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Current Drug Delivery

Author(s): Sepehr Soleymani, Amin Hadi, Fatemeh Asgari, Nooshin Haghighipour* and Azam Bolhassani*

DOI: 10.2174/1567201816666190923152914

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Combination of Mechanical and Chemical Methods Improves Gene Delivery in Cell-based HIV Vaccines

Page: [818 - 828] Pages: 11

  • * (Excluding Mailing and Handling)

Abstract

Objective: Novel vaccination approaches are required to control human immunodeficiency virus (HIV) infections. The membrane proximal external region (MPER) of Env gp41 subunit and the V3/glycans of Env gp120 subunit were known as potential antigenic targets for anti-HIV-1 vaccines. In this study, we prepared the modified dendritic cells (DCs) and mesenchymal stem cells (MSCs) with HIV-1 MPER-V3 gene using mechanical and chemical approaches.

Methods: At first, MPER-V3 fusion DNA delivery was optimized in dendritic cells (DCs) and mesenchymal stem cells (MSCs) using three mechanical (i.e., uniaxial cyclic stretch, equiaxial cyclic stretch and shear stress bioreactors), and two chemical (i.e., TurboFect or Lipofectamine) methods. Next, the modified DCs and MSCs with MPER-V3 antigen were compared to induce immune responses in vivo.

Results: Our data showed that the combination of equiaxial cyclic stretch loading and lipofectamine twice with 48 h intervals increased the efficiency of transfection about 60.21 ± 1.05 % and 65.06 ± 0.09 % for MSCs and DCs, respectively. Moreover, DCs and MSCs transfected with MPER-V3 DNA in heterologous DC or MSC prime/ peptide boost immunizations induced high levels of IgG2a, IgG2b, IFN-γ and IL-10 directed toward Th1 responses as well as an increased level of Granzyme B. Indeed, the modified MSCs and DCs with MPER-V3 DNA could significantly enhance the MPER/V3-specific T-cell responses compared to MPER/V3 peptide immunization.

Conclusions: These findings showed that the modified MSC-based immunization could elicit effective immune responses against HIV antigen similar to the modified DC-based immunization.

Keywords: Human immunodeficiency virus (HIV), dendritic cell, mesenchymal stem cell, chemical delivery system, mechanical transfection, immunological assay.

