International Journal of Stem Cells

Korean Society for Stem Cell Research (한국줄기세포학회)
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Evaluation of the Potential Effects of Retinol and Alginate/Gelatin-Based Scaffolds on Differentiation Capacity of Mouse Mesenchymal Stem Cells (MSCs) into Retinal Cells

  • Mahtab Haghighat (Department of Biology, Science and Research Branch, Islamic Azad University) ;
  • Alireza Iranbakhsh (Department of Biology, Science and Research Branch, Islamic Azad University) ;
  • Javad Baharara (Department of Biology, Applied Biology Research Center, Mashhad Branch, Islamic Azad University) ;
  • Mostafa Ebadi (Department of Biology, Damghan Branch, Islamic Azad University) ;
  • Fattah Sotoodehnejadnematalahia (Department of Biology, Science and Research Branch, Islamic Azad University)
  • Received : 2021.03.31
  • Accepted : 2021.09.08
  • Published : 2022.05.30
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Abstract

Background and Objectives: Retinal stem cells (RSCs) resided in ciliary epithelium have shown to possess a high capacity to self-renew and differentiate into retinal cells. RSCs could be induced to differentiate when they are exposed to stimuli like natural compounds and suitable contexts such as biomaterials. The aim of this study was to examine the effects of Retinol and alginate/gelatin-based scaffolds on differentiation potential of mesenchymal stem cells (MSCs) originated from mouse ciliary epithelium. Methods and Results: MSCs were extracted from mouse ciliary epithelium, and their identity was verified by detecting specific surface antigens. To provide a three-dimensional in vitro culture system, 2% alginate, 0.5% gelatin and the mixed alginate-gelatin hydrogels were fabricated and checked by SEM. Retinol treatment was performed on MSCs expanded on alginate/gelatin hydrogels and the survival rate and the ability of MSCs to differentiate were examined through measuring expression alterations of retina-specific genes by ICC and qPCR. The cell population isolated from ciliary epithelium contained more than 93.4% cells positive for MSC-specific marker CD105. Alginate/gelatin scaffolds showed to provide an acceptable viability (over 70%) for MSC cultures. Retinol treatment could induce a high expression of rhodopsin protein in MSCs expanded in alginate and alginate-gelatin mixtures. An elevated presentation of Nestin, RPE65 and Rhodopsin genes was detected in retinol-treated cultures expanded on alginate and alginate-gelatin scaffolds. Conclusions: The results presented here elucidate that retinol treatment of MSCs grown on alginate scaffolds would promote the mouse ciliary epithelium-derived MSCs to differentiate towards retinal neurons.

