608
Views
14
CrossRef citations to date
0
Altmetric
Mini-Review

Development of Causative Treatment Strategies for Lacrimal Gland Insufficiency by Tissue Engineering and Cell Therapy. Part 1: Regeneration of Lacrimal Gland Tissue: Can We Stimulate Lacrimal Gland Renewal In Vivo?

, , , , &
Pages 1131-1142 | Received 13 Oct 2015, Accepted 28 Jan 2016, Published online: 26 Apr 2016

References

  • Lang GK. Augenheilkunde. Stuttgart: Georg Thieme Verlag; 2014.
  • Venable JH, Grafflin AL. Gross anatomy of the orbital glands in the albino rat. J Mammal 1940;21(1):66–71.
  • Kanski J. Klinische ophtalmologie. Lehrbuch und atlas. München: Elsevier GmbH; 2008.
  • Sachsenweger M. Duale Reihe Augenheilkunde. Stuttgart: Georg Thieme Verlag; 2003.
  • Janssen P, Van Bijsterveld O. Comparison of electrophoretic techniques for the analysis of human tear fluid proteins. Clin Chim Acta 1981;114(2):207–218.
  • Zhou L, Beuerman RW, Foo Y, Liu S, Ang LP, Tan DT. Characterisation of human tear proteins using high-resolution mass spectrometry. Ann Acad Med Singapore 2006;35(6):400.
  • Scott BL, Pease DC. Electron microscopy of the salivary and lacrimal glands of the rat. Am J Anat 1959;104(1):115–161.
  • Dartt DA. Neural regulation of lacrimal gland secretory processes: relevance in dry eye diseases. Prog Retin Eye Res 2009;28(3):155–177.
  • Gipson IK, Joyce NC, Zieske JD. The anatomy and cell biology of the human cornea, limbus, conjucitva and adnexa. In Foster SC, Azar DT, Dohlman CH (Eds). Smolin and Thoft’s The Cornea: Scientific Foundations and Clinical Practice. 4th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2005.
  • Rocha EM, Alves M, Rios JD, Dartt DA. The aging lacrimal gland: changes in structure and function. Ocul Surf 2008;6(4):162–174.
  • Lemp MA, Foulks GN. The definition and classification of dry eye disease. Ocul Surf 2007;5(2):75–92.
  • Pflugfelder SC, Stern ME. Dry eye: inflammation of the lacrimal functional unit. In Pleyer U, Mondino B (Eds). Uvetitis and Immunological Disorders. Berlin, Germany: Springer; 2005.
  • Williamson J, Gibson A, Wilson T, Forrester J, Whaley K, Dick W. Histology of the lacrimal gland in keratoconjunctivitis sicca. Br J Ophthalmol 1973;57(11):852.
  • Matsumoto I, Tsubota K, Satake Y, Kita Y, Matsumura R, Murata H, et al. Common T cell receptor clonotype in lacrimal glands and labial salivary glands from patients with Sjögren’s syndrome. J Clin Invest 1996;97(8):1969.
  • Saito I, Terauchi K, Shimuta M, Nishiimura S, Yoshino K, Takeuchi T, et al. Expression of cell adhesion molecules in the salivary and lacrimal glands of Sjogren’s syndrome. J Clin Lab Anal 1993;7(3):180–187.
  • Stern ME, Gao J, Schwalb TA, Ngo M, Tieu DD, Chan C-C, et al. Conjunctival T-cell subpopulations in Sjögren’s and non-Sjögren’s patients with dry eye. Invest Ophthalmol Vis Sci 2002;43(8):2609–2614.
  • Kunert KS, Tisdale AS, Stern ME, Smith J, Gipson IK. Analysis of topical cyclosporine treatment of patients with dry eye syndrome: effect on conjunctival lymphocytes. Arch Ophthalmol 2000;118(11):1489–1496.
  • Solomon A, Dursun D, Liu Z, Xie Y, Macri A, Pflugfelder SC. Pro-and anti-inflammatory forms of interleukin-1 in the tear fluid and conjunctiva of patients with dry-eye disease. Invest Ophthalmol Vis Sci 2001;42(10):2283–2292.
