Review Article

Gene-based Therapeutic Tools in the Treatment of Cornea Disease

Author(s): Xiao-Xiao Lu and Shao-Zhen Zhao*

Volume 19, Issue 1, 2019

Page: [7 - 19] Pages: 13

DOI: 10.2174/1566523219666181213120634

Price: $65

Open Access Journals Promotions 2
Abstract

Background: As one of the main blinding ocular diseases, corneal blindness resulted from neovascularization that disrupts the angiogenic privilege of corneal avascularity. Following neovascularization, inflammatory cells are infiltrating into cornea to strengthen corneal injury. How to maintain corneal angiogenic privilege to treat corneal disease has been investigated for decades.

Methodology: Local administration of viral and non-viral-mediated anti-angiogenic factors reduces angiogenic protein expression in situ with limited or free of off-target effects upon gene delivery. Recently, Mesenchymal Stem Cells (MSCs) have been studied to treat corneal diseases. Once MSCs are manipulated to express certain genes of interest, they could achieve superior therapeutic efficacy after transplantation.

Discussion: In the text, we first introduce the pathological development of corneal disease in the aspects of neovascularization and inflammation. We summarize how MSCs become an ideal candidate in cell therapy for treating injured cornea, focusing on cell biology, property and features. We provide an updated review of gene-based therapies in animals and preclinical studies in the aspects of controlling target gene expression, safety and efficacy. Gene transfer vectors are potent to induce candidate protein expression. Delivered by vectors, MSCs are equipped with certain characters by expressing a protein of interest, which facilitates better for MSC-mediated therapeutic intervention for the treatment of corneal disease.

Conclusion: As the core of this review, we discuss how MSCs could be engineered to be vector system to achieve enhanced therapeutic efficiency after injection.

Keywords: Gene therapy, mesenchymal stem cells, corneal disease, inflammation, VEGF, αSMA.

Graphical Abstract
[1]
Ellenberg D, Azar DT, Hallak JA, et al. Novel aspects of corneal angiogenic and lymphangiogenic privilege. Prog Retin Eye Res 2010; 29(3): 208-48.
[2]
Azar DT. Corneal angiogenic privilege: Angiogenic and antiangiogenic factors in corneal avascularity, vasculogenesis, and wound healing (an american ophthalmological society thesis). Trans Am Ophthalmol Soc 2006; 104: 264-302.
[3]
Regenfuss B, Bock F, Parthasarathy A, Cursiefen C. Corneal (lymph)angiogenesis--from bedside to bench and back: A tribute to judah folkman. Lymphat Res Biol 2008; 6(3-4): 191-201.
[4]
Cursiefen C. Immune privilege and angiogenic privilege of the cornea. Chem Immunol Allergy 2007; 92: 50-7.
[5]
Kezuka T, Streilein JW. Evidence for multiple cd95-cd95 ligand interactions in anteriorchamber-associated immune deviation induced by soluble protein antigen. Immunology 2000; 99(3): 451-7.
[6]
Ambati BK, Nozaki M, Singh N, et al. Corneal avascularity is due to soluble vegf receptor-1. Nature 2006; 443(7114): 993-7.
[7]
Albuquerque RJ, Hayashi T, Cho WG, et al. Alternatively spliced vascular endothelial growth factor receptor-2 is an essential endogenous inhibitor of lymphatic vessel growth. Nat Med 2009; 15(9): 1023-30.
[8]
Singh N, Tiem M, Watkins R, et al. Soluble vascular endothelial growth factor receptor 3 is essential for corneal alymphaticity. Blood 2013; 121(20): 4242-9.
[9]
Ksander BR, Kolovou PE, Wilson BJ, et al. Abcb5 is a limbal stem cell gene required for corneal development and repair. Nature 2014; 511(7509): 353-7.
[10]
Ouyang H, Xue Y, Lin Y, et al. Wnt7a and pax6 define corneal epithelium homeostasis and pathogenesis. Nature 2014; 511(7509): 358-61.
[11]
Cursiefen C, Masli S, Ng TF, et al. Roles of thrombospondin-1 and -2 in regulating corneal and iris angiogenesis. Invest Ophthalmol Vis Sci 2004; 45(4): 1117-24.
[12]
Makino Y, Cao R, Svensson K, et al. Inhibitory pas domain protein is a negative regulator of hypoxia-inducible gene expression. Nature 2001; 414(6863): 550-4.