Graphical Abstract

[1]
Ruane, D.; Do, Y.; Brane, L.; Garg, A.; Bozzacco, L.; Kraus, T.; Caskey, M.; Salazar, A.; Trumpheller, C.; Mehandru, S. A dendritic cell targeted vaccine induces long-term HIV-specific immunity within the gastrointestinal tract. Mucosal Immunol., 2016, 9(5), 1340-1352.
[http://dx.doi.org/10.1038/mi.2015.133] [PMID: 26732678]
[2]
Mann, J.K.; Ndung’u, T. HIV-1 vaccine immunogen design strategies. Virol. J., 2015, 12, 3.
[http://dx.doi.org/10.1186/s12985-014-0221-0] [PMID: 25616599]
[3]
Krebs, S.J.; McBurney, S.P.; Kovarik, D.N.; Waddell, C.D.; Jaworski, J.P.; Sutton, W.F.; Gomes, M.M.; Trovato, M.; Waagmeester, G.; Barnett, S.J.; DeBerardinis, P.; Haigwood, N.L. Multimeric scaffolds displaying the HIV-1 envelope MPER induce MPER-specific antibodies and cross-neutralizing antibodies when co-immunized with gp160 DNA. PLoS One, 2014, 9(12)e113463
[http://dx.doi.org/10.1371/journal.pone.0113463] [PMID: 25514675]
[4]
Liu, H.; Su, X.; Si, L.; Lu, L.; Jiang, S. The development of HIV vaccines targeting gp41 membrane-proximal external region (MPER): challenges and prospects. Protein Cell, 2018, 9(7), 596-615.
[http://dx.doi.org/10.1007/s13238-018-0534-7] [PMID: 29667004]
[5]
Molinos-Albert, L.M.; Clotet, B.; Blanco, J.; Carrillo, J. Immunologic insights on the membrane proximal external region: A major human immunodeficiency virus type-1 vaccine target. Front. Immunol., 2017, 8, 1154.
[http://dx.doi.org/10.3389/fimmu.2017.01154] [PMID: 28970835]
[6]
Jacob, R.A.; Moyo, T.; Schomaker, M.; Abrahams, F.; Grau Pujol, B.; Dorfman, J.R. Anti-1 V3/glycan and anti-MPER neutralizing antibodies, but not anti-V2/glycan-site antibodies 2 are strongly associated with higher anti-HIV-1 neutralization breadth and potency. J. Virol., 2015, 89(10), 5264-5275.
[http://dx.doi.org/10.1128/JVI.00129-15] [PMID: 25673728]
[7]
Glass, J.J.; Kent, S.J.; De Rose, R. Enhancing dendritic cell activation and HIV vaccine effectiveness through nanoparticle vaccination. Expert Rev. Vaccines, 2016, 15(6), 719-729.
[http://dx.doi.org/10.1586/14760584.2016.1141054] [PMID: 26783186]
[8]
Lema, D.; Garcia, A.; De Sanctis, J.B. HIV vaccines: a brief overview. Scand. J. Immunol., 2014, 80(1), 1-11.
[http://dx.doi.org/10.1111/sji.12184] [PMID: 24813074]
[9]
Tomchuck, S.L.; Norton, E.B.; Garry, R.F.; Bunnell, B.A.; Morris, C.A.; Freytag, L.C.; Clements, J.D. Mesenchymal stem cells as a novel vaccine platform. Front. Cell. Infect. Microbiol., 2012, 2, 140.
[http://dx.doi.org/10.3389/fcimb.2012.00140] [PMID: 23162801]
[10]
Rinaldo, C.R. Dendritic cell-based human immunodeficiency virus vaccine. J. Intern. Med., 2009, 265(1), 138-158.
[http://dx.doi.org/10.1111/j.1365-2796.2008.02047.x] [PMID: 19093966]
[11]
Janmey, P.A.; McCulloch, C.A. Cell mechanics: Integrating cell responses to mechanical stimuli. Annu. Rev. Biomed. Eng., 2007, 9, 1-34.
[http://dx.doi.org/10.1146/annurev.bioeng.9.060906.151927] [PMID: 17461730]
[12]
Tabas, I.; García-Cardeña, G.; Owens, G.K. Recent insights into the cellular biology of atherosclerosis. J. Cell Biol., 2015, 209(1), 13-22.
[http://dx.doi.org/10.1083/jcb.201412052] [PMID: 25869663]
[13]
Leontiadou, H.; Mark, A.E.; Marrink, S.J. Molecular dynamics simulations of hydrophilic pores in lipid bilayers. Biophys. J., 2004, 86(4), 2156-2164.
[http://dx.doi.org/10.1016/S0006-3495(04)74275-7] [PMID: 15041656]
[14]