  • Nakamura S, Kinoshita S, Yokoi N, Ogawa Y, Shibuya M, Nakashima H, et al. Lacrimal hypofunction as a new mechanism of dry eye in visual display terminal users. PLoS One 2010;5(6):e11119.
  • Xiao B, Wang Y, Reinach PS, Ren Y, Li J, Hua S, et al. Dynamic ocular surface and lacrimal gland changes induced in experimental murine dry eye. PLoS One 2015;10(1):e0115333.
  • Hessen M, Akpek EK. Dry eye: an inflammatory ocular disease. J Ophthalmic Vis Res 2014;9(2):240–250.
  • Borrelli M, Schroder C, Dart JK, Collin JR, Sieg P, Cree IA, et al. Long-term follow-up after submandibular gland transplantation in severe dry eyes secondary to cicatrizing conjunctivitis. Am J Ophthalmol 2010;150(6):894–904.
  • Qin J, Zhang L, Cai ZG, Mao C, Liu XJ, Lv L, et al. Microvascular autologous transplantation of partial submandibular gland for severe keratoconjunctivitis sicca. Br J Ophthalmol 2013;97(9):1123–1128.
  • Schroder C, Sieg P, Framme C, Honnicke K, Hakim SG, Geerling G. Transplantation of the submandibular gland in absolute dry eyes. Effect on the ocular surface. Klin Monbl Augenheilkd 2002;219(7):494–501.
  • Sieg P, Geerling G, Kosmehl H, Lauer I, Warnecke K, von Domarus H. Microvascular submandibular gland transfer for severe cases of keratoconjunctivitis sicca. Plas Reconstr Surg 2000;106(3):554–560.
  • Henker R, Scholz M, Gaffling S, Asano N, Hampel U, Garreis F, et al. Morphological features of the porcine lacrimal gland and its compatibility for human lacrimal gland xenografting. PLoS One 2013;8(9):e74046.
  • Samy KP, Martin BM, Turgeon NA, Kirk AD. Islet cell xenotransplantation: a serious look toward the clinic. Xenotransplantation 2014;21(3):221–229.
  • Choi HJ, Kim MK, Lee HJ, Ko JH, Jeong SH, Lee JI, et al. Efficacy of pig-to-rhesus lamellar corneal xenotransplantation. Invest Ophthalmol Vis Sci 2011;52(9):6643–6650.
  • Lehmann S, Walther T, Kempfert J, Leontjev S, Rastan A, Falk V, et al. Stentless versus conventional xenograft aortic valve replacement: midterm results of a prospectively randomized trial. Ann Thorac Surg 2007;84(2):467–472.
  • Kimsa-Dudek M, Strzalka-Mrozik B, Kimsa MW, Blecharz I, Gola J, Skowronek B, et al. Screening pigs for xenotransplantation: expression of porcine endogenous retroviruses in transgenic pig skin. Transgenic Res 2015;24(3):529–536.
  • The epidemiology of dry eye disease: report of the Epidemiology Subcommittee of the International Dry Eye WorkShop (2007). Ocular Surf 2007;5(2):93–107.
  • Avni I, Garzozi HJ, Barequet IS, Segev F, Varssano D, Sartani G, et al. Treatment of dry eye syndrome with orally administered CF101: data from a phase 2 clinical trial. Ophthalmology 2010;117(7):1287–1293.
  • Kawashima M, Kawakita T, Inaba T, Okada N, Ito M, Shimmura S, et al. Dietary lactoferrin alleviates age-related lacrimal gland dysfunction in mice. PLoS One 2012;7(3):e33148.
  • Shigeyasu C, Yamada M, Akune Y, Tsubota K. Diquafosol sodium ophthalmic solution for the treatment of dry eye: clinical evaluation and biochemical analysis of tear composition. Jpn J Ophthalmol 2015;59(6):415–420.
  • Vijmasi T, Chen FY, Balasubbu S, Gallup M, McKown RL, Laurie GW, et al. Topical administration of lacritin is a novel therapy for aqueous-deficient dry eye disease. Invest Ophthalmol Vis Sci 2014;55(8):5401–5409.
