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Pluripotent Stem Cells and Other Innovative Strategies for the Treatment of Ocular Surface Diseases

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Abstract

The cornea provides two thirds of the refractive power of the eye and protection against insults such as infection and injury. The outermost tissue of the cornea is renewed by stem cells located in the limbus. Depletion or destruction of these stem cells may lead to blinding limbal stem cell deficiency (LSCD) that concerns millions of patients around the world. Innovative strategies based on adult stem cell therapies have been developed in the recent years but they are still facing numerous unresolved issues, and the long term results can be deceiving. Today there is a clear need to improve these therapies, and/or to develop new approaches for the treatment of LSCD. Here, we review the current cell-based therapies used for the treatment of ocular diseases, and discuss the potential of pluripotent stem cells (embryonic and induced pluripotent stem cells) in corneal repair. As the secretion of paracrine factors is known to have a crucial role in maintaining stem cell homeostasis and in wound repair, we also consider the therapeutic potential of a promising novel pathway, the exosomes. Exosomes are nano-sized vesicles that have the ability to transfer RNAs and proteins to recipient cells, and several studies demonstrated their role in cell protection and wound healing. Exosomes could circumvent the hurdles of stem-cell based approaches, and they could become a strong candidate as an alternative therapy for ocular surface diseases.

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References

  1. Echevarria, T. J., & Di Girolamo, N. (2011). Tissue-regenerating, vision-restoring corneal epithelial stem cells. Stem Cell Reviews and Reports, 7(2), 256–268.

    Article  PubMed  Google Scholar 

  2. Ahmad, S. (2012). Concise review- LSCD, dysfunction and distress. Stem Cells Translational Medicine, 1(2), 110–115.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Pellegrini, G., Rama, P., Di Rocco, A., Panaras, A., & De Lucas, M. (2014). Concise review: hurdles in a successful example of limbal stem cell based regenerative medicine. Stem Cells, 32(1), 26–34.

    Article  PubMed  Google Scholar 

  4. He, H., & Yiu, S. C. (2014). Stem cell-based therapy for treating limbal stem cells deficiency: a review of different strategies. Saudi Journal Ophthalmology, 28(3), 188–194.

    Article  Google Scholar 

  5. Vemuganti, G. K., Fatima, A., Madhira, S. L., Basti, S., & Sangwan, V. S. (2009). Limbal stem cells: application in ocular biomedicine. International Review of Cell and Molecular Biology, 275, 133–181.

    Article  PubMed  Google Scholar 

  6. Espana, E. M., Di Pascuale, M., Grueterich, M., Solomon, A., & Tseng, S. C. G. (2004). Keratolimbal allograft in corneal reconstruction. Eye (London), 18(4), 406–417.

    Article  CAS  Google Scholar 

  7. Sejpal, K., Bakhtiari, P., & Deng, S. X. (2013). Presentation, diagnosis and management of limbal stem cell deficiency. Middle East African Journal of Ophthalmology, 20(1), 5–10.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Anderson, D. F. (2001). Amniotic membrane transplantation for partial limbal stem cell deficiency. British Journal of Ophthalmology, 85(5), 567–575.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Pellegrini, G., Traverso, C. E., Franzi, A. T., Zingirian, M., Cancceda, R., & De Lucas, M. (1997). Long-term restoration of damaged corneal surfaces with autologous cultivated corneal epithelium. Lancet, 349(9057), 990–993.

    Article  CAS  PubMed  Google Scholar 

  10. Sangwan, V. S., Matalia, H. P., Vermuganti, G. K., Fatima, A., Ifthekar, G., Singh, S., et al. (2006). Clinical outcome of autologous cultivated limbal epithelium transplantation. Indian Journal of Ophthalmology, 54(1), 29–34.