Chen, J.; Yuan, Z.; Liu, Y.; Zheng, R.; Dai, Y.; Tao, R.; Xia, H.; Liu, H.; Zhang, Z.; Zhang, W.; Liu, W.; Cao, Y.; Zhou, G. Improvement of in vitro three-dimensional cartilage regeneration by a novel hydrostatic pressure bioreactor. Stem Cells Transl. Med., 2017, 6(3), 982-991.
[http://dx.doi.org/10.5966/sctm.2016-0118] [PMID: 28297584]
[15]
Schroeder, C.; Hoelzer, A.; Zhu, G.; Woiczinski, M.; Betz, O.B.; Graf, H.; Mayer-Wagner, S.; Mueller, P.E. A closed loop perfusion bioreactor for dynamic hydrostatic pressure loading and cartilage tissue engineering. J. Mech. Med. Biol., 2016, 161650025
[http://dx.doi.org/10.1142/S0219519416500251]
[16]
Riehl, B.D.; Park, J.H.; Kwon, I.K.; Lim, J.Y. Mechanical stretching for tissue engineering: Two-dimensional and three-dimensional constructs. Tissue Eng. Part B Rev., 2012, 18(4), 288-300.
[http://dx.doi.org/10.1089/ten.teb.2011.0465] [PMID: 22335794]
[17]
Yeatts, A.B.; Fisher, J.P. Bone tissue engineering bioreactors: Dynamic culture and the influence of shear stress. Bone, 2011, 48(2), 171-181.
[http://dx.doi.org/10.1016/j.bone.2010.09.138] [PMID: 20932947]
[18]
Akimov, S.A.; Volynsky, P.E.; Galimzyanov, T.R.; Kuzmin, P.I.; Pavlov, K.V.; Batishchev, O.V. Pore formation in lipid membrane II: Energy landscape under external stress. Sci. Rep., 2017, 7(1), 12509.
[http://dx.doi.org/10.1038/s41598-017-12749-x] [PMID: 28970526]
[19]
Montani, M.; Marchini, C.; Pazmay, G.V.B. Getting the most from gene delivery by repeated DNA transfections. Appl. Phys. Lett., 2015, 106233701
[http://dx.doi.org/10.1063/1.4922288]
[20]
Bolhassani, A.; Kardani, K.; Vahabpour, R.; Habibzadeh, N.; Aghasadeghi, M.R.; Sadat, S.M.; Agi, E. Prime/boost immunization with HIV-1 MPER-V3 fusion construct enhances humoral and cellular immune responses. Immunol. Lett., 2015, 168(2), 366-373.
[http://dx.doi.org/10.1016/j.imlet.2015.10.012] [PMID: 26518142]
[21]
Strome, S.E.; Voss, S.; Wilcox, R.; Wakefield, T.L.; Tamada, K.; Flies, D.; Chapoval, A.; Lu, J.; Kasperbauer, J.L.; Padley, D.; Vile, R.; Gastineau, D.; Wettstein, P.; Chen, L. Strategies for antigen loading of dendritic cells to enhance the antitumor immune response. Cancer Res., 2002, 62(6), 1884-1889.
[PMID: 11912169]
[22]
Pu, Z.; You, X.; Xu, Q.; Gao, F.; Xie, X.; Zhang, H.; Jian’an, W. Protein expression of mesenchymal stem cells after transfection of pcDNA3.1−-hVEGF165 by ultrasound-targeted microbubble destruction. J. Biomed. Biotechnol., 2011, 2011839653
[http://dx.doi.org/10.1155/2011/839653] [PMID: 21716668]
[23]
Hatami, J.; Tafazzoli-Shadpour, M.; Haghighipour, N.; De Moudt, S.; Martinet, W.; De Meyer, G.R.; Schrijvers, D.M.; De Keulenaer, G.W.; Fransen, P. Influence of cyclic stretch on mechanical properties of endothelial cells. Exp. Mech., 2013, 53, 1291-1298.
[http://dx.doi.org/10.1007/s11340-013-9744-3]
[24]
Kabirian, F.; Amoabediny, G.; Haghighipour, N.; Salehi-Nik, N.; Zandieh-Doulabi, B. Nitric oxide secretion by endothelial cells in response to fluid shear stress, aspirin, and temperature. J. Biomed. Mater. Res. A, 2015, 103(3), 1231-1237.
[http://dx.doi.org/10.1002/jbm.a.35233] [PMID: 24838707]
[25]
Tabatabaei, F.S.; Jazayeri, M.; Ghahari, P.; Haghighipour, N. Effects of equiaxial strain on the differentiation of dental pulp stem cells without using biochemical reagents. Mol. Cell. Biomech., 2014, 11(3), 209-220.
[PMID: 25831861]
[26]