  • Wang W, Jashnani A, Aluri SR, Gustafson JA, Hsueh PY, Yarber F, et al. A thermo-responsive protein treatment for dry eyes. J Control Release 2015;199:156–167.
  • Kawakita T, Shimmura S, Tsubota K. Effect of oral pilocarpine in treating severe dry eye in patients with sjogren syndrome. Asia Pac J Ophthalmol 2015;4(2):101–105.
  • Papas AS, Sherrer YS, Charney M, Golden HE, Medsger TA, Jr., Walsh BT, et al. Successful treatment of dry mouth and dry eye symptoms in sjogren’s syndrome patients with oral pilocarpine: a randomized, placebo-controlled, dose-adjustment study. J Clin Rheumatol 2004;10(4):169–177.
  • Avila MY. Restoration of human lacrimal function following platelet-rich plasma injection. Cornea 2014;33(1):18–21.
  • Ross J, Gherardi E, Mallorqui-Fernandez N, Bocci M, Sobkowicz A, Rees M, et al. Protein engineered variants of hepatocyte growth factor/scatter factor promote proliferation of primary human hepatocytes and in rodent liver. Gastroenterology 2012;142(4):897–906.
  • Riley KG, Pasek RC, Maulis MF, Peek J, Thorel F, Brigstock DR, et al. Connective tissue growth factor modulates adult beta-cell maturity and proliferation to promote beta-cell regeneration in mice. Diabetes 2015;64(4):1284–1298.
  • Lee MJ, Kim DH, Ryu JS, Ko AY, Ko JH, Kim MK, et al. Topical TSG-6 administration protects the ocular surface in two mouse models of inflammation-related dry eye. Invest Ophthalmol Vis Sci 2015;56(9):5175–5181.
  • Kato T, Okumi M, Tanemura M, Yazawa K, Kakuta Y, Yamanaka K, et al. Adipose tissue-derived stem cells suppress acute cellular rejection by TSG-6 and CD44 interaction in rat kidney transplantation. Transplantation 2014;98(3):277–284.
  • Qi Y, Jiang D, Sindrilaru A, Stegemann A, Schatz S, Treiber N, et al. TSG-6 released from intradermally injected mesenchymal stem cells accelerates wound healing and reduces tissue fibrosis in murine full-thickness skin wounds. J Invest Dermatol 2014;134(2):526–537.
  • Wang S, Lee JS, Hyun J, Kim J, Kim SU, Cha HJ, et al. Tumor necrosis factor-inducible gene 6 promotes liver regeneration in mice with acute liver injury. Stem Cell Res Ther 2015;6:20.
  • Oh JY, Roddy GW, Choi H, Lee RH, Ylostalo JH, Rosa RH, Jr., et al. Anti-inflammatory protein TSG-6 reduces inflammatory damage to the cornea following chemical and mechanical injury. Proc Natl Acad Sci USA 2010;107(39):16875–16880.
  • Barabino S, Dana MR. Animal models of dry eye: a critical assessment of opportunities and limitations. Invest Ophthalmol Vis Sci 2004;45(6):1641–1646.
  • Beyazyildiz E, Pinarli FA, Beyazyildiz O, Hekimoglu ER, Acar U, Demir MN, et al. Efficacy of topical mesenchymal stem cell therapy in the treatment of experimental dry eye syndrome model. Stem Cells Int 2014;2014:250230.
  • Lee MJ, Ko AY, Ko JH, Lee HJ, Kim MK, Wee WR, et al. Mesenchymal stem/stromal cells protect the ocular surface by suppressing inflammation in an experimental dry eye. Mol Ther 2015;23(1):139–146.
  • Park SA, Reilly CM, Wood JA, Chung DJ, Carrade DD, Deremer SL, et al. Safety and immunomodulatory effects of allogeneic canine adipose-derived mesenchymal stromal cells transplanted into the region of the lacrimal gland, the gland of the third eyelid and the knee joint. Cytotherapy 2013;15(12):1498–1510.