[13]
Liu S, Romano V, Steger B, Kaye SB, Hamill KJ, Willoughby CE. Gene-based antiangiogenic applications for corneal neovascularization. Surv Ophthalmol 2018; 63(2): 193-213.
[14]
Polverini PJ. The pathophysiology of angiogenesis. Crit Rev Oral Biol Med 1995; 6(3): 230-47.
[15]
Hamrah P, Dana MR. Corneal antigen-presenting cells. Chem Immunol Allergy 2007; 92: 58-70.
[16]
Cursiefen C, Chen L, Borges LP, et al. Vegf-a stimulates lymphangiogenesis and hemangiogenesis in inflammatory neovascularization via macrophage recruitment. J Clin Invest 2004; 113(7): 1040-50.
[17]
Cursiefen C, Maruyama K, Bock F, et al. Thrombospondin 1 inhibits inflammatory lymphangiogenesis by cd36 ligation on monocytes. J Exp Med 2011; 208(5): 1083-92.
[18]
Jester JV, Barry-Lane PA, Petroll WM, Olsen DR, Cavanagh HD. Inhibition of corneal fibrosis by topical application of blocking antibodies to tgf beta in the rabbit. Cornea 1997; 16(2): 177-87.
[19]
Torricelli AA, Santhanam A, Wu J, Singh V, Wilson SE. The corneal fibrosis response to epithelial-stromal injury. Exp Eye Res 2016; 142: 110-8.
[20]
Jester JV. Corneal crystallins and the development of cellular transparency. Semin Cell Dev Biol 2008; 19(2): 82-93.
[21]
Jester JV, Brown D, Pappa A, Vasiliou V. Myofibroblast differentiation modulates keratocyte crystallin protein expression, concentration, and cellular light scattering. Invest Ophthalmol Vis Sci 2012; 53(2): 770-8.
[22]
Mittal SK, Omoto M, Amouzegar A, et al. Restoration of corneal transparency by mesenchymal stem cells. Stem Cell Reports 2016; 7(4): 583-90.
[23]
Hua J, Jin Y, Chen Y, et al. The resolvin d1 analogue controls maturation of dendritic cells and suppresses alloimmunity in corneal transplantation. Invest Ophthalmol Vis Sci 2014; 55(9): 5944-51.
[24]
Inomata T, Mashaghi A, Di Zazzo A, Lee SM, Chiang H, Dana R. Kinetics of angiogenic responses in corneal transplantation. Cornea 2017; 36(4): 491-6.
[25]
Amouzegar A, Chauhan SK, Dana R. Alloimmunity and tolerance in corneal transplantation. J Immunol 2016; 196(10): 3983-91.
[26]
Dohlman TH, Di Zazzo A, Omoto M, et al. E-selectin mediates immune cell trafficking in corneal transplantation. Transplantation 2016; 100(4): 772-80.
[27]
Chung ES, Saban DR, Chauhan SK, Dana R. Regulation of blood vessel versus lymphatic vessel growth in the cornea. Invest Ophthalmol Vis Sci 2009; 50(4): 1613-8.
[28]
Li F. Mesenchymal stem cells: Potential role in corneal wound repair and transplantation. World J Stem Cells 2014; 6(3): 296.
[29]
Boneham GC, Collin HB. Steroid inhibition of limbal blood and lymphatic vascular cell growth. Curr Eye Res 1995; 14(1): 1-10.
[30]
Phillips K, Arffa R, Cintron C, et al. Effects of prednisolone and medroxyprogesterone on corneal wound healing, ulceration, and neovascularization. Arch Ophthalmol 1983; 101(4): 640-3.
[31]
Crum R, Szabo S, Folkman J. A new class of steroids inhibits angiogenesis in the presence of heparin or a heparin fragment. Science 1985; 230(4732): 1375-8.
[32]
Joussen AM, Kruse FE, Volcker HE, Kirchhof B. Topical application of methotrexate for inhibition of corneal angiogenesis. Graefes Arch Clin Exp Ophthalmol 1999; 237(11): 920-7.
[33]
You IC, Im SK, Lee SH, Yoon KC. Photodynamic therapy with verteporfin combined with subconjunctival injection of bevacizumab for corneal neovascularization. Cornea 2011; 30(1): 30-3.
[34]
Ambati BK, Joussen AM, Ambati J, et al. Angiostatin inhibits and regresses corneal neovascularization. Arch Ophthalmol 2002; 120(8): 1063-8.