    Article  PubMed  Google Scholar 

  11. Rama, P., Matuska, S., Paganoni, G., Spinelli, A., De Lucas, M., & Pelligrini, G. (2010). Limbal stem-cell therapy and long-term corneal regeneration. New England Journal of Medicine, 363(2), 147–155.

    Article  CAS  PubMed  Google Scholar 

  12. Shortt, A. J., Secker, G. A., Notara, M. D., Limb, G. A., Khaw, P. T., Tuft, S. J., et al. (2007). Transplantation of ex vivo cultured limbal epithelial stem cells: a review of techniques and clinical results. Survey of Ophthalmology, 52(5), 483–502.

    Article  PubMed  Google Scholar 

  13. Di Girolamo, N., Bosch, M., Zamora, K., Coroneo, M. T., Wakefield, D., & Watson, S. L. (2009). A contact lens-based technique for expansion and transplantation of autologous epithelial progenitors for ocular surface reconstruction. Transplantation, 87(10), 1571–1578.

    Article  PubMed  Google Scholar 

  14. Baylis, O., Figueiredo, F., Henein, C., Lako, M., & Ahmad, S. (2011). 13 Years of cultured limbal epithelial cell therapy: a review of the outcomes. Journal of Cellular Biochemistry, 112(4), 993–1002.

    Article  CAS  PubMed  Google Scholar 

  15. Hayashida, Y., Nishida, K., Yamato, M., Watanabe, K., Maeda, N., Watanabe, H., et al. (2005). Ocular surface reconstruction using autologous rabbit oral mucosal epithelial sheets fabricated ex vivo on a temperature-responsive culture surface. Investigative Ophthalmology and Visual Science, 46(5), 1632–1639.

    Article  PubMed  Google Scholar 

  16. Inatomi, T., Nakamura, T., Koizumi, N., Sotozono, C., Yokoi, N., & Kinoskita, S. (2006). Midterm results on ocular surface reconstruction using cultivated autologous oral mucosal epithelial transplantation. American Journal of Ophthalmology, 141(2), 267–275.

    Article  PubMed  Google Scholar 

  17. Kolli, S., Ahmad, S., Mudhar, H. S., Meeny, A., Lako, M., & Fequeiredo, F. C. (2014). Successful application of ex vivo expanded human autologous oral mucosal epithelium for the treatment of total bilateral limbal stem cell deficiency. Stem Cells, 32(8), 2135–2146.

    Article  CAS  PubMed  Google Scholar 

  18. Priya, C. G., Arpitha, P., Vaishali, S., Prajna, N. V., Usha, K., Sheetal, K., et al. (2011). Adult human buccal epithelial stem cells: identification, ex-vivo expansion, and transplantation for corneal surface reconstruction. Eye (London), 25(12), 1641–1649.

    Article  CAS  Google Scholar 

  19. Burillon, C., Huot, L., Justin, V., Nataf, S., Chapuis, F., Decullier, E., et al. (2012). Cultured autologous oral mucosal epithelial cell sheet (CAOMECS) transplantation for the treatment of corneal limbal epithelial stem cell deficiency. Investigative Ophthalmology and Visual Science, 53(3), 1325–1331.

    Article  PubMed  Google Scholar 

  20. Sotozono, C., Inatomi, T., Nakamura, T., Koizumi, N., Yokoi, N., Ueta, M., et al. (2014). Cultivated oral mucosal epithelial transplantation for persistent epithelial defect in severe ocular surface diseases with acute inflammatory activity. Acta Ophthalmologica, 92(6), e447–e453.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Utheim, T. P. (2015). Concise review: transplantation of cultured oral mucosal epithelial cells for treating limbal stem cell deficiency-current status and future perspectives. Stem Cells, 33, 1685–1695.

    Article  CAS  PubMed  Google Scholar 

  22. Chun, Y. S., Park, I. K., & Kim, J. C. (2011). Technique for autologous nasal mucosa transplantation in severe ocular surface disease. European Journal of Ophtalmology, 21(5), 545–551.