  • Villatoro AJ, Fernandez V, Claros S, Rico-Llanos GA, Becerra J, Andrades JA. Use of adipose-derived mesenchymal stem cells in keratoconjunctivitis sicca in a canine model. Biomed Res Int 2015;2015:527926.
  • Weng J, He C, Lai P, Luo C, Guo R, Wu S, et al. Mesenchymal stromal cells treatment attenuates dry eye in patients with chronic graft-versus-host disease. Mol Ther 2012;20(12):2347–2354.
  • Wood JA, Chung DJ, Park SA, Zwingenberger AL, Reilly CM, Ly I, et al. Periocular and intra-articular injection of canine adipose-derived mesenchymal stem cells: an in vivo imaging and migration study. J Ocul Pharmacol Ther 2012;28(3):307–317.
  • Karaoz E, Ayhan S, Gacar G, Aksoy A, Duruksu G, Okçu A, et al. Isolation and characterization of stem cells from pancreatic islet: pluripotency, differentiation potential and ultrastructural characteristics. Cytotherapy 2010;12(3):288–302.
  • Shatos MA, Haugaard-Kedstrom L, Hodges RR, Dartt DA. Isolation and characterization of progenitor cells in uninjured, adult rat lacrimal gland. Invest Ophthalmol Vis Sci 2012;53(6):2749–2759.
  • Zhang L, Hong T-P, Hu J, Liu Y-N, Wu Y-H, Li L-S. Nestin-positive progenitor cells isolated from human fetal pancreas have phenotypic markers identical to mesenchymal stem cells. World J Gastroenterol 2005;11(19):2906–2911.
  • Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 2006;8(4):315–317.
  • Friedenstein A, Piatetzky-Shapiro I, Petrakova K. Osteogenesis in transplants of bone marrow cells. J Embryol Exp Morphol 1966;16(3):381–390.
  • Owen M, Friedenstein A. Stromal stem cells: marrow-derived osteogenic precursors. Ciba Found Symp 1988;136:42–60.
  • Jeong J, Baek H, Kim Y-J, Choi Y, Lee H, Lee E, et al. Human salivary gland stem cells ameliorate hyposalivation of radiation-damaged rat salivary glands. Exp Mol Med 2013;45(11):e58.
  • Kern S, Eichler H, Stoeve J, Klüter H, Bieback K. Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue. Stem Cells 2006;24(5):1294–1301.
  • Zuk PA, Zhu M, Ashjian P, De Ugarte DA, Huang JI, Mizuno H, et al. Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell 2002;13(12):4279–4295.
  • Carlotti F, Zaldumbide A, Loomans CJ, van Rossenberg E, Engelse M, de Koning EJ, et al. Isolated human islets contain a distinct population of mesenchymal stem cells. Islets 2010;2(3):164–173.
  • Davani B, Ikonomou L, Raaka BM, Geras‐Raaka E, Morton RA, Marcus‐Samuels B, et al. Human islet‐derived precursor cells are mesenchymal stromal cells that differentiate and mature to hormone‐expressing cells in vivo. Stem Cells 2007;25(12):3215–3222.
  • Eberhardt M, Salmon P, von Mach M-A, Hengstler JG, Brulport M, Linscheid P, et al. Multipotential nestin and Isl-1 positive mesenchymal stem cells isolated from human pancreatic islets. Biochem Biophys Res Commun 2006;345(3):1167–1176.
  • Gallo R, Gambelli F, Gava B, Sasdelli F, Tellone V, Masini M, et al. Generation and expansion of multipotent mesenchymal progenitor cells from cultured human pancreatic islets. Cell Death Differ 2007;14(11):1860–1871.
  • Hu Y, Liao L, Wang Q, Ma L, Ma G, Jiang X, et al. Isolation and identification of mesenchymal stem cells from human fetal pancreas. J Lab Clin Med 2003;141(5):342–349.
  • Seeberger KL, Dufour JM, Shapiro AMJ, Lakey JR, Rajotte RV, Korbutt GS. Expansion of mesenchymal stem cells from human pancreatic ductal epithelium. Lab Invest 2006;86(2):141–153.