[35]
Chang JH, Garg NK, Lunde E, Han KY, Jain S, Azar DT. Corneal neovascularization: An anti-vegf therapy review. Surv Ophthalmol 2012; 57(5): 415-29.
[36]
Bayar SA, Altinors DD, Kucukerdonmez C, Akova YA. Severe corneal changes following intravitreal injection of bevacizumab. Ocul Immunol Inflamm 2010; 18(4): 268-74.
[37]
Kersey JP, Broadway DC. Corticosteroid-induced glaucoma: A review of the literature. Eye (Lond) 2006; 20(4): 407-16.
[38]
Kim TI, Chung JL, Hong JP, Min K, Seo KY, Kim EK. Bevacizumab application delays epithelial healing in rabbit cornea. Invest Ophthalmol Vis Sci 2009; 50(10): 4653-9.
[39]
Wirostko B, Rafii M, Sullivan DA, Morelli J, Ding J. Novel therapy to treat corneal epithelial defects: A hypothesis with growth hormone. Ocul Surf 2015; 13(3): 204-12.
[40]
Hughes L, Lockington D, Mantry S, Ramaesh K. Novel matrix regenerating agent promotes rapid corneal wound healing. Clin Experiment Ophthalmol 2015; 43(4): 391-2.
[41]
Lee YK, Lin YC, Tsai SH, Chen WL, Chen YM. Therapeutic outcomes of combined topical autologous serum eye drops with silicone-hydrogel soft contact lenses in the treatment of corneal persistent epithelial defects: A preliminary study. Cont Lens Anterior Eye 2016; 39(6): 425-30.
[42]
Tsubota K, Goto E, Fujita H, et al. Treatment of dry eye by autologous serum application in sjogren’s syndrome. Br J Ophthalmol 1999; 83(4): 390-5.
[43]
Pan Q, Angelina A, Marrone M, Stark WJ, Akpek EK. Autologous serum eye drops for dry eye. Cochrane Database Syst Rev 2017; 2: CD009327.
[44]
Nguyen NX, Seitz B, Martus P, Langenbucher A, Cursiefen C. Long-term topical steroid treatment improves graft survival following normal-risk penetrating keratoplasty. Am J Ophthalmol 2007; 144(2): 318-9.
[45]
O’Doherty M, Murphy CC. Update on immunosuppressive therapy for corneal transplantation. Int Ophthalmol Clin 2010; 50(3): 113-22.
[46]
Klausner EA, Peer D, Chapman RL, Multack RF, Andurkar SV. Corneal gene therapy. J Control Release 2007; 124(3): 107-33.
[47]
Mohan RR, Rodier JT, Sharma A. Corneal gene therapy: Basic science and translational perspective. Ocul Surf 2013; 11(3): 150-64.
[48]
Mohan RR, Tovey JC, Sharma A, Tandon A. Gene therapy in the cornea: 2005--present. Prog Retin Eye Res 2012; 31(1): 43-64.
[49]
Ge HY, Xiao N, Yin XL, et al. Comparison of the antiangiogenic activity of modified rgdrgd-endostatin to endostatin delivered by gene transfer in vivo rabbit neovascularization model. Mol Vis 2011; 17: 1918-28.
[50]
Saika S, Yamanaka O, Okada Y, et al. Effect of overexpression of ppargamma on the healing process of corneal alkali burn in mice. Am J Physiol Cell Physiol 2007; 293(1): C75-86.
[51]
Fuchsluger TA, Jurkunas U, Kazlauskas A, Dana R. Anti-apoptotic gene therapy prolongs survival of corneal endothelial cells during storage. Gene Ther 2011; 18(8): 778-87.
[52]
Yuan J, Liu Y, Huang W, Zhou S, Ling S, Chen J. The experimental treatment of corneal graft rejection with the interleukin-1 receptor antagonist (il-1ra) gene. PLoS One 2013; 8(5): e60714.
[53]
Parker DG, Coster DJ, Brereton HM, et al. Lentivirus-mediated gene transfer of interleukin 10 to the ovine and human cornea. Clin Experiment Ophthalmol 2010; 38(4): 405-13.
[54]
Gong N, Pleyer U, Volk HD, Ritter T. Effects of local and systemic viral interleukin-10 gene transfer on corneal allograft survival. Gene Ther 2007; 14(6): 484-90.
[55]
Zhou L, Zhu X, Tan J, Wang J, Xing Y. Effect of recombinant adeno-associated virus mediated transforming growth factor-beta1 on corneal allograft survival after high-risk penetrating keratoplasty. Transpl Immunol 2013; 28(4): 164-9.