    Article  Google Scholar 

  23. Konno, M., Hamabe, A., Hasegawa, S., Ogawa, H., Fukusumi, T., Nishikawa, et al. (2013). Adipose-derived mesenchymal stem cells and regenerative medicine. Development Growth and Differentiation, 55(3), 309–318.

    Article  CAS  Google Scholar 

  24. Ma, Y., Xu, Y., Xiao, Z., Yang, W., Zhang, C., Song, E., et al. (2006). Reconstruction of chemically burned rat corneal surface by bone marrow-derived human mesenchymal stem cells. Stem Cells, 24(2), 315–321.

    Article  PubMed  Google Scholar 

  25. Gu, S., Xing, C., Han, J., Tso, M. O. M., & Hong, J. (2009). Differentiation of rabbit bone marrow mesenchymal stem cells into corneal epithelial cells in vivo and ex vivo. Molecular Vision, 15, 99–107.

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Jiang, T.-S., Cai, L., Ji, W. Y., Hui, Y. N., Wang, Y. S., Hu, D., et al. (2010). Reconstruction of the corneal epithelium with induced marrow mesenchymal stem cells in rats. Molecular Vision, 16, 1304–1316.

    PubMed  PubMed Central  Google Scholar 

  27. Nieto-Miguel, T., Galindo, S., Reinoso, R., Corell, A., Martino, M., Perez-Simon, J. A., et al. (2013). et al. In vitro simulation of corneal epithelium microenvironment induces a corneal epithelial-like cell phenotype from human adipose tissue mesenchymal stem cells. Current Eye Research, 38(9), 933–944.

    Article  CAS  PubMed  Google Scholar 

  28. Advanced Therapy for Ocular Surface Reconstruction. Allogenic Limbus Epithelial Stem-cell Transplant vs Bone Marrow Mesenchymal Stem-cell Transplant in Limbus Insufficiency Syndrome. Double-masked Randomized Trial. ClinicalTrials.gov identifier: NCT015620. Available at clinicaltrials.gov

  29. The Subconjunctival Injection of Human Bone Marrow Mesenchymal Stem Cells for Ocular Corneal Burn: Prospective, Double-blind, Randomized, Controlled Trial. ClinicalTrials.gov identifier: NCT02325843. Available at clinicaltrials.gov

  30. Monteiro, B. G., Serafim, R. C., Melo, G. B., Silva, M. C., Lizier, N. F., Maranduba, C. M., et al. (2009). Human immature dental pulp stem cells share key characteristic features with limbal stem cells. Cell Proliferation, 42(5), 587–594.

    Article  CAS  PubMed  Google Scholar 

  31. Reza, H. M., Ng, B.-Y., Gimeno, F. L., Phan, T. T., & Ang, L. P.-K. (2011). Umbilical cord lining stem cells as a novel and promising source for ocular surface regeneration. Stem Cell Reviews, 7(4), 935–947.

    Article  PubMed  Google Scholar 

  32. Meyer-Blazejewska, E. A., Call, M. K., Yamanaka, O., Liu, H., Schlotzer-Schrehardt, U., et al. (2011). From hair to cornea: toward the therapeutic use of hair follicle-derived stem cells in the treatment of limbal stem cell deficiency. Stem Cells, 29(1), 57–66.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Wernig, M., Meissner, A., Foreman, R., Brambrink, T., Ku, M., & Hochedlinger, K. (2007). In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state. Nature, 448(7151), 318–324.

    Article  CAS  PubMed  Google Scholar 

  34. Okita, K., Ichisaka, T., & Yamanaka, S. (2007). Generation of germline-competent induced pluripotent stem cells. Nature, 448(7151), 313–317.

    Article  CAS  PubMed  Google Scholar 

  35. Thomson, J. A., Itskovitz-Eldor, J., Shapiro, S. S., Waknitz, M. A., Swiergiel, J. J., Marshall, V. S., et al. (1998). Embryonic stem cell lines derived from human blastocysts. Science, 282(5391), 1145–1147.