  • Sun S, Guo Z, Xiao X, Liu B, Liu X, Tang PH, et al. Isolation of mouse marrow mesenchymal progenitors by a novel and reliable method. Stem Cells 2003;21(5):527–535.
  • Bifari F, Lisi V, Mimiola E, Pasini A, Krampera M. Immune modulation by mesenchymal stem cells. Transfus Med Hemother 2008;35(3):194–204.
  • Cselenyak A, Pankotai E, Horvath EM, Kiss L, Lacza Z. Mesenchymal stem cells rescue cardiomyoblasts from cell death in an in vitro ischemia model via direct cell-to-cell connections. BMC Cell Biol 2010;11:29.
  • Kim SY, Lee JH, Kim HJ, Park MK, Huh JW, Ro JY, et al. Mesenchymal stem cell-conditioned media recovers lung fibroblasts from cigarette smoke-induced damage. Am J Physiol Lung Cell Mol Physiol 2012;302(9):L891–L908.
  • Okumura K, Nakamura K, Hisatomi Y, Nagano K, Tanaka Y, Terada K, et al. Salivary gland progenitor cells induced by duct ligation differentiate into hepatic and pancreatic lineages. Hepatology 2003;38(1):104–113.
  • Oertel M, Shafritz DA. Stem cells, cell transplantation and liver repopulation. Biochim Biophys Acta 2008;1782(2):61–74.
  • Bird TG, Lorenzini S, Forbes SJ. Activation of stem cells in hepatic diseases. Cell Tiss Res 2008;331(1):283–300.
  • Kishi T, Takao T, Fujita K, Taniguchi H. Clonal proliferation of multipotent stem/progenitor cells in the neonatal and adult salivary glands. Biochem Biophys Res Commun 2006;340(2):544–552.
  • Lim JY, Yi T, Lee S, Kim J, Kim SN, Song SU, et al. Establishment and characterization of mesenchymal stem cell-like clonal stem cells from mouse salivary glands. Tissue Eng Part C 2014;21(5):447–457.
  • Lombaert IM, Brunsting JF, Wierenga PK, Faber H, Stokman MA, Kok T, et al. Rescue of salivary gland function after stem cell transplantation in irradiated glands. PLoS One 2008;3(4):e2063.
  • Man YG, Ball WD, Marchetti L, Hand AR. Contributions of intercalated duct cells to the normal parenchyma of submandibular glands of adult rats. Anat Rec 2001;263(2):202–214.
  • Feng J, van der Zwaag M, Stokman MA, van Os R, Coppes RP. Isolation and characterization of human salivary gland cells for stem cell transplantation to reduce radiation-induced hyposalivation. Radiother Oncol 2009;92(3):466–471.
  • Zoukhri D, Macari E, Kublin CL. A single injection of interleukin-1 induces reversible aqueous-tear deficiency, lacrimal gland inflammation, and acinar and ductal cell proliferation. Exp Eye Res 2007;84(5):894–904.
  • You S, Kublin CL, Avidan O, Miyasaki D, Zoukhri D. Isolation and propagation of mesenchymal stem cells from the lacrimal gland. Invest Ophthalmol Vis Sci 2011;52(5):2087–2094.
  • Zoukhri D, Fix A, Alroy J, Kublin CL. Mechanisms of murine lacrimal gland repair after experimentally induced inflammation. Invest Ophthalmol Vis Sci 2008;49(10):4399–4406.
  • Ackermann P, Hetz S, Dieckow J, Schicht M, Richter A, Kruse C, et al. Isolation and investigation of presumptive murine lacrimal gland stem cells. Invest Ophthalmol Vis Sci 2015;56(8):4350–4363.
  • Tiwari S, Ali MJ, Balla MM, Naik MN, Honavar SG, Reddy VAP, et al. Establishing human lacrimal gland cultures with secretory function. PLoS One 2012;7(1):e29458.
  • Baddoo M, Hill K, Wilkinson R, Gaupp D, Hughes C, Kopen GC, et al. Characterization of mesenchymal stem cells isolated from murine bone marrow by negative selection. J Cell Biochem 2003;89(6):1235–1249.