[56]
Fouladi N, Parker M, Kennedy V, et al. Safety and efficacy of OXB-202, a genetically-engineered tissue therapy for the prevention of rejection in high risk corneal transplant patients. Hum Gene Ther 2018; 29(6): 687-98.
[57]
Qin Q, Luo D, Shi Y, et al. Cd25 SIRNA induces treg/th1 cytokine expression in rat corneal transplantation models. Exp Eye Res 2016; 151: 134-41.
[58]
Qin Q, Shi Y, Zhao Q, et al. Effects of cd25sirna gene transfer on high-risk rat corneal graft rejection. Graefes Arch Clin Exp Ophthalmol 2015; 253(10): 1765-76.
[59]
Pillai RG, Beutelspacher SC, Larkin DF, George AJ. Expression of the chemokine antagonist vmip ii using a non-viral vector can prolong corneal allograft survival. Transplantation 2008; 85(11): 1640-7.
[60]
Gong N, Pleyer U, Vogt K, et al. Local overexpression of nerve growth factor in rat corneal transplants improves allograft survival. Invest Ophthalmol Vis Sci 2007; 48(3): 1043-52.
[61]
Kaufmann C, Mortimer LA, Brereton HM, et al. Interleukin-10 gene transfer in rat limbal transplantation. Curr Eye Res 2017; 42(11): 1426-34.
[62]
Klebe S, Sykes PJ, Coster DJ, Krishnan R, Williams KA. Prolongation of sheep corneal allograft survival by ex vivo transfer of the gene encoding interleukin-10. Transplantation 2001; 71(9): 1214-20.
[63]
Barcia RN, Dana MR, Kazlauskas A. Corneal graft rejection is accompanied by apoptosis of the endothelium and is prevented by gene therapy with bcl-xl. Am J Transplant 2007; 7(9): 2082-9.
[64]
Pastak M, Kleff V, Saban DR, et al. Gene therapy for modulation of t-cell-mediated immune response provoked by corneal transplantation. Hum Gene Ther 2018; 29(4): 467-79.
[65]
Fuchsluger TA, Jurkunas U, Kazlauskas A, Dana R. Corneal endothelial cells are protected from apoptosis by gene therapy. Hum Gene Ther 2011; 22(5): 549-58.
[66]
Beutelspacher SC, Pillai R, Watson MP, et al. Function of indoleamine 2, 3-dioxygenase in corneal allograft rejection and prolongation of allograft survival by over-expression. Eur J Immunol 2006; 36(3): 690-700.
[67]
Fabian D, Gong N, Vogt K, Volk HD, Pleyer U, Ritter T. The influence of inducible costimulator fusion protein (icosig) gene transfer on corneal allograft survival. Graefes Arch Clin Exp Ophthalmol 2007; 245(10): 1515-21.
[68]
Gong N, Pleyer U, Yang J, et al. Influence of local and systemic ctla4ig gene transfer on corneal allograft survival. J Gene Med 2006; 8(4): 459-67.
[69]
Ritter T, Yang J, Dannowski H, Vogt K, Volk HD, Pleyer U. Effects of interleukin-12p40 gene transfer on rat corneal allograft survival. Transpl Immunol 2007; 18(2): 101-7.
[70]
Jessup CF, Brereton HM, Sykes PJ, Thiel MA, Coster DJ, Williams KA. Local gene transfer to modulate rat corneal allograft rejection. Invest Ophthalmol Vis Sci 2005; 46(5): 1675-81.
[71]
Galiacy SD, Fournie P, Massoudi D, et al. Matrix metalloproteinase 14 overexpression reduces corneal scarring. Gene Ther 2011; 18(5): 462-8.
[72]
Marlo TL, Giuliano EA, Tripathi R, Sharma A, Mohan RR. Altering equine corneal fibroblast differentiation through smad gene transfer. Vet Ophthalmol 2018; 21(2): 132-9.
[73]
Ratuszny D, Gras C, Bajor A, et al. Mir-145 is a promising therapeutic target to prevent cornea scarring. Hum Gene Ther 2015; 26(10): 698-707.
[74]
Mohan R, Tandon A, Sharma A, Cowden J, Tovey J. Significant inhibition of corneal scarring in vivo with tissue-selective, targeted aav5 decorin gene therapy. Invest Ophthalmol Vis Sci 2011; 52(7): 4833-41.