    Article  CAS  PubMed  Google Scholar 

  36. De Lázaro, I., Yilmazer, A., & Kostarelos, K. (2014). Induced pluripotent stem (iPS) cells: a new source for cell-based therapeutics? Journal of Controlled Release, 185, 37–44.

    Article  PubMed  Google Scholar 

  37. Cloutier, F., Siegenthaler, M. M., Nistor, G., & Keirstead, H. S. (2006). Transplantation of human embryonic stem cell-derived oligodendrocyte progenitors into rat spinal cord injuries does not cause harm. Regenerative Medicine, 1(14), 469–479.

    Article  CAS  PubMed  Google Scholar 

  38. Pêgo, A. P., Kubinova, S., Cizkova, D., Vanicky, I., Mar, F. M., Sousa, M. M., et al. (2012). Regenerative medicine for the treatment of spinal cord injury: more than just promises? Journal of Cellular and Molecular Medicine, 16(11), 2564–2582.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Hanna, J., Wernig, M., Markoulaki, S., Sun, C. W., Meissner, A., Cassady, J. P., et al. (2007). Treatment of sickle cell anemia mouse model with iPS cells generated from autologous skin. Science, 318(5858), 1920–1923.

    Article  CAS  PubMed  Google Scholar 

  40. Li, Z., Wu, J. C., Sheikh, A. Y., Kraft, D., Cao, F., Xie, X., et al. (2007). Differentiation, survival, and function of embryonic stem cell derived endothelial cells for ischemic heart disease. Circulation, 116(11 Suppl), I46–I54.

    PubMed  PubMed Central  Google Scholar 

  41. Laflamme, M. A., Chen, K. Y., Naumova, A. V., Muskheli, V., Fugate, J. A., Dupras, S. K., et al. (2007). Cardiomyocytes derived from human embryonic stem cells in pro-survival factors enhance function of infarcted rat hearts. Nature Biotechnology, 25(9), 1015–1024.

    Article  CAS  PubMed  Google Scholar 

  42. Chong, J. J., Yang, X., Don, C. W., Minami, E., Liu, Y. W., Weyers, J. J., et al. (2014). Human embryonic-stem-cell-derived cardiomyocytes regenerate non-human primate hearts. Nature, 510(7504), 273–277.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Kawamura, M., Miyagawa, S., Fukushima, S., Saito, A., Miki, K., Ito, E., et al. (2013). Enhanced survival of transplanted human induced pluripotent stem cell-derived cardiomyocytes by the combination of cell sheets with the pedicled omental flap technique in a porcine heart. Circulation, 128(11 Suppl1), S87–S94.

    Article  PubMed  Google Scholar 

  44. Christoforou, N., Oskouei, B. N., Esteso, P., Hill, C. M., Zimmet, J. M., Bian, W., et al. (2010). Implantation of mouse embryonic stem cell-derived cardiac progenitor cells preserves function of infarcted murine hearts. PloS One, 5(7), e11536.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Xiong, Q., Ye, L., Zhang, P., Lepley, M., Tian, J., Li, J., et al. (2013). Functional consequences of human induced pluripotent stem cell therapy: myocardial ATP turnover rate in the in vivo swine heart with postinfarction remodeling. Circulation, 127(9), 997–1008.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Darabi, R., Arpke, R. W., Irion, S., Dimos, J. T., Grskovic, M., Kyba, M., et al. (2012). Human ES- and iPS-derived myogenic progenitors restore DYSTROPHIN and improve contractility upon transplantation in dystrophic mice. Cell Stem Cell, 10(5), 610–619.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Gonzalez-Cordero, A., West, E. L., Pearson, R. A., Duran, Y., Carvalho, L. S., Chu, C. J., et al. (2013). Photoreceptor precursors derived from three-dimensional embryonic stem cell cultures integrate and mature within adult degenerate retina. Nature Biotechnology, 31(8), 741–747.

