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Effect of intracameral human cord blood-derived stem cells on lasered rabbit trabecular meshwork

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Abstract

Background

This study aimed to investigate the effect of intracameral human cord blood stem cells on lasered rabbit trabecular meshwork.

Methods

Immediately following diode laser application to the trabecular meshwork, human cord blood stem cells were injected intracamerally, in one eye of 12 albino rabbits. The other eye of ten rabbits was lasered controls and two eyes were normal controls. Rabbits were killed after 4, 8 and 12 weeks.

Results

Lasered control rabbit eyes showed significant disruption of trabecular architecture, loss and pleomorphism of trabecular endothelial cells and progressive narrowing of trabecular spaces till 12 weeks. In contrast, lasered eyes, concurrently injected with human cord blood stem cells, showed relatively preserved endothelial cellularity and structure of the trabecular meshwork, at all time points. Human CD34- and CD44-positive cells were identified in 7/8 eyes treated with stem cells, at 4 and 8 weeks, and 2 of 3 at 12 weeks. Many PKH26-labeled human cord blood cells were visible throughout the trabecular area at 4 weeks. They gradually decreased in number by 8 weeks, and at 12 weeks, they appeared to be oriented along trabecular beams.

Conclusions

There was a relative preservation of cellularity and architecture of the trabecular meshwork in eyes injected with human cord blood stem cells, as compared to lasered control eyes up to 12 weeks, without significant inflammation. This suggests a probable role for such stem cells in eyes with glaucoma, having trabecular dysfunction.

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References

  1. Kingman S (2004) Glaucoma is second leading cause of blindness globally. Bull World Health Organ 82(11):887–888

    PubMed  PubMed Central  Google Scholar 

  2. Coleman AL, Miglior S (2008) Risk factors for glaucoma onset and progression. Surv Ophthalmol 53(Suppl 1):S3–S10

    Article  Google Scholar 

  3. Tektas OY, Lütjen-Drecoll E (2009) Structural changes of the trabecular meshwork in different kinds of glaucoma. Exp Eye Res 88:769–775

    Article  CAS  Google Scholar 

  4. Sihota R, Lakshmaiah NC, Walia KB, Sharma S, Pailoor J, Agarwal HC (2001) The trabecular meshwork in acute and chronic angle closure glaucoma. Indian J Ophthalmol 49:255–259

    CAS  PubMed  Google Scholar 

  5. Tripathi RC (1978) Aqueous outflow pathway in normal and glaucomatous eyes. Br J Ophthalmol 56:157–174

    Article  Google Scholar 

  6. Spencer WH (1985) Glaucoma. In: Spencer WH (ed) Ocular Pathology, An Atlas and Textbook. WB Saunders, Philadelphia, pp 480–547

    Google Scholar 

  7. Alvarado JA, Murphy CG (1992) Outflow obstruction in pigmentary and open angle glaucoma. Arch Ophthalmol 110:1769–1772

    Article  CAS  Google Scholar 

  8. Abu-Hassan DW, Li X, Ryan EI, Acott TS, Kelley MJ (2015) Induced pluripotent stem cells restore function in a human cell loss model of open-angle glaucoma. Stem Cells (Dayton, Ohio) 33(3):751–761. https://doi.org/10.1002/stem.1885

    Article  CAS  Google Scholar 

  9. Manuguerra-Gagné R, Boulos PR, Ammar A, Leblond FA, Krosl G, Pichette V, Lesk MR, Roy DC (2013) Transplantation of mesenchymal stem cells promotes tissue regeneration in a glaucoma model through laser-induced paracrine factor secretion and progenitor cell recruitment. Stem Cells 31:1136–1148

    Article  Google Scholar 

  10. Ding QJ, Zhu W, Cook AC, Anfinson KR, Tucker BA, Kuehn MH (2014) Induction of trabecular meshwork cells from induced pluripotent stem cells. Invest Ophthalmol Vis Sci 55:7065–7072

    Article  Google Scholar 

  11. Zhu W et al (2016) Transplantation of iPSC-derived TM cells rescues glaucoma phenotypes in vivo. Proc Natl Acad Sci USA 113:E3492–E3500

    Article  CAS  Google Scholar 

  12. Roubeix C et al (2015) Intraocular pressure reduction and neuroprotection conferred by bone marrow-derived mesenchymal stem cells in an animal model of glaucoma. Stem Cell Res Therapy 6:177

    Article  Google Scholar 

  13. Snider EJ, Kubelick KP, Tweed K, Kim RK, Li Y, Gao K, Read AT, Emelianov S, Ethier CR (2018) Improving stem cell delivery to the trabecular meshwork using magnetic nanoparticles. Sci Rep 8(1):12251