Leontiadou, H.; Mark, A.E.; Marrink, S.J. Molecular dynamics simulations of hydrophilic pores in lipid bilayers. Biophys. J., 2004, 86(4), 2156-2164.
[http://dx.doi.org/10.1016/S0006-3495(04)74275-7] [PMID: 15041656]
[27]
Haghighipour, N.; Tafazzoli-Shadpour, M.; Shokrgozar, M.A.; Amini, S.; Amanzadeh, A.; Khorasani, M.T. Topological remodeling of cultured endothelial cells by characterized cyclic strains. Mol. Cell. Biomech., 2007, 4(4), 189-199.
[PMID: 18437916]
[28]
Shojaei, S.; Tafazzoli-Shahdpour, M.; Shokrgozar, M.A. The influence of cyclic and uniform shear stresses concurrent with cyclic stretch on the gene expression of human umbilical vein endothelial cells. J. Biomater. Tissue Eng., 2013, 3, 673-678.
[http://dx.doi.org/10.1166/jbt.2013.1129]
[29]
Bolhassani, A.; Shahbazi, S.; Milani, A.; Nadji, S.A. Small heat shock proteins B1 and B6: Which one is the most effective adjuvant in therapeutic HPV vaccine? IUBMB Life, 2018, 70(10), 1002-1011.
[http://dx.doi.org/10.1002/iub.1892] [PMID: 30171788]
[30]
Steward, A.J.; Kelly, D.J. Mechanical regulation of mesenchymal stem cell differentiation. J. Anat., 2015, 227(6), 717-731.
[http://dx.doi.org/10.1111/joa.12243] [PMID: 25382217]
[31]
Urbanova, L.; Hradilova, N.; Moserova, I.; Vosahlikova, S.; Sadilkova, L.; Hensler, M.; Spisek, R.; Adkins, I. High hydrostatic pressure affects antigenic pool in tumor cells: Implication for dendritic cell-based cancer immunotherapy. Immunol. Lett., 2017, 187, 27-34.
[http://dx.doi.org/10.1016/j.imlet.2017.05.005] [PMID: 28495513]
[32]
Safshekan, F.; Tafazzoli Shadpour, M.; Shokrgozar, M.A. Effects of short-term cyclic hydrostatic pressure on initiating and enhancing the expression of chondrogenic genes in human adipose-derived mesenchymal stem cells. J. Mech. Med. Biol., 2014, 141450054
[http://dx.doi.org/10.1142/S0219519414500547]
[33]
Cui, Y.; Hameed, F.M.; Yang, B.; Lee, K.; Pan, C.Q.; Park, S.; Sheetz, M. Cyclic stretching of soft substrates induces spreading and growth. Nat. Commun., 2015, 6, 6333.
[http://dx.doi.org/10.1038/ncomms7333] [PMID: 25704457]
[34]
Mihic, A.; Li, J.; Miyagi, Y.; Gagliardi, M.; Li, S.H.; Zu, J.; Weisel, R.D.; Keller, G.; Li, R.K. The effect of cyclic stretch on maturation and 3D tissue formation of human embryonic stem cell-derived cardiomyocytes. Biomaterials, 2014, 35(9), 2798-2808.
[http://dx.doi.org/10.1016/j.biomaterials.2013.12.052] [PMID: 24424206]
[35]
Chang, J.; Xia, Y.; Wasserloos, K.; Deng, M.; Blose, K.J.; Vorp, D.A.; Turnquist, H.R.; Billiar, T.R.; Pitt, B.A.; Zhang, M.Z.; Zhang, L.M. Cyclic stretch induced IL-33 production through HMGB1/TLR-4 signaling pathway in murine respiratory epithelial cells. PLoS One, 2017, 12(9) e0184770
[http://dx.doi.org/10.1371/journal.pone.0184770] [PMID: 28898270]
[36]
Chistiakov, D.A.; Orekhov, A.N.; Bobryshev, Y.V. Effects of shear stress on endothelial cells: Go with the flow. Acta Physiol. (Oxf.), 2017, 219(2), 382-408.
[http://dx.doi.org/10.1111/apha.12725] [PMID: 27246807]
[37]
Hosseini, M.S.; Tafazzoli-Shadpour, M.; Haghighipour, N.; Aghdami, N.; Goodarzi, A. The synergistic effects of shear stress and cyclic hydrostatic pressure modulate chondrogenic induction of human mesenchymal stem cells. Int. J. Artif. Organs, 2015, 38(10), 557-564.
[http://dx.doi.org/10.5301/ijao.5000433] [PMID: 26541277]
[38]