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References

  1. Ramachandra Rao S, Fliesler SJ. Cholesterol homeostasis in the vertebrate retina: biology and pathobiology. J Lipid Res 2021;62:100057
  2. Kha CX, Guerin DJ, Tseng KA. Studying in vivo retinal progenitor cell proliferation in Xenopus laevis. Methods Mol Biol 2020;2092:19-33
  3. Angileri KM, Gross JM. dnmt1 function is required to maintain retinal stem cells within the ciliary marginal zone of the zebrafish eye. Sci Rep 2020;10:11293
  4. Centanin L, Hoeckendorf B, Wittbrodt J. Fate restriction and multipotency in retinal stem cells. Cell Stem Cell 2011;9:553-562
  5. Tang X, Gao J, Jia X, Zhao W, Zhang Y, Pan W, He J. Bipotent progenitors as embryonic origin of retinal stem cells. J Cell Biol 2017;216:1833-1847
  6. Eymann J, Salomies L, Macri S, Di-Poi N. Variations in the proliferative activity of the peripheral retina correlate with postnatal ocular growth in squamate reptiles. J Comp Neurol 2019;527:2356-2370
  7. Jorstad NL, Wilken MS, Todd L, Finkbeiner C, Nakamura P, Radulovich N, Hooper MJ, Chitsazan A, Wilkerson BA, Rieke F, Reh TA. STAT signaling modifies Ascl1 chromatin binding and limits neural regeneration from muller glia in adult mouse retina. Cell Rep 2020;30:2195-2208.e5
  8. Aladdad AM, Kador KE. Adult stem cells, tools for repairing the retina. Curr Ophthalmol Rep 2019;7:21-29
  9. Bammidi S, Bali P, Kalra J, Anand A. Transplantation efficacy of human ciliary epithelium cells from fetal eye and Lin-ve stem cells from umbilical cord blood in the murine retinal degeneration model of laser injury. Cell Transplant 2020;29:963689720946031
  10. Tropepe V, Coles BL, Chiasson BJ, Horsford DJ, Elia AJ, McInnes RR, van der Kooy D. Retinal stem cells in the adult mammalian eye. Science 2000;287:2032-2036
  11. Ballios BG, Clarke L, Coles BL, Shoichet MS, Van Der Kooy D. The adult retinal stem cell is a rare cell in the ciliary epithelium whose progeny can differentiate into photoreceptors. Biol Open 2012;1:237-246
  12. Canola K, Angenieux B, Tekaya M, Quiambao A, Naash MI, Munier FL, Schorderet DF, Arsenijevic Y. Retinal stem cells transplanted into models of late stages of retinitis pigmentosa preferentially adopt a glial or a retinal ganglion cell fate. Invest Ophthalmol Vis Sci 2007;48:446-454
  13. MacLaren RE, Pearson RA, MacNeil A, Douglas RH, Salt TE, Akimoto M, Swaroop A, Sowden JC, Ali RR. Retinal repair by transplantation of photoreceptor precursors. Nature 2006;444:203-207
  14. Inoue T, Coles BL, Dorval K, Bremner R, Bessho Y, Kageyama R, Hino S, Matsuoka M, Craft CM, McInnes RR, Tremblay F, Prusky GT, van der Kooy D. Maximizing functional photoreceptor differentiation from adult human retinal stem cells. Stem Cells 2010;28:489-500
  15. Huang L, Chen M, Zhang W, Sun X, Liu B, Ge J. Retinoid acid and taurine promote NeuroD1-induced differentiation of induced pluripotent stem cells into retinal ganglion cells. Mol Cell Biochem 2018;438:67-76
  16. Merhi-Soussi F, Angenieux B, Canola K, Kostic C, Tekaya M, Hornfeld D, Arsenijevic Y. High yield of cells committed to the photoreceptor fate from expanded mouse retinal stem cells. Stem Cells 2006;24:2060-2070
  17. Macheleidt J, Mattern DJ, Fischer J, Netzker T, Weber J, Schroeckh V, Valiante V, Brakhage AA. Regulation and role of fungal secondary metabolites. Annu Rev Genet 2016;50:371-392
  18. Gudas LJ, Wagner JA. Retinoids regulate stem cell differentiation. J Cell Physiol 2011;226:322-330
  19. Lee J, Cuddihy MJ, Kotov NA. Three-dimensional cell culture matrices: state of the art. Tissue Eng Part B Rev 2008;14:61-86
  20. Campuzano S, Pelling AE. Scaffolds for 3D cell culture and cellular agriculture applications derived from non-animal sources. Front Sustain Food Syst 2019;3:38
  21. Pan T, Song W, Cao X, Wang Y. 3D bioplotting of gelatin/alginate scaffolds for tissue engineering: influence of crosslinking degree and pore architecture on physicochemical properties. J Mater Sci Technol 2016;32:889-900
