Extracellular matrix plays an important role in stem cell niche which maintains the undifferentiated stem cell phenotype. Human corneal epithelial stem cells are presumed to reside mainly at the limbal basal epithelium. Efforts have been made to characterize different components of the extracellular matrix that are preferentially expressed at the limbus. Mounting evidence from experimental data suggest that these components are part of the stem cell niche and play a role in the homeostasis of limbal stem cells. The extracellular matrix provides a mechanical and structural support as well as regulates cellular functions such as adhesion, migration, proliferation, self-renewal and differentiation. Optimization of the extracellular matrix components might be able to recreate an ex vivo stem cell niche to expand limbal stem cells.
References
[1]
Majo, F.; Rochat, A.; Nicolas, M.; Jaoude, G.A.; Barrandon, Y. Oligopotent stem cells are distributed throughout the mammalian ocular surface. Nature 2008, 456, 250–254.
[2]
Ricard-Blum, S. The collagen family. Cold Spring Harb. Perspect. Biol. 2011, 3, doi:10.1101/cshperspect.a004978.
[3]
Ninomiya, Y.; Kagawa, M.; Iyama, K.; Naito, I.; Kishiro, Y.; Seyer, J.M.; Sugimoto, M.; Oohashi, T.; Sado, Y. Differential expression of two basement membrane collagen genes, COL4A6 and COL4A5, demonstrated by immunofluorescence staining using peptide-specific monoclonal antibodies. J. Cell. Biol. 1995, 130, 1219–1229, doi:10.1083/jcb.130.5.1219.
Schlotzer-Schrehardt, U.; Dietrich, T.; Saito, K.; Sorokin, L.; Sasaki, T.; Paulsson, M.; Kruse, F.E. Characterization of extracellular matrix components in the limbal epithelial stem cell compartment. Exp. Eye. Res. 2007, 85, 845–860, doi:10.1016/j.exer.2007.08.020.
[6]
Tuori, A.; Uusitalo, H.; Burgeson, R.E.; Terttunen, J.; Virtanen, I. The immunohistochemical composition of the human corneal basement membrane. Cornea 1996, 15, 286–294, doi:10.1097/00003226-199605000-00010.
[7]
Ljubimov, A.V.; Burgeson, R.E.; Butkowski, R.J.; Michael, A.F.; Sun, T.T.; Kenney, M.C. Human corneal basement membrane heterogeneity: Topographical differences in the expression of type IV collagen and laminin isoforms. Lab. Invest. 1995, 72, 461–473.
[8]
Ben-Zvi, A.; Rodrigues, M.M.; Krachmer, J.H.; Fujikawa, L.S. Immunohistochemical characterization of extracellular matrix in the developing human cornea. Curr. Eye. Res. 1986, 5, 105–117, doi:10.3109/02713688609015099.
[9]
White, J.; Werkmeister, J.A.; Ramshaw, J.A.; Birk, D.E. Organization of fibrillar collagen in the human and bovine cornea: collagen types V and III. Connect. Tissue Res. 1997, 36, 165–174, doi:10.3109/03008209709160218.
[10]
Sillat, T.; Saat, R.; Pollanen, R.; Hukkanen, M.; Takagi, M.; Konttinen, Y.T. Basement membrane collagen type IV expression by human mesenchymal stem cells during adipogenic differentiation. J. Cell. Mol. Med. 2012, 16, 1485–1495, doi:10.1111/j.1582-4934.2011.01442.x.
[11]
Li, D.Q.; Chen, Z.; Song, X.J.; de Paiva, C.S.; Kim, H.S.; Pflugfelder, S.C. Partial enrichment of a population of human limbal epithelial cells with putative stem cell properties based on collagen type IV adhesiveness. Exp. Eye. Res. 2005, 80, 581–590, doi:10.1016/j.exer.2004.11.011.
[12]
Homma, R.; Yoshikawa, H.; Takeno, M.; Kurokawa, M.S.; Masuda, C.; Takada, E.; Tsubota, K.; Ueno, S.; Suzuki, N. Induction of epithelial progenitors in vitro from mouse embryonic stem cells and application for reconstruction of damaged cornea in mice. Invest. Ophthalmol. Vis. Sci. 2004, 45, 4320–4326, doi:10.1167/iovs.04-0044.