  • Hachisuka H, Mochizuki Y, Yasunaga Y, Natsu K, Sharman P, Shinomiya R, et al. Flow cytometric discrimination of mesenchymal progenitor cells from bone marrow-adherent cell populations using CD34/44/45 (-) and Sca-1 (+) markers. J Orthop Sci 2007;12(2):161–169.
  • Harting M, Jimenez F, Pati S, Baumgartner J, Cox C. Immunophenotype characterization of rat mesenchymal stromal cells. Cytotherapy 2008;10(3):243–253.
  • Lamoury F, Croitoru-Lamoury J, Brew B. Undifferentiated mouse mesenchymal stem cells spontaneously express neural and stem cell markers Oct-4 and Rex-1. Cytotherapy 2006;8(3):228–242.
  • Meirelles LDS, Nardi NB. Murine marrow‐derived mesenchymal stem cell: isolation, in vitro expansion, and characterization. Br J Haematol 2003;123(4):702–711.
  • Rivkin R, Ben-Ari A, Kassis I, Zangi L, Gaberman E, Levdansky L, et al. High-yield isolation, expansion, and differentiation of murine bone marrow-derived mesenchymal stem cells using fibrin microbeads (FMB). Cloning Stem Cells 2007;9(2):157–175.
  • Schrepfer S, Deuse T, Lange C, Katzenberg R, Reichenspurner H, Robbins RC, et al. Simplified protocol to isolate, purify, and culture expand mesenchymal stem cells. Stem Cells Dev 2007;16(1):105–108.
  • Tropel P, Noel D, Platet N, Legrand P, Benabid A-L, Berger F. Isolation and characterisation of mesenchymal stem cells from adult mouse bone marrow. Exp Cell Res 2004;295(2):395–406.
  • Roth M, Spaniol K, Kordes C, Schwarz S, Mertsch S, Haussinger D, et al. The influence of oxygen on the proliferative capacity and differentiation potential of lacrimal gland-derived mesenchymal stem cells. Invest Ophthalmol Vis Sci 2015;56(8):4741–4752.
  • Sung J, Yang H-M, Park J, Choi G-S, Joh J-W, Kwon C, et al., editors. Isolation and characterization of mouse mesenchymal stem cells. Transplant Proc 2008;40(8):2649–2654.
  • Mafi P, Hindocha S, Mafi R, Griffin M, Khan W. Adult mesenchymal stem cells and cell surface characterization-a systematic review of the literature. Open Orthop J 2011;5(Suppl.2):253–260.
  • Limbert C, Ebert R, Schilling T, Path G, Benisch P, Klein-Hitpass L, et al. Functional signature of human islet-derived precursor cells compared to bone marrow-derived mesenchymal stem cells. Stem Cells Dev 2009;19(5):679–691.
  • Caplan AI, Dennis JE. Mesenchymal stem cells as trophic mediators. J Cell Biochem 2006;98(5):1076–1084.
  • Chen L, Tredget EE, Wu PY, Wu Y. Paracrine factors of mesenchymal stem cells recruit macrophages and endothelial lineage cells and enhance wound healing. PLoS One 2008;3(4):e1886.
  • Akram KM, Samad S, Spiteri MA, Forsyth NR. Mesenchymal stem cells promote alveolar epithelial cell wound repair in vitro through distinct migratory and paracrine mechanisms. Resp Res 2013;14:9.
  • Hu N, Zhang YY, Gu HW, Guan HJ. Effects of bone marrow mesenchymal stem cells on cell proliferation and growth factor expression of limbal epithelial cells in vitro. Ophthal Res 2012;48(2):82–88.
  • Moghadasali R, Mutsaers HA, Azarnia M, Aghdami N, Baharvand H, Torensma R, et al. Mesenchymal stem cell-conditioned medium accelerates regeneration of human renal proximal tubule epithelial cells after gentamicin toxicity. Exp Toxicol Pathol 2013;65(5):595–600.