    Article  CAS  PubMed  Google Scholar 

  48. Soria, B., Roche, E., Berna, G., Leon-Quinto, T., Reig, J. A., & Martin, F. (2000). Insulin-secreting cells derived from embryonic stem cells normalize glycemia in streptozotocin-induced diabetic mice. Diabetes, 49(2), 157–162.

    Article  CAS  PubMed  Google Scholar 

  49. Antonica, F., Kasprzyk, D. F., Opitz, R., Iacovino, M., Liao, X. H., & Dumitrescu, A. M. (2012). Generation of functional thyroid from embryonic stem cells. Nature, 491(7422), 66–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Schwartz, S. D., Regillo, C. D., Lam, B. L., Eliott, D., Rosenfeld, P. J., Gregori, N. Z., et al. (2014). Human embryonic stem cell-derived retinal pigment epithelium in patients with age-related macular degeneration and Stargardt’s macular dystrophy: follow-up of two open-label phase 1/2 studies. Lancet, 385(9967), 509–516.

    Article  PubMed  Google Scholar 

  51. Menasché, P., Vanneaux, V., Hagège, A., Bel, A., Cholley, B., Cacciapuoti, I., et al. (2015). Human embryonic stem cell-derived cardiac progenitors for severe heart failure treatment: first clinical case report. European Heart Journal, 36(30), 2011–2017.

    Article  PubMed  Google Scholar 

  52. Alonso-Alonso, M. L., & Srivastava, G. K. (2015). Current focus of stem cell application in retinal repair. World Journal of Stem Cells, 7(30), 641–648.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Kamao, H., Mandai, M., Okamoto, S., Sakai, N., Suga, A., Sugita, S., et al. (2014). Characterization of human induced pluripotent stem cell-derived retinal pigment epithelium cell sheets aiming for clinical application. Stem Cell Reports, 2(2), 205–218.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Nakano-Okuno, M., Borah, B. R., & Nakano, I. (2014). Ethics of iPSC-based clinical research for age-related macular degeneration: patient-centered risk-benefit analysis. Stem Cell Reviews, 10(6), 743–752.

    Article  PubMed  PubMed Central  Google Scholar 

  55. RIKEN and Foundation for Biomedical Research and Innovation (2015) Report available at http://www.riken-ibri.jp/AMD/img/20150319.pdf in Japanese

  56. Aberdam, E., Barak, E., Rouleau, M., de LaForest, S., Berrih-Aknin, S., Suter, D. M., et al. (2008). A pure population of ectodermal cells derived from human embryonic stem cells. Stem Cells, 26(2), 440–444.

    Article  CAS  PubMed  Google Scholar 

  57. Wolosin, J. M., Budak, M. T., & Akinci, M. A. (2004). Ocular surface epithelial and stem cell development. International Journal of Developmental Biology, 48(8–9), 981–991.

    Article  PubMed  Google Scholar 

  58. Homma, R., Yoshikawa, H., Takeno, M., Kurokawa, M. S., Masuda, C., Takada, E., et al. (2004). Induction of epithelial progenitors in vitro from mouse embryonic stem cells and application for reconstruction of damaged cornea in mice. Investigative Ophthalmology and Visual Science, 45(12), 4320–4326.

    Article  PubMed  Google Scholar 

  59. Ahmad, S., Stewart, R., Yung, S., Kolli, S., Armstrong, L., Stojkovic, M., et al. (2007). Differentiation of human embryonic stem cells into corneal epithelial-like cells by in vitro replication of the corneal epithelial stem cell niche. Stem Cells, 25(5), 1145–1155.

    Article  CAS  PubMed  Google Scholar 

  60. Notara, M., Hernandez, D., Mason, C., & Daniels, J. T. (2012). Characterization of the phenotype and functionality of corneal epithelial cells derived from mouse embryonic stem cells. Regenerative Medicine, 7(2), 167–178.