[13]
Ahmad, S.; Stewart, R.; Yung, S.; Kolli, S.; Armstrong, L.; Stojkovic, M.; Figueiredo, F.; Lako, M. Differentiation of human embryonic stem cells into corneal epithelial-like cells by in vitro replication of the corneal epithelial stem cell niche. Stem Cells 2007, 25, 1145–1155, doi:10.1634/stemcells.2006-0516.
[14]
Blazejewska, E.A.; Schlotzer-Schrehardt, U.; Zenkel, M.; Bachmann, B.; Chankiewitz, E.; Jacobi, C.; Kruse, F.E. Corneal limbal microenvironment can induce transdifferentiation of hair follicle stem cells into corneal epithelial-like cells. Stem Cells 2009, 27, 642–652, doi:10.1634/stemcells.2008-0721.
[15]
Builles, N.; Janin-Manificat, H.; Malbouyres, M.; Justin, V.; Rovere, M.R.; Pellegrini, G.; Torbet, J.; Hulmes, D.J.; Burillon, C.; Damour, O.; Ruggiero, F. Use of magnetically oriented orthogonal collagen scaffolds for hemi-corneal reconstruction and regeneration. Biomaterials 2010, 31, 8313–8322.
[16]
Torbet, J.; Malbouyres, M.; Builles, N.; Justin, V.; Roulet, M.; Damour, O.; Oldberg, A.; Ruggiero, F.; Hulmes, D.J. Orthogonal scaffold of magnetically aligned collagen lamellae for corneal stroma reconstruction. Biomaterials 2007, 28, 4268–4276.
[17]
McIntosh Ambrose, W.; Salahuddin, A.; So, S.; Ng, S.; Ponce Marquez, S.; Takezawa, T.; Schein, O.; Elisseeff, J. Collagen vitrigel membranes for the in vitro reconstruction of separate corneal epithelial, stromal, and endothelial cell layers. J. Biomed. Mater. Res. B Appl. Biomater. 2009, 90, 818–831.
[18]
Jones, R.R.; Hamley, I.W.; Connon, C.J. Ex vivo expansion of limbal stem cells is affected by substrate properties. Stem Cell Res. 2012, 8, 403–409, doi:10.1016/j.scr.2012.01.001.
[19]
Labat-Robert, J. Cell-Matrix interactions, the role of fibronectin and integrins: A survey. Pathol. Biol. 2012, 60, 15–19, doi:10.1016/j.patbio.2011.10.003.
[20]
Muro, A.F.; Chauhan, A.K.; Gajovic, S.; Iaconcig, A.; Porro, F.; Stanta, G.; Baralle, F.E. Regulated splicing of the fibronectin EDA exon is essential for proper skin wound healing and normal lifespan. J. Cell. Biol. 2003, 162, 149–160, doi:10.1083/jcb.200212079.
[21]
Gu, Y.C.; Kortesmaa, J.; Tryggvason, K.; Persson, J.; Ekblom, P.; Jacobsen, S.E.; Ekblom, M. Laminin isoform-specific promotion of adhesion and migration of human bone marrow progenitor cells. Blood 2003, 101, 877–885, doi:10.1182/blood-2002-03-0796.
[22]
Thibault, M.M.; Hoemann, C.D.; Buschmann, M.D. Fibronectin, vitronectin, and collagen I induce chemotaxis and haptotaxis of human and rabbit mesenchymal stem cells in a standardized transmembrane assay. Stem Cells Dev. 2007, 16, 489–502, doi:10.1089/scd.2006.0100.
[23]
Trinh, L.A.; Stainier, D.Y. Fibronectin regulates epithelial organization during myocardial migration in zebrafish. Dev. Cell. 2004, 6, 371–382, doi:10.1016/S1534-5807(04)00063-2.
[24]
Durbeej, M. Laminins. Cell Tissue Res 2010, 339, 259–268, doi:10.1007/s00441-009-0838-2.
[25]
Colognato, H.; Yurchenco, P.D. Form and function: The laminin family of heterotrimers. Dev. Dyn. 2000, 218, 213–234, doi:10.1002/(SICI)1097-0177(200006)218:2<213::AID-DVDY1>3.0.CO;2-R.
[26]
Kabosova, A.; Azar, D.T.; Bannikov, G.A.; Campbell, K.P.; Durbeej, M.; Ghohestani, R.F.; Jones, J.C.; Kenney, M.C.; Koch, M.; Ninomiya, Y.; Patton, B.L.; Paulsson, M.; Sado, Y.; Sage, E.H.; Sasaki, T.; Sorokin, L.M.; Steiner-Champliaud, M.F.; Sun, T.T.; Sundarraj, N.; Timpl, R.; Virtanen, I.; Ljubimov, A.V. Compositional differences between infant and adult human corneal. Invest. Ophthalmol. Vis Sci. 2007, 48, 4989–4999.