  22. Farokhi M, Shariatzadeh FJ, Solouk A, Mirzadeh H. Alginate based scaffolds for cartilage tissue engineering: a review. Int J Polym Mater Polym Biomater 2020;69:230-247
  23. Zarif ME. A review of chitosan-, alginate-, and gelatin-based biocomposites for bone tissue engineering. Biomater Tissue Eng Bull 2018;5:97-109
  24. Geiger P, Barben M, Grimm C, Samardzija M. Blue light-induced retinal lesions, intraretinal vascular leakage and edema formation in the all-cone mouse retina. Cell Death Dis 2015;6:e1985
  25. Carr AJ, Vugler AA, Hikita ST, Lawrence JM, Gias C, Chen LL, Buchholz DE, Ahmado A, Semo M, Smart MJ, Hasan S, da Cruz L, Johnson LV, Clegg DO, Coffey PJ. Protective effects of human iPS-derived retinal pigment epithelium cell transplantation in the retinal dystrophic rat. PLoS One 2009;4:e8152
  26. Haghighat M, Iranbakhsh A, Baharara J, Ebadi M, Sotoodehnejadnematalahi F. Effect of β-carotene on the differentiation potential of ciliary epithelium-derived MSCs isolated from mouse eyes on alginate-based scaffolds. Exp Eye Res 2021;202:108346
  27. Yu JJ, Azzam DB, Chwa M, Schneider K, Cho JH, Hsiang C, Klassen H, Kenney MC, Yang J. Age-related macular degeneration (AMD) transmitochondrial cybrids protected from cellular damage and death by human retinal progenitor cells (hRPCs). Stem Cells Int 2021;2021:6655372
  28. Del Debbio CB, Peng X, Xiong H, Ahmad I. Adult ciliary epithelial stem cells generate functional neurons and differentiate into both early and late born retinal neurons under non-cell autonomous influences. BMC Neurosci 2013;14:130
  29. Yamamoto N, Hiramatsu N, Ohkuma M, Hatsusaka N, Takeda S, Nagai N, Miyachi EI, Kondo M, Imaizumi K, Horiguchi M, Kubo E, Sasaki H. Novel technique for retinal nerve cell regeneration with electrophysiological functions using human iris-derived iPS cells. Cells 2021;10:743
  30. Notara M, Lentzsch A, Coroneo M, Cursiefen C. The role of limbal epithelial stem cells in regulating corneal (Lymph)angiogenic privilege and the micromilieu of the limbal niche following UV exposure. Stem Cells Int 2018; 2018:8620172
  31. Akrami H, Soheili ZS, Khalooghi K, Ahmadieh H, Rezaie-Kanavi M, Samiei S, Davari M, Ghaderi S, Sanie-Jahromi F. Retinal pigment epithelium culture;a potential source of retinal stem cells. J Ophthalmic Vis Res 2009;4:134-141
  32. Fischer AJ, Reh TA. Transdifferentiation of pigmented epithelial cells: a source of retinal stem cells? Dev Neurosci 2001;23:268-276
  33. Langhe R, Pearson RA. Rebuilding the retina: prospects for Muller glial-mediated self-repair. Curr Eye Res 2020;45:349-360
  34. Khoo HE, Ng HS, Yap WS, Goh HJH, Yim HS. Nutrients for prevention of macular degeneration and eye-related diseases. Antioxidants (Basel) 2019;8:85
  35. Palczewski K. Retinoids for treatment of retinal diseases. Trends Pharmacol Sci 2010;31:284-295
  36. Coles BL, Angenieux B, Inoue T, Del Rio-Tsonis K, Spence JR, McInnes RR, Arsenijevic Y, van der Kooy D. Facile isolation and the characterization of human retinal stem cells. Proc Natl Acad Sci U S A 2004;101:15772-15777
  37. Xu H, Sta Iglesia DD, Kielczewski JL, Valenta DF, Pease ME, Zack DJ, Quigley HA. Characteristics of progenitor cells derived from adult ciliary body in mouse, rat, and human eyes. Invest Ophthalmol Vis Sci 2007;48:1674-1682
  38. Reh TA, Levine EM. Multipotential stem cells and progenitors in the vertebrate retina. J Neurobiol 1998;36:206-220
  39. Bertolotti E, Neri A, Camparini M, Macaluso C, Marigo V. Stem cells as source for retinal pigment epithelium transplantation. Prog Retin Eye Res 2014;42:130-144
  40. Bi Y, Gong M, Zhang X, Zhang X, Jiang W, Zhang Y, Chen J, Liu Y, He TC, Li T. Pre-activation of retinoid signaling facilitates neuronal differentiation of mesenchymal stem cells. Dev Growth Differ 2010;52:419-431
  41. Fawzy El-Sayed KM, Hein D, Dorfer CE. Retinol/inflammation affect stemness and differentiation potential of gingival stem/progenitor cells via Wnt/β-catenin. J Periodontal Res 2019;54:413-423