    Article  CAS  PubMed  Google Scholar 

  61. Shalom-Feuerstein, R., Serror, L., De La Forest Divonne, S., Petit, I., Aberdam, E., Camargo, L., et al. (2012). Pluripotent stem cell model reveals essential roles for miR-450b-5p and miR-184 in embryonic corneal lineage specification. Stem Cells, 30(5), 898–909.

    Article  CAS  PubMed  Google Scholar 

  62. Petit, I., Kesner, N. S., Karry, R., Robicsek, O., Aberdam, E., Müller, F. J., et al. (2012). Induced pluripotent stem cells from hair follicles as a cellular model for neurodevelopmental disorders. Stem Cell Research, 8(1), 134–140.

    Article  CAS  PubMed  Google Scholar 

  63. Aberdam, D., Gambaro, K., Rostagno, P., Aberdam, E., De La Forest Divonne, S., & Rouleau, M. (2007). Key role of p63 in BMP-4-induced epidermal commitment of embryonic stem cells. Cell Cycle, 6(3), 291–294.

    Article  CAS  PubMed  Google Scholar 

  64. Hayashi, R., Ishikawa, Y., Kageyama, T., Takashiba, K., Fujioka, T., Tsujikawa, M., et al. (2012). Generation of corneal epithelial cells from induced pluripotent stem cells derived from human dermal fibroblast and corneal limbal epithelium. PloS One, 7(9), 1–10.

    Google Scholar 

  65. Sareen, D., Saghizadeh, M., Ornelas, L., Winkler, M. A., Narwani, K., Sahabian, A., et al. (2014). Differentiation of human limbal-derived induced pluripotent stem cells into limbal-like epithelium. Stem Cells Translational Medicine, 3(9), 1002–1012.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Mikhailova, A., Ilmarinen, T., Uusitalo, H., & Skottman, H. (2014). Small-molecule induction promotes corneal epithelial cell differentiation from human induced pluripotent stem cells. Stem Cell Reports, 2(2), 219–223.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Chan, A. A., Hertsenberg, A. J., Funderburgh, M. L., Mann, M. M., Du, Y., Davoli, K. A., et al. (2013). Differentiation of human embryonic stem cells into cells with corneal keratocyte phenotype. PloS One, 8(2), 1–9.

    Article  Google Scholar 

  68. Taylor, C. J., Peacock, S., Chaudhry, A. N., Bradley, J. A., & Bolton, E. M. (2012). Generating an iPSC bank for HLA-matched tissue transplantation based on known donor and recipient HLA types. Cell Stem Cell, 11(2), 147–152.

    Article  CAS  PubMed  Google Scholar 

  69. Zhu, J., Zhang, K., Sun, Y., Gao, X., Li, Y., Chen, Z., et al. (2013). Reconstruction of functional ocular surface by acellular porcine cornea matrix scaffold and limbal stem cells derived from human embryonic stem cells. Tissue Engineering Part A, 19(21–22), 2412–2425.

    Article  CAS  PubMed  Google Scholar 

  70. Assawachananont, J., Mandai, M., Okamoto, S., Yamada, C., Eiraku, M., Yonemura, S., et al. (2014). Transplantation of embryonic and induced pluripotent stem cell-derived 3D retinal sheets into retinal degenerative mice. Stem Cell Reports, 2(5), 662–674.

    Article  PubMed  PubMed Central  Google Scholar 

  71. Sterneckert, J. L., Reinhardt, P., & Schöler, H. R. (2014). Investigating human disease using stem cell models. Nature Reviews Genetics, 15(9), 625–639.

    Article  CAS  PubMed  Google Scholar 

  72. Lancaster, M. A., & Knoblich, J. A. (2014). Organogenesis in a dish: modeling development and disease using organoid technologies. Science, 345(6194), 1247125.