    Article  CAS  Google Scholar 

  14. Levkovitch-Verbin H, Quigley HA, Martin KR, Valenta D, Baumrind LA, Pease ME (2002) Translimbal laser photocoagulation to the trabecular meshwork as a model of glaucoma in rats. Invest Ophthalmol Vis Sci 43:402–410

    PubMed  Google Scholar 

  15. Keeney M, Chin-Yee I, Weir K, Popma J, Nayar R, Sutherland DR (1998) Single platform flow cytometric absolute CD34+ cell counts based on the ISHAGE guidelines. Int Soc Hematother Graft Eng Cytom 34:61–70

    CAS  Google Scholar 

  16. Johnson TV, Bull ND, Hunt DP, Marina N, Tomarev SI, Martin KR (2010) Neuroprotective effects of intravitreal mesenchymal stem cell transplantation in experimental glaucoma. Invest Ophthalmol Vis Sci 51:2051–2059

    Article  Google Scholar 

  17. Otani A, Dorrell MI, Kinder K, Moreno SK (2004) Rescue of retinal degeneration by intravitreally injected adult bone marrow-derived lineage-negative hematopoietic stem cells. J Clin Invest 114:765–774

    Article  CAS  Google Scholar 

  18. Du Y, Yun H, Yang E, Schuman JS (2013) Stem cells from trabecular meshwork home to TM tissue in vivo. Invest Ophthalmol Vis Sci 54:1450–1459

    Article  CAS  Google Scholar 

  19. Grewal SS, Barker JN, Davies SM, Wagner JE (2003) Unrelated donor hematopoietic cell transplantation: marrow or umbilical cord blood? Blood 101:4233–4244

    Article  CAS  Google Scholar 

  20. Zigova T, Song S, Willing AE, Hudson JE, Newman MB, Saporta S, Sanchez-Ramos J, Sanberg PR (2002) Human umbilical cord blood cells express neural antigens after transplantation into the developing rat brain. Cell Transplant 11:265–274

    Article  Google Scholar 

  21. Hao L, Zhang C, Chen XH, Zou ZM, Zhang X, Kong PY, Liang X, Gao L, Peng XG, Sun AH, Wang QY (2009) Human umbilical cord blood-derived stromal cells suppress xenogeneic immune cell response in vitro. Croat Med J. 50:351–360

    Article  CAS  Google Scholar 

  22. Wang M, Yang Y, Yang D, Luo F, Liang W, Guo S, Xu J (2009) The immunomodulatory activity of human umbilical cord blood-derived mesenchymal stem cells in vitro. Immunology 126:220–232

    Article  CAS  Google Scholar 

  23. Laughlin MJ (2001) Umbilical cord blood for allogeneic transplantation in children and adults. Bone Marrow Transplant 27:1–6

    Article  CAS  Google Scholar 

  24. Jablonska A, Kozlowska H, Markiewicz I, Domanska-Janik K, Lukomska B (2010) Transplantation of neural stem cells derived from human cord blood to the brain of adult and neonatal rats. Acta Neurobiol Exp (Wars) 70:337–350

    Google Scholar 

  25. Gherezghiher T, March WF, Nordquist RE, Koss MC (1986) Laser Induced glaucoma in rabbits. Exp Eye Res 43:885–894

    Article  CAS  Google Scholar 

  26. Wang RF, Schumer RA, Serle JB, Podos SM (1998) A comparison of Argon laser and Diode laser photocoagulation of trabecular meshwork to produce the Glaucoma Monkey Model. J Glaucoma 7:45–49

    Article  CAS  Google Scholar 

  27. Johnson DH (2007) Histologic findings after argon laser trabeculoplasty in glaucomatous eyes. Exp Eye Res 85:557–562

    Article  CAS  Google Scholar 

  28. Koller T, Stürmer J, Remé C, Gloor B (2000) Membrane formation in the chamber angle after failure of argon laser trabeculoplasty: analysis of risk factors. Br J Ophthalmol 84:48–53

    Article  CAS  Google Scholar 

  29. Leow SN, Luu CD, Nizam MHH, Mok PL, Ruhaslizan R, Wong HS, Halim WHWA, Ng MH, Ruszymah BH, Chowdhury SR, Bastion ML, Then KY (2015) Safety and efficacy of human Wharton’s Jelly-derived mesenchymal stem cells therapy for retinal degeneration. PLoS ONE 10:e0128973