[75]
Tandon A, Sharma A, Rodier JT, Klibanov AM, Rieger FG, Mohan RR. Bmp7 gene transfer via gold nanoparticles into stroma inhibits corneal fibrosis in vivo. PLoS One 2013; 8(6): e66434.
[76]
Gupta S, Rodier JT, Sharma A, et al. Targeted aav5-smad7 gene therapy inhibits corneal scarring in vivo. PLoS One 2017; 12(3): e0172928.
[77]
Yang JG, Sun NX, Cui LJ, Wang XH, Feng ZH. Adenovirus-mediated delivery of p27(kip1) to prevent wound healing after experimental glaucoma filtration surgery. Acta Pharmacol Sin 2009; 30(4): 413-23.
[78]
Saghizadeh M, Soleymani S, Harounian A, et al. Alterations of epithelial stem cell marker patterns in human diabetic corneas and effects of c-met gene therapy. Mol Vis 2011; 17: 2177-90.
[79]
Saghizadeh M, Kramerov A, Yu F, Castro M, Ljubimov A. Normalization of wound healing and diabetic markers in organ cultured human diabetic corneas by adenoviral delivery of c-met gene. Invest Ophthalmol Vis Sci 2010; 51(4): 1970-80.
[80]
Saghizadeh M, Epifantseva I, Hemmati DM, et al. Enhanced wound healing, kinase and stem cell marker expression in diabetic organ-cultured human corneas upon mmp-10 and cathepsin f gene silencing. Invest Ophthalmol Vis Sci 2013; 54(13): 8172.
[81]
Kramerov AA, Saghizadeh M, Ljubimov AV. Adenoviral gene therapy for diabetic keratopathy: Effects on wound healing and stem cell marker expression in human organ-cultured corneas and limbal epithelial cells. J Vis Exp 2016; 110: e54058.
[82]
Saika S, Ikeda K, Yamanaka O, et al. Therapeutic effects of adenoviral gene transfer of bone morphogenic protein-7 on a corneal alkali injury model in mice. Lab Invest 2005; 85(4): 474-86.
[83]
Gupta S, Fink MK, Ghosh A, et al. Novel combination bmp7 and hgf gene therapy instigates selective myofibroblast apoptosis and reduces corneal haze in vivo. Invest Ophthalmol Vis Sci 2018; 59(2): 1045-57.
[84]
Sam MR, Azadbakhsh AS, Farokhi F, et al. Genetic modification of bone-marrow mesenchymal stem cells and hematopoietic cells with human coagulation factor ix-expressing plasmids. Biologicals 2016; 44(3): 170-7.
[85]
Pittenger MF, Mackay AM, Beck SC, et al. Multilineage potential of adult human mesenchymal stem cells. Science 1999; 284(5411): 143-7.
[86]
Stewart MC, Stewart AA. Mesenchymal stem cells: Characteristics, sources, and mechanisms of action. Vet Clin North Am Equine Pract 2011; 27(2): 243-61.
[87]
Bassi Ê, de Almeida DC, Moraes-Vieira PM, Câmara NO. Exploring the role of soluble factors associated with immune regulatory properties of mesenchymal stem cells. Stem Cell Rev 2012; 8(2): 329-42.
[88]
Marigo I, Dazzi F. The immunomodulatory properties of mesenchymal stem cells. Semin Immunopathol 2011; 33(6): 593-602.
[89]
De Miguel MP, Fuentes-Julian S, Blazquez-Martinez A, et al. Immunosuppressive properties of mesenchymal stem cells: Advances and applications. Curr Mol Med 2012; 12(5): 574-91.
[90]
Gotherstrom C, Ringden O, Tammik C, et al. Immunologic properties of human fetal mesenchymal stem cells. Am J Obstet Gynecol 2004; 190(1): 239-45.
[91]
Aggarwal S, Pittenger MF. Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood 2005; 105(4): 1815-22.
[92]
Duffy MM, Ritter T, Ceredig R, Griffin MD. Mesenchymal stem cell effects on t-cell effector pathways. Stem Cell Res Ther 2011; 2(4): 34.
[93]
Soleymaninejadian E, Pramanik K, Samadian E. Immunomodulatory properties of mesenchymal stem cells: Cytokines and factors. Am J Reprod Immunol 2012; 67(1): 1-8.
[94]
Bassi EJ, de Almeida DC, Moraes-Vieira PM, Camara NO. Exploring the role of soluble factors associated with immune regulatory properties of mesenchymal stem cells. Stem Cell Rev 2012; 8(2): 329-42.