    Article  PubMed  Google Scholar 

  73. Giri, S., & Bader, A. (2015). A low-cost, high-quality new drug discovery process using patient-derived induced pluripotent stem cells. Drug Discovery Today, 20(1), 37–49.

    Article  PubMed  Google Scholar 

  74. Wang, J., et al. (2015). Generation of clinical-grade human induced pluripotent stem cells in Xeno-free conditions. Stem Cell Research & Therapy, 6, 223.

    Article  Google Scholar 

  75. Watt, F. M., & Hogan, B. L. (2000). Out of Eden: stem cells and their niches. Science, 287(5457), 1427–1430.

    Article  CAS  PubMed  Google Scholar 

  76. Gnecchi, M., Zhang, Z., Ni, A., & Dzau, V. J. (2008). Paracrine mechanisms in adult stem cell signaling and therapy. Circulation Research, 103(11), 1204–1219.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Liu, Z., Wan, P., Duan, H., Zhou, J., Tan, B., Liu, Y., et al. (2013). ES micro-environment enhances stemness and inhibits apoptosis in human limbal stem cells via the maintenance of telomerase activity. PloS One, 8(1), 1–14.

    Google Scholar 

  78. Chien, Y., Liao, Y. W., Liu, D. M., Lin, H. L., Chen, S. J., Chen, H. L., et al. (2012). Corneal repair by human corneal keratocyte-reprogrammed iPSCs and amphiphatic carboxymethyl-hexanoyl chitosan hydrogel. Biomaterials, 33(32), 8003–8016.

    Article  CAS  PubMed  Google Scholar 

  79. Yu, D., Chen, M., Sun, X., & Ge, J. (2013). Differentiation of mouse induced pluripotent stem cells into corneal epithelial-like cells. Cell Biology International, 37(1), 87–94.

    Article  CAS  PubMed  Google Scholar 

  80. Saichanma, S., Bunyaratvej, A., & Sila-Asna, M. (2012). In vitro transdifferentiation of corneal epithelial-like cells from human skin-derived precursor cells. International Journal of Ophtalomogy, 5(2), 158–163.

    CAS  Google Scholar 

  81. Harkin, D. G., et al. (2015). Concise reviews: can mesenchymal stromal cells differentiate into corneal cells? A systematic review of published data. Stem Cells, 33, 785–791.

    Article  CAS  PubMed  Google Scholar 

  82. Wan, P.-X., Wang, B.-W., & Wang, Z.-C. (2015). Importance of the stem cell microenvironment for ophthalmological cell-based therapy. World Journal Stem Cells, 7(2), 448–460.

    Article  Google Scholar 

  83. Dai, Y., et al. (2014). Non-genetic direct reprogramming and biomimetic platforms in a preliminary study for adipose-derived stem cells into corneal endothelia-like cells. PloS One, 9, e109856.

    Article  PubMed  PubMed Central  Google Scholar 

  84. Théry C (2011) Exosomes: secreted vesicles and intercellular communications. F1000 Biology Reports, 3, 15

  85. Colombo, M., Raposo, G., & Théry, C. (2014). Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles. Annual Review of Cell and Developmental Biology, 30, 255–289.

    Article  CAS  PubMed  Google Scholar 

  86. Valadi, H., Ekström, K., Bossios, A., Sjöstrand, M., Lee, J. J., & Lötvall, J. O. (2007). Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nature Cell Biology, 9(6), 654–659.

    Article  CAS  PubMed  Google Scholar 

  87. Nazarenko, I., Rana, S., Baumann, A., McAlear, J., Hellwig, A., Trendelenburg, M., et al. (2010). Cell surface tetraspanin Tspan8 contributes to molecular pathways of exosome-induced endothelial cell activation. Cancer Research, 70(4), 1668–1678.