  • Walter MN, Wright KT, Fuller HR, MacNeil S, Johnson WE. Mesenchymal stem cell-conditioned medium accelerates skin wound healing: an in vitro study of fibroblast and keratinocyte scratch assays. Exp Cell Res 2010;316(7):1271–1281.
  • Khalili S, Liu Y, Kornete M, Roescher N, Kodama S, Peterson A, et al. Mesenchymal stromal cells improve salivary function and reduce lymphocytic infiltrates in mice with Sjogren’s-like disease. PLoS One 2012;7(6):e38615.
  • Lim J-Y, Yi T, Choi J-S, Jang YH, Lee S, Kim HJ, et al. Intraglandular transplantation of bone marrow-derived clonal mesenchymal stem cells for amelioration of post-irradiation salivary gland damage. Oral Onc 2013;49(2):136–143.
  • Xiong X, Shi X, Chen F. Human adipose tissue-derived stem cells alleviate radiation-induced xerostomia. Int J Mol Med 2014;34(3):749–755.
  • Xu J, Wang D, Liu D, Fan Z, Zhang H, Liu O, et al. Allogeneic mesenchymal stem cell treatment alleviates experimental and clinical Sjögren syndrome. Blood 2012;120(15):3142–3151.
  • Zhang NN, Huang GL, Han QB, Hu X, Yi J, Yao L, et al. Functional regeneration of irradiated salivary glands with human amniotic epithelial cells transplantation. Int J Clin Exp Pathol 2013;6(10):2039–2047.
  • Huang GL, Zhang NN, Wang JS, Yao L, Zhao YJ, Wang YY. Transdifferentiation of human amniotic epithelial cells into acinar cells using a double-chamber system. Cell Reprogram 2012;14(4):377–383.
  • Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 2006;126(4):663–676.
  • Zhang Y, Deng C, Qian J, Zhang M, Li X. Improvement of radiotherapy-induced lacrimal gland injury by induced pluripotent stem cell-derived conditioned medium via MDK and inhibition of the p38/JNK pathway. Int J Mol Sci 2014;15(10):18407–18421.
  • Frenette PS, Pinho S, Lucas D, Scheiermann C. Mesenchymal stem cell: keystone of the hematopoietic stem cell niche and a stepping-stone for regenerative medicine. Annu Rev Immunol 2013;31:285–316.
  • Yin H, Kanasty RL, Eltoukhy AA, Vegas AJ, Dorkin JR, Anderson DG. Non-viral vectors for gene-based therapy. Nat Rev Genet 2014;15(8):541–555.
  • Selvam S, Thomas PB, Hamm-Alvarez SF, Schechter JE, Stevenson D, Mircheff AK, et al. Current status of gene delivery and gene therapy in lacrimal gland using viral vectors. Adv Drug Del Rev 2006;58(11):1243–1257.
  • Rocha EM, Di Pasquale G, Riveros PP, Quinn K, Handelman B, Chiorini JA. Transduction, tropism, and biodistribution of AAV vectors in the lacrimal gland. Invest Ophthalmol Vis Sci 2011;52(13):9567–9572.
  • Trousdale MD, Zhu Z, Stevenson D, Schechter JE, Ritter T, Mircheff AK. Expression of TNF inhibitor gene in the lacrimal gland promotes recovery of tear production and tear stability and reduced immunopathology in rabbits with induced autoimmune dacryoadenitis. J Autoimmune Dis 2005;2:6.
  • Thomas PB, Samant DM, Selvam S, Wei RH, Wang Y, Stevenson D, et al. Adeno-associated virus-mediated IL-10 gene transfer suppresses lacrimal gland immunopathology in a rabbit model of autoimmune dacryoadenitis. Invest Ophthalmol Vis Sci 2010;51(10):5137–5144.
  • Yoo C, Vines JB, Alexander G, Murdock K, Hwang P, Jun H-W. Adult stem cells and tissue engineering strategies for salivary gland regeneration: a review. Biomater Res 2014;18(1):9.
  • Xu J, Wang D, Liu D, Fan Z, Zhang H, Liu O, et al. Allogeneic mesenchymal stem cell treatment alleviates experimental and clinical Sjogren syndrome. Blood 2012;120(15):3142–3151.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.