[95]
Bright JJ, Kerr LD, Sriram S. Tgf-beta inhibits il-2-induced tyrosine phosphorylation and activation of jak-1 and stat 5 in t lymphocytes. J Immunol 1997; 159(1): 175-83.
[96]
Lepelletier Y, Lecourt S, Renand A, et al. Galectin-1 and semaphorin-3a are two soluble factors conferring t-cell immunosuppression to bone marrow mesenchymal stem cell. Stem Cells Dev 2010; 19(7): 1075-9.
[97]
Li FR, Wang XG, Deng CY, Qi H, Ren LL, Zhou HX. Immune modulation of co-transplantation mesenchymal stem cells with islet on t and dendritic cells. Clin Exp Immunol 2010; 161(2): 357-63.
[98]
Di G, Du X, Qi X, et al. Mesenchymal stem cells promote diabetic corneal epithelial wound healing through tsg-6-dependent stem cell activation and macrophage switch. Invest Ophthalmol Vis Sci 2017; 58(10): 4344-54.
[99]
Treacy O, O’Flynn L, Ryan AE, et al. Mesenchymal stem cell therapy promotes corneal allograft survival in rats by local and systemic immunomodulation. Am J Transplant 2014; 14(9): 2023-36.
[100]
Sherman AB, Gilger BC, Berglund AK, Schnabel LV. Effect of bone marrow-derived mesenchymal stem cells and stem cell supernatant on equine corneal wound healing in vitro. Stem Cell Res Ther 2017; 8(1): 120.
[101]
Holan V, Trosan P, Cejka C, et al. A comparative study of the therapeutic potential of mesenchymal stem cells and limbal epithelial stem cells for ocular surface reconstruction. Stem Cells Transl Med 2015; 4(9): 1052-63.
[102]
Jia Z, Jiao C, Zhao S, et al. Immunomodulatory effects of mesenchymal stem cells in a rat corneal allograft rejection model. Exp Eye Res 2012; 102: 44-9.
[103]
Veréb Z, Póliska S, Albert R, et al. Role of human corneal stroma-derived mesenchymal-like stem cells in corneal immunity and wound healing. Sci Rep 2016; 6(1): 26227.
[104]
Yun YI, Park SY, Lee HJ, et al. Comparison of the anti-inflammatory effects of induced pluripotent stem cell–derived and bone marrow–derived mesenchymal stromal cells in a murine model of corneal injury. Cytotherapy 2017; 19(1): 28-35.
[105]
Ren G, Zhang L, Zhao X, et al. Mesenchymal stem cell-mediated immunosuppression occurs via concerted action of chemokines and nitric oxide. Cell Stem Cell 2008; 2(2): 141-50.
[106]
François M, Romieu-Mourez R, Li M, Galipeau J. Human msc suppression correlates with cytokine induction of indoleamine 2,3-dioxygenase and bystander m2 macrophage differentiation. Mol Ther 2012; 20(1): 187-95.
[107]
Duijvestein M, Wildenberg ME, Welling MM, et al. Pretreatment with interferon-γ enhances the therapeutic activity of mesenchymal stromal cells in animal models of colitis. Stem Cells 2011; 29(10): 1549-58.
[108]
Ren G, Zhao X, Zhang L, et al. Inflammatory cytokine-induced intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in mesenchymal stem cells are critical for immunosuppression. J Immunol 2010; 184(5): 2321-8.
[109]
Ren G, Su J, Zhang L, et al. Species variation in the mechanisms of mesenchymal stem cell-mediated immunosuppression. Stem Cells 2009; 27(8): 1954-62.
[110]
Kobolak J, Dinnyes A, Memic A, Khademhosseini A, Mobasheri A. Mesenchymal stem cells: Identification, phenotypic characterization, biological properties and potential for regenerative medicine through biomaterial micro-engineering of their niche. Methods 2016; 99: 62-8.
[111]
Shohara R, Yamamoto A, Takikawa S, et al. Mesenchymal stromal cells of human umbilical cord wharton’s jelly accelerate wound healing by paracrine mechanisms. Cytotherapy 2012; 14(10): 1171-81.
[112]
Cejka C, Holan V, Trosan P, Zajicova A, Javorkova E, Cejkova J. The favorable effect of mesenchymal stem cell treatment on the antioxidant protective mechanism in the corneal epithelium and renewal of corneal optical properties changed after alkali burns. Oxid Med Cell Longev 2016; 2016: 5843809.
