.C., Kim, S.U., et al. (2005). cAMP induces neuronal differentiation of mesenchymal stem cells via activation of extracellular signal-regulated kinase/MAPK. Neuroreport 16, 1357-1361.   DOI
27 Kim, S.S., Yoo, S.W., Park, T.S., Ahn, S.C., Jeong, H.S., Kim, J.W., Chang, D.Y., Cho, K.G., Kim, S.U., Huh, Y., et al. (2008). Neural induction with neurogenin1 increases the therapeutic effects of mesenchymal stem cells in the ischemic brain. Stem Cells 26, 2217-2228.   DOI
28 Kumar, S., Mahendra, G., Nagy, T.R., and Ponnazhagan, S. (2004). Osteogenic differentiation of recombinant adeno-associated virus 2-transduced murine mesenchymal stem cells and development of an immunocompetent mouse model for ex vivo osteoporosis gene therapy. Hum Gene Ther. 15, 1197-1206.   DOI
29 Lee, C.I., Kohn, D.B., Ekert, J.E., and Tarantal, A.F. (2004). Morphological analysis and lentiviral transduction of fetal monkey bone marrow-derived mesenchymal stem cells. Mol. Ther. 9, 112-123.
30 Lou, J., Xu, F., Merkel, K., and Manske, P. (1999). Gene therapy: adenovirus-mediated human bone morphogenetic protein-2 gene transfer induces mesenchymal progenitor cell proliferation and differentiation in vitro and bone formation in vivo. J. Orthop. Res. 17, 43-50.   DOI
31 Lu, L., Zhao, C., Liu, Y., Sun, X., Duan, C., Ji, M., Zhao, H., Xu, Q., and Yang, H. (2005). Therapeutic benefit of TH-engineered mesenchymal stem cells for Parkinson's disease. Brain Res Brain Res. Protoc. 15, 46-51.   DOI
32 Moutsatsos, I.K., Turgeman, G., Zhou, S., Kurkalli, B.G., Pelled, G., Tzur, L., Kelley, P., Stumm, N., Mi, S., Muller, R., et al. (2001). Exogenously regulated stem cell-mediated gene therapy for bone regeneration. Mol Ther 3, 449-461.   DOI
33 McMahon, J.M., Conroy, S., Lyons, M., Greiser, U., O'Shea, C., Strappe, P., Howard, L., Murphy, M., Barry, F., and O'Brien, T. (2006). Gene transfer into rat mesenchymal stem cells: a comparative study of viral and nonviral vectors. Stem Cells Dev. 15, 87-96.   DOI
34 Meirelles Lda, S., Fontes, A.M., Covas, D.T., and Caplan, A.I. (2009). Mechanisms involved in the therapeutic properties of mesenchymal stem cells. Cytokine Growth Factor Rev. 20, 419-427.   DOI
35 Moon, H.H., Joo, M.K., Mok, H., Lee, M., Hwang, K.C., Kim, S.W., Jeong, J.H., Choi, D., and Kim, S.H. (2014). MSC-based VEGF gene therapy in rat myocardial infarction model using facial amphipathic bile acid-conjugated polyethyleneimine. Biomaterials 35, 1744-1754.   DOI
36 Musgrave, D.S., Bosch, P., Ghivizzani, S., Robbins, P.D., Evans, C.H., and Huard, J. (1999). Adenovirus-mediated direct gene therapy with bone morphogenetic protein-2 produces bone. Bone 24, 541-547.   DOI
37 Park, J.S., Suryaprakash, S., Lao, Y.H., and Leong, K.W. (2015). Engineering mesenchymal stem cells for regenerative medicine and drug delivery. Methods 84, 3-16.   DOI
38 Peterson, B., Zhang, J., Iglesias, R., Kabo, M., Hedrick, M., Benhaim, P., and Lieberman, J.R. (2005). Healing of critically sized femoral defects, using genetically modified mesenchymal stem cells from human adipose tissue. Tissue Eng. 11, 120-129.   DOI
39 Boregowda, S.V., and Phinney, D.G. (2012). Therapeutic applications of mesenchymal stem cells: current outlook. BioDrugs 26, 201-208.   DOI
40 Ansari, A.M., Ahmed, A.K., Matsangos, A.E., Lay, F., Born, L.J., Marti, G., Harmon, J.W., and Sun, Z. (2016). Cellular GFP toxicity and immunogenicity: potential confounders in in vivo cell tracking experiments. Stem Cell Rev. 12, 553-559.   DOI
41 Bosch, P., Fouletier-Dilling, C., Olmsted-Davis, E.A., Davis, A.R., and Stice, S.L. (2006). Efficient adenoviral-mediated gene delivery into porcine mesenchymal stem cells. Mol. Reprod. Dev. 73, 1393-1403.   DOI
42 Breyer, B., Jiang, W., Cheng, H., Zhou, L., Paul, R., Feng, T., and He, T.C. (2001). Adenoviral vector-mediated gene transfer for human gene therapy. Curr. Gene Ther. 1, 149-162.   DOI
43 Byun, H.M., Suh, D., Jeong, Y., Wee, H.S., Kim, J.M., Kim, W.K., Ko, J.J., Kim, J.S., Lee, Y.B., and Oh, Y.K. (2005). Plasmid vectors harboring cellular promoters can induce prolonged gene expression in hematopoietic and mesenchymal progenitor cells. Biochem. Biophys. Res. Commun. 332, 518-523.   DOI
44 Chan-Il, C., Young-Don, L., Heejaung, K., Kim, S.H., Suh-Kim, H., and Kim, S.S. (2013). Neural induction with neurogenin 1 enhances the therapeutic potential of mesenchymal stem cells in an amyotrophic lateral sclerosis mouse model. Cell Transplant. 22, 855-870.   DOI
45 Pittenger, M.F., Mackay, A.M., Beck, S.C., Jaiswal, R.K., Douglas, R., Mosca, J.D., Moorman, M.A., Simonetti, D.W., Craig, S., and Marshak, D.R. (1999). Multilineage potential of adult human mesenchymal stem cells. Science 284, 143-147.   DOI