[27]
Dietlein, T.S.; Jacobi, P.C.; Paulsson, M.; Smyth, N.; Krieglstein, G.K. Variability of laminin isoforms in the limbus region of the eye. Klin. Monbl. Augenheilkd. 1997, 211, 188–191, doi:10.1055/s-2008-1035120.
[28]
Siler, U.; Seiffert, M.; Puch, S.; Richards, A.; Torok-Storb, B.; Muller, C.A.; Sorokin, L.; Klein, G. Characterization and functional analysis of laminin isoforms in human bone marrow. Blood 2000, 96, 4194–4203.
[29]
Pouliot, N.; Saunders, N.A.; Kaur, P. Laminin 10/11: An alternative adhesive ligand for epidermal keratinocytes with a functional role in promoting proliferation and migration. Exp. Dermatol. 2002, 11, 387–397, doi:10.1034/j.1600-0625.2002.110501.x.
[30]
Nakaji-Hirabayashi, T.; Kato, K.; Iwata, H. Improvement of neural stem cell survival in collagen hydrogels by incorporating laminin-derived cell adhesive polypeptides. Bioconjug. Chem. 2012, 23, 212–221, doi:10.1021/bc200481v.
[31]
Malan, D.; Reppel, M.; Dobrowolski, R.; Roell, W.; Smyth, N.; Hescheler, J.; Paulsson, M.; Bloch, W.; Fleischmann, B.K. Lack of laminin gamma1 in embryonic stem cell-derived cardiomyocytes causes inhomogeneous electrical spreading despite intact differentiation and function. Stem Cells 2009, 27, 88–99, doi:10.1634/stemcells.2008-0335.
Meng, X.; Klement, J.F.; Leperi, D.A.; Birk, D.E.; Sasaki, T.; Timpl, R.; Uitto, J.; Pulkkinen, L. Targeted inactivation of murine laminin gamma2-chain gene recapitulates human junctional epidermolysis bullosa. J. Invest. Dermatol. 2003, 121, 720–731, doi:10.1046/j.1523-1747.2003.12515.x.
[34]
Kuster, J.E.; Guarnieri, M.H.; Ault, J.G.; Flaherty, L.; Swiatek, P.J. IAP insertion in the murine LamB3 gene results in junctional epidermolysis bullosa. Mamm. Genome 1997, 8, 673–681, doi:10.1007/s003359900535.
[35]
Fukumoto, S.; Miner, J.H.; Ida, H.; Fukumoto, E.; Yuasa, K.; Miyazaki, H.; Hoffman, M.P.; Yamada, Y. Laminin alpha5 is required for dental epithelium growth and polarity and the development of tooth bud and shape. J. Biol. Chem. 2006, 281, 5008–5016.
[36]
Ryan, M.C.; Lee, K.; Miyashita, Y.; Carter, W.G. Targeted disruption of the LAMA3 gene in mice reveals abnormalities in survival and late stage differentiation of epithelial cells. J. Cell. Biol. 1999, 145, 1309–1323, doi:10.1083/jcb.145.6.1309.
[37]
Li, J.; Tzu, J.; Chen, Y.; Zhang, Y.P.; Nguyen, N.T.; Gao, J.; Bradley, M.; Keene, D.R.; Oro, A.E.; Miner, J.H.; Marinkovich, M.P. Laminin-10 is crucial for hair morphogenesis. EMBO J. 2003, 22, 2400–2410, doi:10.1093/emboj/cdg239.
[38]
Preissner, K.T.; Reuning, U. Vitronectin in vascular context: Facets of a multitalented matricellular protein. Semin. Thromb. Hemost. 2011, 37, 408–424, doi:10.1055/s-0031-1276590.
[39]
Echevarria, T.J.; Chow, S.; Watson, S.; Wakefield, D.; Di Girolamo, N. Vitronectin: A matrix support factor for human limbal epithelial progenitor cells. Invest. Ophthalmol. Vis. Sci. 2011, 52, 8138–8147, doi:10.1167/iovs.11-8140.