[113]
Almaliotis D, Koliakos G, Papakonstantinou E, et al. Mesenchymal stem cells improve healing of the cornea after alkali injury. Graefes Arch Clin Exp Ophthalmol 2015; 253(7): 1121-35.
[114]
Oh J, Kim M, Shin M, et al. The anti-inflammatory and anti-angiogenic role of mesenchymal stem cells in corneal wound healing following chemical injury. Stem Cells 2008; 26(4): 1047-55.
[115]
Chavakis E, Urbich C, Dimmeler S. Homing and engraftment of progenitor cells: A prerequisite for cell therapy. J Mol Cell Cardiol 2008; 45(4): 514-22.
[116]
Wu Y, Zhao R. The role of chemokines in mesenchymal stem cell homing to myocardium. Stem Cell Rev 2012; 8(1): 243-50.
[117]
Wang G, Zhang Q, Zhuo Z, et al. Enhanced homing of cxcr-4 modified bone marrow-derived mesenchymal stem cells to acute kidney injury tissues by micro-bubble-mediated ultrasound exposure. Ultrasound Med Biol 2016; 42(2): 539-48.
[118]
Cashman TJ, Gouon-Evans V, Costa KD. Mesenchymal stem cells for cardiac therapy: Practical challenges and potential mechanisms. Stem Cell Rev 2013; 9(3): 254-65.
[119]
Song HB, Park SY, Ko JH, et al. Mesenchymal stromal cells inhibit inflammatory lymphangiogenesis in the cornea by suppressing macrophage in a tsg-6-dependent manner. Mol Ther 2018; 26(1): 162-72.
[120]
Oh JY, Kim MK, Shin MS, et al. The anti-inflammatory and anti-angiogenic role of mesenchymal stem cells in corneal wound healing following chemical injury. Stem Cells 2008; 26(4): 1047-55.
[121]
Cejkova J, Stipek S, Crkovska J, Ardan T, Midelfart A. Reactive oxygen species (ros)-generating oxidases in the normal rabbit cornea and their involvement in the corneal damage evoked by uvb rays. Histol Histopathol 2001; 16(2): 523-33.
[122]
Finkel T, Holbrook NJ. Oxidants, oxidative stress and the biology of ageing. Nature 2000; 408(6809): 239-47.
[123]
Kemp K, Gray E, Mallam E, Scolding N, Wilkins A. Inflammatory cytokine induced regulation of superoxide dismutase 3 expression by human mesenchymal stem cells. Stem Cell Rev 2010; 6(4): 548-59.
[124]
Kemp K, Hares K, Mallam E, Heesom KJ, Scolding N, Wilkins A. Mesenchymal stem cell-secreted superoxide dismutase promotes cerebellar neuronal survival. J Neurochem 2010; 114(6): 1569-80.
[125]
Jiang D, Gao F, Zhang Y, et al. Mitochondrial transfer of mesenchymal stem cells effectively protects corneal epithelial cells from mitochondrial damage. Cell Death Dis 2016; 7(11): e2467.
[126]
Ahmad T, Mukherjee S, Pattnaik B, et al. Miro1 regulates intercellular mitochondrial transport & enhances mesenchymal stem cell rescue efficacy. EMBO J 2014; 33(9): 994-1010.
[127]
Lan Y, Kodati S, Lee HS, Omoto M, Jin Y, Chauhan SK. Kinetics and function of mesenchymal stem cells in corneal injury. Invest Ophthalmol Vis Sci 2012; 53(7): 3638-44.
[128]
Jiang Z, Liu G, Meng F, et al. Paracrine effects of mesenchymal stem cells on the activation of keratocytes. Br J Ophthalmol 2017; 101(11): 1583-90.
[129]
Eslani M, Putra I, Shen X, et al. Corneal mesenchymal stromal cells are directly antiangiogenic via pedf and sflt-1. Invest Ophthalmol Vis Sci 2017; 58(12): 5507-17.
[130]
Pinarli FA, Okten G, Beden U, et al. Keratinocyte growth factor-2 and autologous serum potentiate the regenerative effect of mesenchymal stem cells in cornea damage in rats. Int J Ophthalmol 2014; 7(2): 211-9.
[131]
Demirayak B, Yüksel N, Çelik OS, et al. Effect of bone marrow and adipose tissue-derived mesenchymal stem cells on the natural course of corneal scarring after penetrating injury. Exp Eye Res 2016; 151: 227-35.