Rashidi, N.; Tafazzoli-Shadpour, M.; Haghighipour, N.; Khani, M.M. Morphology and contractile gene expression of adiposederived mesenchymal stem cells in response to short-term cyclic uniaxial strain and TGF-β1. Biomedical Engineering/Biomedizinische Technik, 2018, 63, 317-26.
[39]
Sharp, L.A.; Lee, Y.W.; Goldstein, A.S. Effect of low-frequency pulsatile flow on expression of osteoblastic genes by bone marrow stromal cells. Ann. Biomed. Eng., 2009, 37(3), 445-453.
[http://dx.doi.org/10.1007/s10439-008-9632-7] [PMID: 19130228]
[40]
Chen, J.C.; Jacobs, C.R. Mechanically induced osteogenic lineage commitment of stem cells. Stem Cell Res. Ther., 2013, 4(5), 107.
[http://dx.doi.org/10.1186/scrt318] [PMID: 24004875]
[41]
Riddle, R.C.; Hippe, K.R.; Donahue, H.J. Chemotransport contributes to the effect of oscillatory fluid flow on human bone marrow stromal cell proliferation. J. Orthop. Res., 2008, 26(7), 918-924.
[http://dx.doi.org/10.1002/jor.20637] [PMID: 18327808]
[42]
Kearney, E.M.; Prendergast, P.J.; Campbell, V.A. Mechanisms of strain-mediated mesenchymal stem cell apoptosis. J. Biomech. Eng., 2008, 130(6) 061004
[http://dx.doi.org/10.1115/1.2979870] [PMID: 19045533]
[43]
Liu, C.; Yu, Y.; Miao, L. A comparative study of transfection of rat mesenchymal stem cells using polyethyleneimine-coated magnetic ferro-ferric oxide nanoparticles and lipofectamine. Int. J. Clin. Exp. Med., 2016, 9, 6062-6069.
[44]
Cerver, L. GutieÂrrez-Granados, S.; Berrow, N.S.; Segura, M.M.; Gòdia, F. Extended gene expression by medium exchange and repeated transient transfection for recombinant protein production enhancement. Biotechnol. Bioeng., 2014, 9999, 1-13.
[45]
Rahma, O.E.; Herrin, V.E.; Ibrahim, R.A.; Toubaji, A.; Bernstein, S.; Dakheel, O.; Steinberg, S.M.; Abu Eid, R.; Mkrtichyan, M.; Berzofsky, J.A.; Khleif, S.N. Pre-immature dendritic cells (PIDC) pulsed with HPV16 E6 or E7 peptide are capable of eliciting specific immune response in patients with advanced cervical cancer. J. Transl. Med., 2014, 12, 353.
[http://dx.doi.org/10.1186/s12967-014-0353-4] [PMID: 25510844]
[46]
Majumdar, M.K.; Keane-Moore, M.; Buyaner, D.; Hardy, W.B.; Moorman, M.A.; McIntosh, K.R.; Mosca, J.D. Characterization and functionality of cell surface molecules on human mesenchymal stem cells. J. Biomed. Sci., 2003, 10(2), 228-241.
[http://dx.doi.org/10.1007/BF02256058] [PMID: 12595759]
[47]
Stagg, J. Immune regulation by mesenchymal stem cells: two sides to the coin. Tissue Antigens, 2007, 69(1), 1-9.
[http://dx.doi.org/10.1111/j.1399-0039.2006.00739.x] [PMID: 17212702]
[48]
François, M.; Romieu-Mourez, R.; Stock-Martineau, S.; Boivin, M.N.; Bramson, J.L.; Galipeau, J. Mesenchymal stromal cells cross-present soluble exogenous antigens as part of their antigen-presenting cell properties. Blood, 2009, 114(13), 2632-2638.
[http://dx.doi.org/10.1182/blood-2009-02-207795] [PMID: 19654411]
[49]
Tomchuck, S.L.; Zwezdaryk, K.J.; Coffelt, S.B.; Waterman, R.S.; Danka, E.S.; Scandurro, A.B. Toll-like receptors on human mesenchymal stem cells drive their migration and immunomodulating responses. Stem Cells, 2008, 26(1), 99-107.
[http://dx.doi.org/10.1634/stemcells.2007-0563] [PMID: 17916800]
[50]
Waterman, R.S.; Tomchuck, S.L.; Henkle, S.L.; Betancourt, A.M. A new mesenchymal stem cell (MSC) paradigm: polarization into a pro-inflammatory MSC1 or an Immunosuppressive MSC2 phenotype. PLoS One, 2010, 5(4) e10088
[http://dx.doi.org/10.1371/journal.pone.0010088] [PMID: 20436665]