    Article  CAS  PubMed  Google Scholar 

  88. Lai, R. C., Chen, T. S., & Lim, S. K. (2011). Mesenchymal stem cell exosome: a novel stem cell-based therapy for cardiovascular disease. Regenerative Medicine, 6(4), 481–492.

    Article  PubMed  Google Scholar 

  89. Khan, M., Nickoloff, E., Abramova, T., Johnson, J., Verma, S. K., Krishnamurthy, P., et al. (2015). Embryonic stem cell-derived exosomes promote endogenous repair mechanisms and enhance cardiac function following myocardial infarction. Circulation Research, 117, 52–64.

    Article  CAS  PubMed  Google Scholar 

  90. Zhang, J., Guan, J., Niu, X., Hu, G., Guo, S., Li, Q., et al. (2015). Exosomes released from human induced pluripotent stem cells-derived MSCs facilitate cutaneous wound healing by promoting collagen synthesis and angiogenesis. Journal of Translational Medicine, 13, 49.

    Article  PubMed  PubMed Central  Google Scholar 

  91. Nakamura, Y., Miyaki, S., Ishitobi, H., Matsuyama, S., Nakasa, T., Kamei, N., et al. (2015). Mesenchymal-stem-cell-derived exosomes accelerate skeletal muscle regeneration. FEBS Letter, 589(11), 1257–1265.

    Article  CAS  Google Scholar 

  92. Yu, B., Zhang, X., & Li, X. (2014). Exosomes derived from mesenchymal stem cells. International Journal of Molecular Science, 15(3), 4142–4157.

    Article  CAS  Google Scholar 

  93. Aliotta, J. M., et al. (2007). Alteration of marrow cell gene expression, protein production, and engraftment into lung by lung-derived microvesicles: a novel mechanism for phenotype modulation. Stem Cells, 25, 2245–2256.

    Article  PubMed  PubMed Central  Google Scholar 

  94. Jang, Y.-Y., Collector, M. I., Baylin, S. B., Diehl, A. M., & Sharkis, S. J. (2004). Hematopoietic stem cells convert into liver cells within days without fusion. Nature Cell Biology, 6, 532–539.

    Article  CAS  PubMed  Google Scholar 

  95. Suntres, Z. E. (2013). Therapeutic uses of exosomes. Exosomes Microvescicles, 1, 1–8.

    Google Scholar 

  96. Streilein, J. W. (2003). Ocular immune privilege: the eye takes a dim but practical view of immunity and inflammation. Journal of Leukocyte Biology, 74(2), 179–185.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

The authors acknowledge support from French National Agency for Research (ANR 11 EMMA 023 and ANR-13-PRTS-0001-02) to DA.

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Authors and Affiliations

  1. Cell Therapy Unit, Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Louis, Paris, F-75010, France

    Johanna Erbani, Jerome Larghero & Valérie Vanneaux

  2. INSERM, CIC de Biothérapies (CBT-501) and U1160, Institut Universitaire d’Hématologie, Hôpital Saint-Louis, Paris, 75010, France

    Johanna Erbani, Jerome Larghero & Valérie Vanneaux

  3. University Paris Diderot, Sorbonne Paris Cité, Paris, F-75475, France

    Johanna Erbani, Daniel Aberdam, Jerome Larghero & Valérie Vanneaux

  4. INSERM U976, Hôpital St-Louis, Paris, F-75010, France

    Daniel Aberdam

Authors
  1. Johanna Erbani
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  2. Daniel Aberdam
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  3. Jerome Larghero
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  4. Valérie Vanneaux
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Correspondence to Daniel Aberdam or Valérie Vanneaux.

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Erbani, J., Aberdam, D., Larghero, J. et al. Pluripotent Stem Cells and Other Innovative Strategies for the Treatment of Ocular Surface Diseases. Stem Cell Rev and Rep 12, 171–178 (2016). https://doi.org/10.1007/s12015-016-9643-y

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