[40]
Kundu, A.K.; Putnam, A.J. Vitronectin and collagen I differentially regulate osteogenesis in mesenchymal stem cells. Biochem. Biophys. Res. Commun. 2006, 347, 347–357, doi:10.1016/j.bbrc.2006.06.110.
[41]
Salasznyk, R.M.; Williams, W.A.; Boskey, A.; Batorsky, A.; Plopper, G.E. Adhesion to vitronectin and collagen I promotes osteogenic differentiation of human mesenchymal stem cells. J. Biomed. Biotechnol. 2004, 24–34.
[42]
Hurt, E.M.; Chan, K.; Serrat, M.A.; Thomas, S.B.; Veenstra, T.D.; Farrar, W.L. Identification of vitronectin as an extrinsic inducer of cancer stem cell differentiation and tumor formation. Stem Cells 2010, 28, 390–398.
[43]
Jones, F.S.; Jones, P.L. The tenascin family of ECM glycoproteins: Structure, function, and regulation during embryonic development and tissue remodeling. Dev. Dyn. 2000, 218, 235–259, doi:10.1002/(SICI)1097-0177(200006)218:2<235::AID-DVDY2>3.0.CO;2-G.
[44]
Oberhauser, A.F.; Marszalek, P.E.; Erickson, H.P.; Fernandez, J.M. The molecular elasticity of the extracellular matrix protein tenascin. Nature 1998, 393, 181–185, doi:10.1038/30270.
[45]
Midwood, K.S.; Hussenet, T.; Langlois, B.; Orend, G. Advances in tenascin-C biology. Cell. Mol. Life Sci. CMLS 2011, 68, 3175–3199, doi:10.1007/s00018-011-0783-6.
[46]
Chiquet-Ehrismann, R.; Chiquet, M. Tenascins: Regulation and putative functions during pathological stress. J. Pathol. 2003, 200, 488–499, doi:10.1002/path.1415.
[47]
Orend, G. Potential oncogenic action of tenascin-C in tumorigenesis. Int. J. Biochem. Cell Biol. 2005, 37, 1066–1083, doi:10.1016/j.biocel.2004.12.002.
[48]
Nakamura-Ishizu, A.; Okuno, Y.; Omatsu, Y.; Okabe, K.; Morimoto, J.; Uede, T.; Nagasawa, T.; Suda, T.; Kubota, Y. Extracellular matrix protein tenascin-C is required in the bone marrow microenvironment primed for hematopoietic regeneration. Blood 2012, 119, 5429–5437.
[49]
Maseruka, H.; Ridgway, A.; Tullo, A.; Bonshek, R. Developmental changes in patterns of expression of tenascin-C variants in the human cornea. Invest. Ophthalmol. Vis. Sci. 2000, 41, 4101–4107.
[50]
Ding, Z.; Dong, J.; Liu, J.; Deng, S.X. Preferential gene expression in the limbus of the vervet monkey. Mol. Vis. 2008, 14, 2031–2041.
[51]
Ljubimov, A.V.; Saghizadeh, M.; Spirin, K.S.; Mecham, R.P.; Sakai, L.Y.; Kenney, M.C. Increased expression of fibrillin-1 in human corneas with bullous keratopathy. Cornea 1998, 17, 309–314, doi:10.1097/00003226-199805000-00012.
[52]
Maseruka, H.; Bonshek, R.E.; Tullo, A.B. Tenascin-C expression in normal, inflamed, and scarred human corneas. Br. J. Ophthalmol. 1997, 81, 677–682, doi:10.1136/bjo.81.8.677.
[53]
Tervo, K.; van Setten, G.B.; Beuerman, R.W.; Virtanen, I.; Tarkkanen, A.; Tervo, T. Expression of tenascin and cellular fibronectin in the rabbit cornea after anterior keratectomy. Immunohistochemical study of wound healing dynamics. Invest. Ophthalmol. Vis. Sci. 1991, 32, 2912–2918.
Sta Iglesia, D.D.; Gala, P.H.; Qiu, T.; Stepp, M.A. Integrin expression during epithelial migration and restratification in the tenascin-C-deficient mouse cornea. J. Histochem. Cytochem. 2000, 48, 363–376.
[56]
Sage, H.; Vernon, R.B.; Funk, S.E.; Everitt, E.A.; Angello, J. SPARC, a secreted protein associated with cellular proliferation, inhibits cell spreading in vitro and exhibits Ca+2—Dependent binding to the extracellular matrix. J. Cell. Biol. 1989, 109, 341–356.