[132]
Ko JH, Lee HJ, Jeong HJ, et al. Mesenchymal stem/stromal cells precondition lung monocytes/macrophages to produce tolerance against allo- and autoimmunity in the eye. Proc Natl Acad Sci USA 2016; 113(1): 158-63.
[133]
Jia Z, Jiao C, Zhao S, et al. Immunomodulatory effects of mesenchymal stem cells in a rat corneal allograft rejection model. Exp Eye Res 2012; 102: 44-9.
[134]
Treacy O, O’Flynn L, Ryan AE, et al. Mesenchymal stem cell therapy promotes corneal allograft survival in rats by local and systemic immunomodulation. Am J Transplant 2014; 14(9): 2023-36.
[135]
Omoto M, Katikireddy KR, Rezazadeh A, Dohlman TH, Chauhan SK. Mesenchymal stem cells home to inflamed ocular surface and suppress allosensitization in corneal transplantation. Invest Ophthalmol Vis Sci 2014; 55(10): 6631-8.
[136]
Fuentes-Julian S, Arnalich-Montiel F, Jaumandreu L, et al. Adipose-derived mesenchymal stem cell administration does not improve corneal graft survival outcome. PLoS One 2015; 10(3): e0117945.
[137]
Wagner J, Kean T, Young R, Dennis JE, Caplan AI. Optimizing mesenchymal stem cell-based therapeutics. Curr Opin Biotechnol 2009; 20(5): 531-6.
[138]
Karp JM, Leng Teo GS. Mesenchymal stem cell homing: The devil is in the details. Cell Stem Cell 2009; 4(3): 206-16.
[139]
Kang SK, Shin IS, Ko MS, Jo JY, Ra JC. Journey of mesenchymal stem cells for homing: Strategies to enhance efficacy and safety of stem cell therapy. Stem Cells Int 2012; 2012: 342968.
[140]
Zhang X, Huang W, Chen X, et al. Cxcr5-overexpressing mesenchymal stromal cells exhibit enhanced homing and can decrease contact hypersensitivity. Mol Ther 2017; 25(6): 1434-47.
[141]
Liu H, Liu S, Li Y, et al. The role of sdf-1-cxcr4/cxcr7 axis in the therapeutic effects of hypoxia-preconditioned mesenchymal stem cells for renal ischemia/reperfusion injury. PLoS One 2012; 7(4): e34608.
[142]
Guan M, Yao W, Liu R, et al. Directing mesenchymal stem cells to bone to augment bone formation and increase bone mass. Nat Med 2012; 18(3): 456-62.
[143]
Chen W, Li M, Cheng H, et al. Overexpression of the mesenchymal stem cell cxcr4 gene in irradiated mice increases the homing capacity of these cells. Cell Biochem Biophys 2013; 67(3): 1181-91.
[144]
Li H, Jiang Y, Jiang X, et al. Ccr7 guides migration of mesenchymal stem cell to secondary lymphoid organs: A novel approach to separate gvhd from gvl effect. Stem Cells 2014; 32(7): 1890-903.
[145]
Ma XW, Cui DP, Zhao DW. Vascular endothelial growth factor/bone morphogenetic protein-2 bone marrow combined modification of the mesenchymal stem cells to repair the avascular necrosis of the femoral head. Int J Clin Exp Med 2015; 8(9): 15528-34.
[146]
Li J, Zheng C-Q, Li Y, Yang C, Lin H, Duan H-G. Hepatocyte growth factor gene-modified mesenchymal stem cells augment sinonasal wound healing. Stem Cells Dev 2015; 24(15): 1817-30.
[147]
Guo H, Zhao N, Gao H, He X. Mesenchymal stem cells overexpressing interleukin-35 propagate immunosuppressive effects in mice. Scand J Immunol 2017; 86(5): 389-95.
[148]
Li Q, Han SM, Song WJ, Park SC, Ryu MO, Youn HY. Anti-inflammatory effects of oct4/sox2-overexpressing human adipose tissue-derived mesenchymal stem cells. In Vivo 2017; 31(3): 349-56.
[149]
Hu Y, Zhang Y, Tian K, Xun C, Wang S, Lv D. Effects of nerve growth factor and basic fibroblast growth factor dual gene modification on rat bone marrow mesenchymal stem cell differentiation into neuron-like cells in vitro. Mol Med Rep 2016; 13(1): 49-58.

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy