Regenerative Therapies in Dry Eye Disease: From Growth Factors to Cell Therapy
Abstract
:1. Introduction
2. Hemoderivatives
2.1. Autologous Serum (AS)
2.2. Allogeneic Serum (ALS)
2.3. Platelet-Rich Plasma (PRP)
2.4. Umbilical Cord Blood Serum (UCS)
3. Stem Cell Therapy
3.1. MSCs (Auto/Allogeneic)
3.2. MSCs Secretome
4. Conclusions
Acknowledgments
Author Contributions
Conflicts of Interest
Abbreviations
DED | Dry eye disease |
AS | Autologous serum |
TGF-β | Transforming growth factor-beta |
PDGF | Platelet-derived growth factor |
EGF | Epidermal growth factor |
NGF | Nerve growth factor |
IGF-1 | Insulin-like growth factor 1 |
VEGF | Vascular endothelial growth factor |
SP | Substance P |
PRP | Platelet-rich plasma |
UCS | Umbilical cord blood serum |
IL | Interleukin |
TNF-α | Tumor necrosis factor-α |
CGRP | Calcitonin gene-related peptide |
ALS | Allogeneic serum |
HGF | Hepatocyte growth factor |
PF-4 | Platelet factor-4 |
PRGF | Plasma rich in growth factors |
PRPGF | Plasma rich in platelet and growth factors |
PC | Platelet concentrate |
LR-PRP | Leukocyte-rich platelet-rich plasma |
LP-PRP | Leukocyte-poor platelet-rich plasma |
MMP-9 | Matrix metallopeptidase 9 |
MSCs | Mesenchymal stem cells or multipotent stromal cells |
MHC-II | Major histocompatibility complex II |
NK | Natural killer cells |
IDO | Indolamine 2,3-dioxygenase |
PGE2 | prostaglandin E2 |
NO | Nitric oxide |
IFN-γ | Interferon-gamma |
LESCs | Limbal epithelial stem cells |
TSP-1 | Thrombospondin-1 |
References
- Craig, J.P.; Nichols, K.K.; Akpek, E.K.; Caffery, B.; Dua, H.S.; Joo, C.K.; Liu, Z.; Nelson, J.D.; Nichols, J.J.; Tsubota, K.; et al. TFOS DEWS II definition and classification report. Ocul. Surf. 2017, 15, 276–283. [Google Scholar] [CrossRef] [PubMed]
- Milner, M.S.; Beckman, K.A.; Luchs, J.I.; Allen, Q.B.; Awdeh, R.M.; Berdahl, J.; Boland, T.S.; Buznego, C.; Gira, J.P.; et al. Dysfunctional tear syndrome: Dry eye disease and associated tear film disorders—New strategies for diagnosis and treatment. Curr. Opin. Ophthalmol. 2017, 27, 3–47. [Google Scholar] [CrossRef] [PubMed]
- Foulks, G.N.; Forstot, S.L.; Donshik, P.C.; Forstot, J.Z.; Goldstein, M.H.; Lemp, M.A.; Nelson, J.D.; Nichols, K.K.; Pflugfelder, S.C.; Tanzer, J.M.; et al. Clinical guidelines for management of dry eye associated with Sjögren disease. Ocul. Surf. 2015, 13, 118–132. [Google Scholar] [CrossRef] [PubMed]
- Stevenson, W.; Chauhan, S.K.; Dana, R. Dry eye disease: An immune-mediated ocular surface disorder. Arch. Ophthalmol. 2012, 130, 90–100. [Google Scholar] [CrossRef] [PubMed]
- Messmer, E.M. The pathophysiology, diagnosis, and treatment of dry eye disease. Dtsch Arztebl Int. 2015, 112, 71–81. [Google Scholar] [PubMed]
- Smith, J.A. The epidemiology of dry eye disease: Report of the Epidemiology Subcommittee of the International Dry Eye WorkShop (2007). Ocul. Surf. 2007, 5, 93–107. [Google Scholar] [CrossRef]
- Stenwall, P.-A.; Bergström, M.; Seiron, P.; Sellberg, F.; Olsson, T.; Knutson, F.; Berglund, D. Improving the anti-inflammatory effect of serum eye drops using allogeneic serum permissive for regulatory T cell induction. Acta Ophthalmol. 2015, 93, 654–657. [Google Scholar] [CrossRef] [PubMed]
- Stapleton, F.; Alves, M.; Bunya, V.Y.; Jalbert, I.; Lekhanont, K.; Malet, F.; Na, K.S.; Schaumberg, D.; Uchino, M.; Vehof, J.; et al. TFOS DEWS II epidemiology report. Ocul. Surf. 2017, 15, 334–365. [Google Scholar] [CrossRef] [PubMed]
- Steven, P.; Braun, T.; Krösser, S.; Gehlsen, U. Influence of aging on severity and anti-inflammatory treatment of experimental dry eye disease. Klin. Monbl. Augenheilkd. 2017, 234, 662–669. [Google Scholar] [PubMed]
- Bron, A.J.; de Paiva, C.S.; Chauhan, S.K.; Bonini, S.; Gabison, E.E.; Jain, S.; Knop, E.; Markoulli, M.; Ogawa, Y.; Perez, V.; et al. TFOS DEWS II pathophysiology report. Ocul. Surf. 2017, 15, 438–510. [Google Scholar] [CrossRef] [PubMed]
- Song, J.K.; Lee, K.; Park, H.Y.; Hyon, J.Y.; Oh, S.-W.; Bae, W.K.; Han, J.-S.; Jung, S.Y.; Um, Y.J.; Lee, G.-H.; et al. Efficacy of carboxymethylcellulose and hyaluronate in dry eye disease: A systematic review and meta-analysis. Korean J. Fam. Med. 2017, 38, 2–7. [Google Scholar] [CrossRef] [PubMed]
- Zhou, X.Q.; Wei, R.L. Topical cyclosporine A in the treatment of dry eye: A systematic review and meta-analysis. Cornea 2014, 33, 760–767. [Google Scholar] [CrossRef] [PubMed]
- Soni, N.G.; Jeng, B.H. Blood-derived topical therapy for ocular surface diseases. Br. J. Ophthalmol. 2016, 100, 22–27. [Google Scholar] [CrossRef] [PubMed]
- Lekhanont, K.; Jongkhajornpong, P.; Anothaisintawee, T.; Chuckpaiwong, V. Undiluted serum eye drops for the treatment of persistent corneal epithelial defects. Sci. Rep. 2016, 6, 38143. [Google Scholar] [CrossRef] [PubMed]
- Pan, Q.; Angelina, A.; Marrone, M.; Stark, W.J.; Akpek, E.K. Autologous serum eye drops for dry eye. Cochrane Database Syst. Rev. 2017, 2, CD009327. [Google Scholar] [CrossRef] [PubMed]
- Marks, D.C.; van der Meer, P.F. Biomedical Excellence for Safer Transfusion (BEST) Collaborative Serum eye drops: A survey of international production methods. Vox Sang. 2017, 112, 310–317. [Google Scholar] [CrossRef] [PubMed]
- Van der Meer, P.F.; Seghatchian, J.; Marks, D.C. Quality standards, safety and efficacy of blood-derived serum eye drops: A review. Transfus. Apher. Sci. 2016, 54, 164–167. [Google Scholar] [CrossRef] [PubMed]
- Ralph, R.A.; Doane, M.G.; Dohlman, C.H. Clinical experience with a mobile ocular perfusion pump. Arch. Ophthalmol. 1975, 93, 1039–1043. [Google Scholar] [CrossRef] [PubMed]
- Fox, R.I.; Chan, R.; Michelson, J.B.; Belmont, J.B.; Michelson, P.E. Beneficial effect of artificial tears made with autologous serum in patients with keratoconjunctivitis sicca. Arthritis Rheumatol. 1984, 27, 459–461. [Google Scholar] [CrossRef]
- Tsubota, K.; Goto, E.; Fujita, H.; Ono, M.; Inoue, H.; Saito, I.; Shimmura, S. Treatment of dry eye by autologous serum application in Sjögren’s syndrome. Br. J. Ophthalmol. 1999, 83, 390–395. [Google Scholar] [CrossRef] [PubMed]
- Tsubota, K.; Goto, E.; Shimmura, S.; Shimazaki, J. Treatment of persistent corneal epithelial defect by autologous serum application. Ophthalmology 1999, 106, 1984–1989. [Google Scholar] [CrossRef]
- Geerling, G.; Maclennan, S.; Hartwig, D. Autologous serum eye drops for ocular surface disorders. Br. J. Ophthalmol. 2004, 88, 1467–1474. [Google Scholar] [CrossRef] [PubMed]
- Lee, J.H.; Kim, M.J.; Ha, S.W.; Kim, H.K. Autologous platelet-rich plasma eye drops in the treatment of recurrent corneal erosions. Korean J. Ophthalmol. 2016, 30, 101–107. [Google Scholar] [CrossRef] [PubMed]
- Bradley, J.C.; Bradley, R.H.; McCartney, D.L.; Mannis, M.J. Serum growth factor analysis in dry eye syndrome. Clin. Exp. Ophthalmol. 2008, 36, 717–720. [Google Scholar] [CrossRef] [PubMed]
- Yamada, C.; King, K.E.; Ness, P.M. Autologous serum eyedrops: Literature review and implications for transfusion medicine specialists. Transfusion 2008, 48, 1245–1255. [Google Scholar] [CrossRef] [PubMed]
- Maclennan, S.; Hartwig, D.; Geerling, G. Experiences with a centralized national service for autologous serum eyedrops in England. Ophthalmologe 2008, 105, 639–643. [Google Scholar] [CrossRef] [PubMed]
- Partal, A.; Scott, E. Low-cost protocol for the production of autologous serum eye drops by blood collection and processing centres for the treatment of ocular surface diseases. Transfus. Med. 2011, 21, 271–277. [Google Scholar] [CrossRef] [PubMed]
- Liu, L.; Hartwig, D.; Harloff, S.; Herminghaus, P.; Wedel, T.; Geerling, G. An optimised protocol for the production of autologous serum eyedrops. Graefes Arch. Clin. Exp. Ophthalmol. 2005, 243, 706–714. [Google Scholar] [CrossRef] [PubMed]
- Yoon, K.-C.; Heo, H.; Im, S.-K.; You, I.-C.; Kim, Y.-H.; Park, Y.-G. Comparison of autologous serum and umbilical cord serum eye drops for dry eye syndrome. Am. J. Ophthalmol. 2007, 144, 86–92. [Google Scholar] [CrossRef] [PubMed]
- Cho, Y.K.; Huang, W.; Kim, G.Y.; Lim, B.S. Comparison of autologous serum eye drops with different diluents. Curr. Eye Res. 2013, 38, 9–17. [Google Scholar] [CrossRef] [PubMed]
- Jones, L.; Downie, L.E.; Korb, D.; Benitez-Del-Castillo, J.M.; Dana, R.; Deng, S.X.; Dong, P.N.; Geerling, G.; Hida, R.Y.; Liu, Y.; et al. TFOS DEWS II management and therapy report. Ocul. Surf. 2017, 15, 575–628. [Google Scholar] [CrossRef] [PubMed]
- Kunz, M.; Ibrahim, S.M. Cytokines and cytokine profiles in human autoimmune diseases and animal models of autoimmunity. Mediat. Inflamm. 2009, 2009, 979258. [Google Scholar] [CrossRef] [PubMed]
- Wang, H.-L.; Avila, G. Platelet rich plasma: Myth or reality? Eur. J. Dent. 2007, 1, 192–194. [Google Scholar] [PubMed]
- Anitua, E.; Andia, I.; Ardanza, B.; Nurden, P.; Nurden, A.T. Autologous platelets as a source of proteins for healing and tissue regeneration. Thromb. Haemost. 2004, 91, 4–15. [Google Scholar] [CrossRef] [PubMed]
- Alio, J.L.; Rodriguez, A.E.; WróbelDudzińska, D. Eye platelet-rich plasma in the treatment of ocular surface disorders. Curr. Opin. Ophthalmol. 2015, 26, 325–332. [Google Scholar] [CrossRef] [PubMed]
- Parrish, W.R.; Roides, B.; Hwang, J.; Mafilios, M.; Story, B.; Bhattacharyya, S. Normal platelet function in platelet concentrates requires non-platelet cells: A comparative in vitro evaluation of leucocyte-rich (type 1a) and leucocyte-poor (type 3b) platelet concentrates. BMJ Open Sport Exerc. Med. 2016, 2, e000071. [Google Scholar] [CrossRef] [PubMed]
- Kobayashi, Y.; Saita, Y.; Nishio, H.; Ikeda, H.; Takazawa, Y.; Nagao, M.; Takaku, T.; Komatsu, N.; Kaneko, K. Leukocyte concentration and composition in platelet-rich plasma (PRP) influences the growth factor and protease concentrations. J. Orthop. Sci. 2016, 21, 683–689. [Google Scholar] [CrossRef] [PubMed]
- Riestra, A.C.; Alonso-Herreros, J.M.; Merayo-Lloves, J. Platelet rich plasma in ocular surface. Arch. Soc. Esp. Oftalmol. 2016, 91, 475–490. [Google Scholar] [CrossRef] [PubMed]
- Merayo-Lloves, J.; Sanchez-Avila, R.M.; Riestra, A.C.; Anitua, E.; Begoña, L.; Orive, G.; Fernandez-Vega, L. Safety and efficacy of autologous plasma rich in growth factors eye drops for the treatment of evaporative dry eye. Ophthalmic Res. 2016, 56, 68–73. [Google Scholar] [CrossRef] [PubMed]
- Sanchez-Avila, R.M.; Merayo-Lloves, J.; Riestra, A.C.; Fernandez-Vega Cueto, L.; Anitua, E.; Begoña, L.; Muruzabal, F.; Orive, G. Treatment of patients with neurotrophic keratitis stages 2 and 3 with plasma rich in growth factors (PRGF-Endoret) eye-drops. Int. Ophthalmol. 2017. [Google Scholar] [CrossRef] [PubMed]
- Riestra, A.C.; Vazquez, N.; Chacon, M.; Berisa, S.; Sanchez-Avila, R.M.; Orive, G.; Anitua, E.; Meana, A.; Merayo-Lloves, J. Autologous method for ex vivo expansion of human limbal epithelial progenitor cells based on plasma rich in growth factors technology. Ocul. Surf. 2017, 15, 248–256. [Google Scholar] [CrossRef] [PubMed]
- López-Plandolit, S.; Morales, M.-C.; Freire, V.; Etxebarría, J.; Durán, J.A. Plasma rich in growth factors as a therapeutic agent for persistent corneal epithelial defects. Cornea 2010, 29, 843–848. [Google Scholar] [CrossRef] [PubMed]
- Yoon, K.C. Use of umbilical cord serum in ophthalmology. Chonnam Med. J. 2014, 50, 82–85. [Google Scholar] [CrossRef] [PubMed]
- Sharma, N.; Goel, M.; Velpandian, T.; Titiyal, J.S.; Tandon, R.; Vajpayee, R.B. Evaluation of umbilical cord serum therapy in acute ocular chemical burns. Invest. Ophthalmol. Vis. Sci. 2011, 52, 1087–1092. [Google Scholar] [CrossRef] [PubMed]
- Joe, A.W.; Gregory-Evans, K. Mesenchymal stem cells and potential applications in treating ocular disease. Curr. Eye Res. 2010, 35, 941–952. [Google Scholar] [CrossRef] [PubMed]
- Zhang, L.; Coulson-Thomas, V.J.; Ferreira, T.G.; Kao, W.W.Y. Mesenchymal stem cells for treating ocular surface diseases. BMC Ophthalmol. 2015, 15, 155. [Google Scholar] [CrossRef] [PubMed]
- Dhamodaran, K.; Subramani, M.; Ponnalagu, M.; Shetty, R.; Das, D. Ocular stem cells: A status update! Stem Cell Res. Ther. 2014, 5, 56. [Google Scholar] [CrossRef] [PubMed]
- Sivan, P.P.; Syed, S.; Mok, P.-L.; Higuchi, A.; Murugan, K.; Alarfaj, A.A.; Munusamy, M.A.; Awang Hamat, R.; Umezawa, A.; Kumar, S. Stem cell therapy for treatment of ocular disorders. Stem Cells Int. 2016, 2016, 8304879. [Google Scholar] [CrossRef] [PubMed]
- Yao, L.; Bai, H. Review: Mesenchymal stem cells and corneal reconstruction. Mol. Vis. 2013, 19, 2237–2243. [Google Scholar] [PubMed]
- Dominici, M.; Le Blanc, K.; Mueller, I.; Slaper-Cortenbach, I.; Marini, F.; Krause, D.; Deans, R.; Keating, A.; Prockop, D.; Horwitz, E. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 2006, 8, 315–317. [Google Scholar] [CrossRef] [PubMed]
- Galipeau, J.; Krampera, M.; Barrett, J.; Dazzi, F.; Deans, R.J.; DeBruijn, J.; Dominici, M.; Fibbe, W.E.; Gee, A.P.; Gimble, J.M.; et al. International Society for Cellular Therapy perspective on immune functional assays for mesenchymal stromal cells as potency release criterion for advanced phase clinical trials. Cytotherapy 2016, 18, 151–159. [Google Scholar] [CrossRef] [PubMed]
- Ankrum, J.A.; Ong, J.F.; Karp, J.M. Mesenchymal stem cells: Immune evasive, not immune privileged. Nat. Biotechnol. 2014, 32, 252–260. [Google Scholar] [CrossRef] [PubMed]
- Wang, Q.; Yang, Q.; Wang, Z.; Tong, H.; Ma, L.; Zhang, Y.; Shan, F.; Meng, Y.; Yuan, Z. Comparative analysis of human mesenchymal stem cells from fetal-bone marrow, adipose tissue, and Warton’s jelly as sources of cell immunomodulatory therapy. Hum. Vaccin. Immunother. 2016, 12, 85–96. [Google Scholar] [CrossRef] [PubMed]
- Mattar, P.; Bieback, K. Comparing the Immunomodulatory Properties of Bone Marrow, Adipose Tissue, and Birth-Associated Tissue Mesenchymal Stromal Cells. Front. Immunol. 2015, 6, 560. [Google Scholar] [CrossRef] [PubMed]
- Sánchez-Abarca, L.I.; Hernández-Galilea, E.; Lorenzo, R.; Herrero, C.; Velasco, A.; Carrancio, S.; Caballero-Velázquez, T.; Rodríguez-Barbosa, J.I.; Parrilla, M.; Del Cañizo, C.; et al. Human bone marrow stromal cells differentiate into corneal tissue and prevent ocular graft-versus-host disease in mice. Cell Transpl. 2015, 24, 2423–2433. [Google Scholar] [CrossRef] [PubMed]
- Konala, V.B.R.; Mamidi, M.K.; Bhonde, R.; Das, A.K.; Pochampally, R.; Pal, R. The current landscape of the mesenchymal stromal cell secretome: A new paradigm for cell-free regeneration. Cytotherapy 2016, 18, 13–24. [Google Scholar] [CrossRef] [PubMed]
- Murphy, M.B.; Moncivais, K.; Caplan, A.I. Mesenchymal stem cells: Environmentally responsive therapeutics for regenerative medicine. Exp. Mol. Med. 2013, 45, e54. [Google Scholar] [CrossRef] [PubMed]
- Hsiao, S.T.-F.; Asgari, A.; Lokmic, Z.; Sinclair, R.; Dusting, G.J.; Lim, S.Y.; Dilley, R.J. Comparative analysis of paracrine factor expression in human adult mesenchymal stem cells derived from bone marrow, adipose, and dermal tissue. Stem Cells Dev. 2012, 21, 2189–2203. [Google Scholar] [CrossRef] [PubMed]
- Li, C.; Wu, X.; Tong, J.; Yang, X.; Zhao, J.; Zheng, Q.; Zhao, G.; Ma, Z. Comparative analysis of human mesenchymal stem cells from bone marrow and adipose tissue under xeno-free conditions for cell therapy. Stem Cell Res. Ther. 2015, 6, 55. [Google Scholar] [CrossRef] [PubMed]
- Ghazaryan, E.; Zhang, Y.; He, Y.; Liu, X.; Li, Y.; Xie, J.; Su, G. Mesenchymal stem cells in corneal neovascularization: Comparison of different application routes. Mol. Med. Rep. 2016, 14, 3104–3112. [Google Scholar] [CrossRef] [PubMed]
- Veréb, Z.; Póliska, S.; Albert, R.; Olstad, O.K.; Boratkó, A.; Csortos, C.; Moe, M.C.; Facskó, A.; Petrovski, G. Role of human corneal stroma-derived mesenchymal-like stem cells in corneal immunity and wound healing. Sci. Rep. 2016, 6, 26227. [Google Scholar] [CrossRef] [PubMed]
- Li, G.-G.; Zhu, Y.-T.; Xie, H.-T.; Chen, S.-Y.; Tseng, S.C.G. Mesenchymal stem cells derived from human limbal niche cells. Invest. Ophthalmol. Vis. Sci. 2012, 53, 5686–5697. [Google Scholar] [CrossRef] [PubMed]
- Li, F.; Zhao, S.-Z. Control of cross talk between angiogenesis and inflammation by mesenchymal stem cells for the treatment of ocular surface diseases. Stem Cells Int. 2016, 2016, 7961816. [Google Scholar] [CrossRef] [PubMed]
- Ma, S.; Xie, N.; Li, W.; Yuan, B.; Shi, Y.; Wang, Y. Immunobiology of mesenchymal stem cells. Cell Death Differ. 2014, 21, 216–225. [Google Scholar] [CrossRef] [PubMed]
- Glenn, J.D.; Whartenby, K.A. Mesenchymal stem cells: Emerging mechanisms of immunomodulation and therapy. World J. Stem Cells 2014, 6, 526–539. [Google Scholar] [CrossRef] [PubMed]
- Spees, J.L.; Lee, R.H.; Gregory, C.A. Mechanisms of mesenchymal stem/stromal cell function. Stem Cell Res. Ther. 2016, 7, 125. [Google Scholar] [CrossRef] [PubMed]
- Lavoie, J.R.; Rosu-Myles, M. Uncovering the secretes of mesenchymal stem cells. Biochimie 2013, 95, 2212–2221. [Google Scholar] [CrossRef] [PubMed]
- Makridakis, M.; Roubelakis, M.G.; Vlahou, A. Stem cells: Insights into the secretome. Biochim. Biophys. Acta 2013, 1834, 2380–2384. [Google Scholar] [CrossRef] [PubMed]
- Kupcova Skalnikova, H. Proteomic techniques for characterisation of mesenchymal stem cell secretome. Biochimie 2013, 95, 2196–2211. [Google Scholar] [CrossRef] [PubMed]
- Phinney, D.G.; Pittenger, M.F. Concise Review: MSC-derived exosomes for cell-free therapy. Stem Cells 2017, 35, 851–858. [Google Scholar] [CrossRef] [PubMed]
- Screven, R.; Kenyon, E.; Myers, M.J.; Yancy, H.F.; Skasko, M.; Boxer, L.; Bigley, E.C.; Borjesson, D.L.; Zhu, M. Immunophenotype and gene expression profile of mesenchymal stem cells derived from canine adipose tissue and bone marrow. Vet. Immunol. Immunopathol. 2014, 161, 21–31. [Google Scholar] [CrossRef] [PubMed]
- Coulson-Thomas, V.J.; Coulson-Thomas, Y.M.; Gesteira, T.F.; Kao, W.W.-Y. Extrinsic and intrinsic mechanisms by which mesenchymal stem cells suppress the immune system. Ocul. Surf. 2016, 14, 121–134. [Google Scholar] [CrossRef] [PubMed]
- Lener, T.; Gimona, M.; Aigner, L.; Börger, V.; Buzas, E.; Camussi, G.; Chaput, N.; Chatterjee, D.; Court, F.A.; Del Portillo, H.A.; et al. Applying extracellular vesicles based therapeutics in clinical trials—An ISEV position paper. J. Extracell. Vesicles 2015, 4, 30087. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kim, J.; Hematti, P. Mesenchymal stem cell-educated macrophages: A novel type of alternatively activated macrophages. Exp. Hematol. 2009, 37, 1445–1453. [Google Scholar] [CrossRef] [PubMed]
- Cao, W.; Cao, K.; Cao, J.; Wang, Y.; Shi, Y. Mesenchymal stem cells and adaptive immune responses. Immunol. Lett. 2015, 168, 147–153. [Google Scholar] [CrossRef] [PubMed]
- Gazdic, M.; Volarevic, V.; Arsenijevic, N.; Stojkovic, M. Mesenchymal stem cells: A friend or foe in immune-mediated diseases. Stem Cell Rev. 2015, 11, 280–287. [Google Scholar] [CrossRef] [PubMed]
- Aluri, H.S.; Samizadeh, M.; Edman, M.C.; Hawley, D.R.; Armaos, H.L.; Janga, S.R.; Meng, Z.; Sendra, V.G.; Hamrah, P.; Kublin, C.L.; et al. Delivery of bone marrow-derived mesenchymal stem cells improves tear production in a mouse model of Sjögren’s syndrome. Stem Cells Int. 2017, 2017, 3134543. [Google Scholar] [CrossRef] [PubMed]
- Lee, M.J.; Ko, A.Y.; Ko, J.H.; Lee, H.J.; Kim, M.K.; Wee, W.R.; Khwarg, S.I.; Oh, J.Y. Mesenchymal stem/stromal cells protect the ocular surface by suppressing inflammation in an experimental dry eye. Mol. Ther. 2015, 23, 139–146. [Google Scholar] [CrossRef] [PubMed]
- Ljubimov, A.V.; Saghizadeh, M. Progress in corneal wound healing. Prog. Retin. Eye Res. 2015, 49, 17–45. [Google Scholar] [CrossRef] [PubMed]
- Beyazyıldız, E.; Pınarlı, F.A.; Beyazyıldız, O.; Hekimoğlu, E.R.; Acar, U.; Demir, M.N.; Albayrak, A.; Kaymaz, F.; Sobacı, G.; Delibaşı, T. Efficacy of topical mesenchymal stem cell therapy in the treatment of experimental dry eye syndrome model. Stem Cells Int. 2014, 2014, 250230. [Google Scholar] [CrossRef] [PubMed]
- Weng, J.; He, C.; Lai, P.; Luo, C.; Guo, R.; Wu, S.; Geng, S.; Xiangpeng, A.; Liu, X.; Du, X. Mesenchymal stromal cells treatment attenuates dry eye in patients with chronic graft-versus-host disease. Mol. Ther. 2012, 20, 2347–2354. [Google Scholar] [CrossRef] [PubMed]
- Villatoro, A.J.; Fernández, V.; Claros, S.; Rico-Llanos, G.A.; Becerra, J.; Andrades, J.A. Use of adipose-derived mesenchymal stem cells in keratoconjunctivitis sicca in a canine model. Biomed. Res. Int. 2015, 2015, 527926. [Google Scholar] [CrossRef] [PubMed]
- Bittencourt, M.K.W.; Barros, M.A.; Martins, J.F.P.; Vasconcellos, J.P.C.; Morais, B.P.; Pompeia, C.; Bittencourt, M.D.; Evangelho, K.D.S.; Kerkis, I.; Wenceslau, C.V. Allogeneic mesenchymal stem cell transplantation in dogs with keratoconjunctivitis sicca. Cell Med. 2016, 8, 63–77. [Google Scholar] [CrossRef] [PubMed]
- Kizilay Mancini, O.; Shum-Tim, D.; Stochaj, U.; Correa, J.A.; Colmegna, I. Age, atherosclerosis and type 2 diabetes reduce human mesenchymal stromal cell-mediated T-cell suppression. Stem Cell Res. Ther. 2015, 6, 140. [Google Scholar] [CrossRef] [PubMed]
- Escacena, N.; Quesada-Hernández, E.; Capilla-Gonzalez, V.; Soria, B.; Hmadcha, A. Bottlenecks in the Efficient Use of Advanced Therapy Medicinal Products Based on Mesenchymal Stromal Cells. Stem Cells Int. 2015, 2015, 895714. [Google Scholar] [CrossRef] [PubMed]
- Schimke, M.M.; Marozin, S.; Lepperdinger, G. Patient-Specific Age: The other side of the coin in advanced mesenchymal stem cell therapy. Front. Physiol. 2015, 6, 362. [Google Scholar] [CrossRef] [PubMed]
- Lin, K.-J.; Loi, M.-X.; Lien, G.-S.; Cheng, C.-F.; Pao, H.-Y.; Chang, Y.-C.; Ji, A.T.-Q.; Ho, J.H.-C. Topical administration of orbital fat-derived stem cells promotes corneal tissue regeneration. Stem Cell Res. Ther. 2013, 4, 72. [Google Scholar] [CrossRef] [PubMed]
- Lee, E.J.; Park, H.-W.; Jeon, H.-J.; Kim, H.-S.; Chang, M.-S. Potentiated therapeutic angiogenesis by primed human mesenchymal stem cells in a mouse model of hindlimb ischemia. Regen. Med. 2013, 8, 283–293. [Google Scholar] [CrossRef] [PubMed]
- Anderson, J.D.; Johansson, H.J.; Graham, C.S.; Vesterlund, M.; Pham, M.T.; Bramlett, C.S.; Montgomery, E.N.; Mellema, M.S.; Bardini, R.L.; Contreras, Z.; et al. Comprehensive proteomic analysis of mesenchymal stem cell exosomes reveals modulation of angiogenesis via nuclear factor-kappaB signaling. Stem Cells 2016, 34, 601–613. [Google Scholar] [CrossRef] [PubMed]
- Oh, J.Y.; Kim, M.K.; Shin, M.S.; Wee, W.R.; Lee, J.H. Cytokine secretion by human mesenchymal stem cells cocultured with damaged corneal epithelial cells. Cytokine 2009, 46, 100–103. [Google Scholar] [CrossRef] [PubMed]
- Katsuda, T.; Kosaka, N.; Takeshita, F.; Ochiya, T. The therapeutic potential of mesenchymal stem cell-derived extracellular vesicles. Proteomics 2013, 13, 1637–1653. [Google Scholar] [CrossRef] [PubMed]
- Tran, C.; Damaser, M.S. Stem cells as drug delivery methods: Application of stem cell secretome for regeneration. Adv. Drug Deliv. Rev. 2015, 82–83, 1–11. [Google Scholar] [CrossRef] [PubMed]
- Baiula, M.; Spampinato, S. Mesenchymal stem cell secretome to control inflammation in allergic conjunctivitis. Eye Sci. 2015, 30, 140–142. [Google Scholar] [CrossRef] [PubMed]
- Bermudez, M.A.; Sendon-Lago, J.; Eiro, N.; Treviño, M.; Gonzalez, F.; Yebra-Pimentel, E.; Giraldez, M.J.; Macia, M.; Lamelas, M.L.; Saa, J.; et al. Corneal epithelial wound healing and bactericidal effect of conditioned medium from human uterine cervical stem cells. Invest. Ophthalmol. Vis. Sci. 2015, 56, 983–992. [Google Scholar] [CrossRef] [PubMed]
- Kim, T.-H.; Park, Y.-W.; Ahn, J.-S.; Ahn, J.-T.; Kim, S.-E.; Jeong, M.-B.; Seo, M.-S.; Kang, K.-S.; Seo, K.-M. Effects of conditioned media from human amniotic epithelial cells on corneal alkali injuries in rabbits. J. Vet. Sci. 2013, 14, 61–67. [Google Scholar] [CrossRef] [PubMed]
- Su, W.; Wan, Q.; Huang, J.; Han, L.; Chen, X.; Chen, G.; Olsen, N.; Zheng, S.G.; Liang, D. Culture medium from TNF-α-stimulated mesenchymal stem cells attenuates allergic conjunctivitis through multiple antiallergic mechanisms. J. Allergy Clin. Immunol. 2015, 136, 423–432. [Google Scholar] [CrossRef] [PubMed]
Component | Tear | AS | PRP | UCS |
---|---|---|---|---|
pH | 7.4 | 7.4 | 6.61–7.26 | 7.4 |
Osmolarity | 298–300 | 296 | 296 | 296 |
Water (%) | 98 | 91 | -- | -- |
Albumin (g/dL) | 0.39 | 4–5.3 | -- | -- |
Globulins (g/dL) | 0.27 | 2.3 | -- | -- |
EGF (ng/mL) | 0.2–0.3 | 0.1–0.2 | 0.27–4.9 | 0.5 |
TGF-β (ng/mL) | 2–10 | 6–33 | 6.4–67.3 | 57 |
NGF (pg/mL) | 107.5–468 | 54–401 | 37.7 | 730 |
IGF-1 (ng/mL) | 75.5–157 | 375 | 93.5 | 230 |
PDGF (ng/mL) | 1.33 | 15–17 | 13–86 | -- |
VEGF (pg/mL) | -- | 34.7–160 | 60–124 | -- |
Vitamin A (ng/mL) | 16 | 372 | -- | 231 |
Vitamin C (mg/mL) | 0.117 | 0.02 | -- | -- |
SP (pg/mL) | 69.8–157 | 71–169 | -- | 245 |
Lysozyme (mg/mL) | 1.4 | 6 | -- | 6 |
Surface IgA (µg/mL) | 1190 | 2 | -- | -- |
Fibronectin (µg/mL) | 21 | 30–205 | 28.9–31.1 | -- |
Lactoferrin (ng/mL) | 1650 | 266 | -- | -- |
Calcium (mmol/L) | 0.3–2 | 2.5 | -- | -- |
Potassium (mmol/L) | 26–42 | 4.5 | -- | -- |
Sodium (mmol/L) | 120–170 | 140 | -- | -- |
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Villatoro, A.J.; Fernández, V.; Claros, S.; Alcoholado, C.; Cifuentes, M.; Merayo-Lloves, J.; Andrades, J.A.; Becerra, J. Regenerative Therapies in Dry Eye Disease: From Growth Factors to Cell Therapy. Int. J. Mol. Sci. 2017, 18, 2264. https://doi.org/10.3390/ijms18112264
Villatoro AJ, Fernández V, Claros S, Alcoholado C, Cifuentes M, Merayo-Lloves J, Andrades JA, Becerra J. Regenerative Therapies in Dry Eye Disease: From Growth Factors to Cell Therapy. International Journal of Molecular Sciences. 2017; 18(11):2264. https://doi.org/10.3390/ijms18112264
Chicago/Turabian StyleVillatoro, Antonio J., Viviana Fernández, Silvia Claros, Cristina Alcoholado, Manuel Cifuentes, Jesús Merayo-Lloves, José A. Andrades, and José Becerra. 2017. "Regenerative Therapies in Dry Eye Disease: From Growth Factors to Cell Therapy" International Journal of Molecular Sciences 18, no. 11: 2264. https://doi.org/10.3390/ijms18112264