[57]
Termine, J.D.; Kleinman, H.K.; Whitson, S.W.; Conn, K.M.; McGarvey, M.L.; Martin, G.R. Osteonectin, a bone-specific protein linking mineral to collagen. Cell 1981, 26, 99–105, doi:10.1016/0092-8674(81)90037-4.
Mishima, H.; Hibino, T.; Hara, H.; Murakami, J.; Otori, T. SPARC from corneal epithelial cells modulates collagen contraction by keratocytes. Invest. Ophthalmol. Vis. Sci. 1998, 39, 2547–2553.
[60]
Latvala, T.; Puolakkainen, P.; Vesaluoma, M.; Tervo, T. Distribution of SPARC protein (osteonectin) in normal and wounded feline cornea. Exp. Eye Res. 1996, 63, 579–584, doi:10.1006/exer.1996.0148.
[61]
Abe, K.; Hibino, T.; Mishima, H.; Shimomura, Y. The cytokine regulation of SPARC production by rabbit corneal epithelial cells and fibroblasts in vitro. Cornea 2004, 23, 172–179, doi:10.1097/00003226-200403000-00011.
[62]
Shimmura, S.; Miyashita, H.; Higa, K.; Yoshida, S.; Shimazaki, J.; Tsubota, K. Proteomic analysis of soluble factors secreted by limbal fibroblasts. Mol. Vis. 2006, 12, 478–484.
[63]
Katz, A.; Fish, A. J.; Pe’er, J.; Frucht-Pery, J.; Ron, N.; Vlodavsky, I. Entactin/nidogen: Synthesis by bovine corneal endothelial cells and distribution in the human cornea. Invest. Ophthalmol. Vis. Sci. 1994, 35, 495–502.
[64]
Mishima, H.; Hibino, T.; Hara, H.; Otori, T. Entactin modulates the attachment of rabbit corneal epithelial cells. Curr. Eye. Res. 1996, 15, 733–738.
Bezakova, G.; Ruegg, M.A. New insights into the roles of agrin. Nat. Rev. Mol. Cell. Biol. 2003, 4, 295–308.
[68]
Kim, N.; Stiegler, A.L.; Cameron, T.O.; Hallock, P.T.; Gomez, A.M.; Huang, J.H.; Hubbard, S.R.; Dustin, M.L.; Burden, S.J. Lrp4 is a receptor for agrin and forms a complex with MuSK. Cell 2008, 135, 334–342.
[69]
Mazzon, C.; Anselmo, A.; Cibella, J.; Soldani, C.; Destro, A.; Kim, N.; Roncalli, M.; Burden, S.J.; Dustin, M.L.; Sarukhan, A.; Viola, A. The critical role of agrin in the hematopoietic stem cell niche. Blood 2011, 118, 2733–2742.
[70]
Fuerst, P.G.; Rauch, S.M.; Burgess, R.W. Defects in eye development in transgenic mice overexpressing the heparan sulfate proteoglycan agrin. Dev. Biol. 2007, 303, 165–180.
[71]
Knox, S.M.; Whitelock, J.M. Perlecan: How does one molecule do so many things? Cell. Mol. Life Sci. 2006, 63, 2435–2445.
Wight, T.N. Versican: A versatile extracellular matrix proteoglycan in cell biology. Curr. Opin. Cell. Biol. 2002, 14, 617–623.
[74]
Chan, C.K.; Rolle, M.W.; Potter-Perigo, S.; Braun, K.R.; Van Biber, B.P.; Laflamme, M.A.; Murry, C.E.; Wight, T.N. Differentiation of cardiomyocytes from human embryonic stem cells is accompanied by changes in the extracellular matrix production of versican and hyaluronan. J. Cell. Biochem. 2010, 111, 585–596.
[75]
Choocheep, K.; Hatano, S.; Takagi, H.; Watanabe, H.; Kimata, K.; Kongtawelert, P. Versican facilitates chondrocyte differentiation and regulates joint morphogenesis. J. Biol. Chem. 2010, 285, 21114–21125.
[76]
Koga, T.; Inatani, M.; Hirata, A.; Inomata, Y.; Zako, M.; Kimata, K.; Oohira, A.; Gotoh, T.; Mori, M.; Tanihara, H. Expression of a chondroitin sulfate proteoglycan, versican (PG-M), during development of rat corne. Curr. Eye Res. 2005, 30, 455–463.