    Article  CAS  Google Scholar 

  30. Wagner JE, Barker JN, DeFor TE, Baker KS, Blazar BR, Eide C, Goldman A, Kersey J, Krivit W, MacMillan ML, Orchard PJ, Peters C, Weisdorf DJ, Ramsay NK, Davies SM (2002) Transplantation of unrelated donor umbilical cord blood in 102 patients with malignant and nonmalignant diseases: influence of CD34 cell dose and HLA disparity on treatment-related mortality and survival. Blood 100:1611–1618

    Article  CAS  Google Scholar 

  31. Lin CS, Ning H, Lin G, Lue TF (2012) Is CD34 truly a negative marker for mesenchymal stromal cells? Cytotherapy. 14:1159–1163

    Article  CAS  Google Scholar 

  32. Zhang YJ, Yang YX, Hu MY, Ni QK, Li HG, Miao ZC (2015) Importance of CD44 on umbilical cord mesenchymal stem cells for expansion of hematopoietic cells. Cell Mol Biol (Noisy-le-grand) 61:18–25

    CAS  Google Scholar 

  33. Siqueira RC, Messias A, Messias K, Arcieri RS, Ruiz MA, Souza NF, Martins LC, Jorge R (2015) Quality of life in patients with retinitis pigmentosa submitted to intravitreal use of bone marrow-derived stem cells (Reticell -clinical trial). Stem Cell Res Ther 6:29

    Article  Google Scholar 

  34. Park SS, Bauer G, Abedi M, Pontow S, Panorgias A, Jonnal R, Zawadzki RJ, Werner JS, Nolta J (2014) Intravitreal autologous bone marrow CD34+ cell therapy for ischemic and degenerative retinal disorders: preliminary phase 1 clinical trial findings. Invest Ophthalmol Vis Sci 56:81–89

    Article  Google Scholar 

  35. Srivastava A, Bapat M, Ranade S, Srinivasan V, Murugan P, Manjunath S, Thamaraikannan P, Abraham S (2010) Autologous multiple injections of in vitro expanded autologous bone marrow stem cells for cervical level spinal cord injury—a case report. J Stem Cells Regen Med 6:175–176

    CAS  PubMed  Google Scholar 

  36. Subrammaniyan R, Amalorpavanathan J, Shankar R, Rajkumar M, Baskar S, Manjunath SR, Senthilkumar R, Murugan P, Srinivasan VR, Abraham S (2011) Application of autologous bone marrow mononuclear cells in six patients with advanced chronic critical limb ischemia as a result of diabetes: our experience. Cytotherapy 13:993–999

    Article  CAS  Google Scholar 

  37. Roncarolo MG, Bigler M, Martino S, Ciuti E, Tovo PA, Wagner J (1996) Immune functions of cord blood cells before and after transplantation. J Hematother 5:157–160

    Article  CAS  Google Scholar 

  38. Coulson-Thomas VJ, Gesteira TF, Hascall V, Kao W (2014) Umbilical cord mesenchymal stem cells suppress host rejection: the role of the glycocalyx. J Biol Chem 289:23465–23481

    Article  CAS  Google Scholar 

  39. Rieck B (2003) Unexpected durability of PKH 26 staining on rat adipocytes. Cell Biol Int 27:445–447

    Article  CAS  Google Scholar 

  40. Ishikawa F, Shimazu H, Shultz LD, Fukata M, Nakamura R, Lyons B, Shimoda K, Shimoda S, Kanemaru T, Nakamura K, Ito H, Kaji Y, Perry AC, Harada M (2006) Purified human hematopoietic stem cells contribute to the generation of cardiomyocytes through cell fusion. FASEB J 20:950–952

    Article  CAS  Google Scholar 

  41. Lund RD, Wang S, Lu B et al (2007) Cells isolated from umbilical cord tissue rescue photoreceptors and visual functions in a rodent model of retinal disease. Stem Cells 25:602–611

    Article  CAS  Google Scholar 

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Correspondence to Ramanjit Sihota.

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The authors declare that they have no conflict of interest.

Research involving animals

The study was carried out after clearance from our Institutional Animal Ethics and Stem Cell Ethics Committees. The animals were housed in pathogen-free conditions and treated as per the ARVO statement on the use of animals in ophthalmic and vision research. All applicable international, national and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the 1964 Helsinki declaration and its later amendments.

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Informed consent was obtained from all stem cell donors included in the study.

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Sihota, R., Sen, S., Mohanty, S. et al. Effect of intracameral human cord blood-derived stem cells on lasered rabbit trabecular meshwork. Int Ophthalmol 39, 2757–2766 (2019). https://doi.org/10.1007/s10792-019-01120-w

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