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Protective effects of human umbilical cord blood stem cell intravitreal transplantation against optic nerve injury in rats

  • Basic Science
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Abstract

Background

The majority of studies addressing traumatic optic neuropathy (TON) have focused on drugs, proteins, cytokines, and various surgical techniques. A recent study reported that transplantation of human umbilical cord blood stem cells (hUCBSCs) achieved therapeutic effects on TON, but the exact effects on optic nerve injury are still unknown, and the mechanisms underlying nerve protection remain poorly understood.

Methods

A total of 135 healthy Sprague–Dawley adult rats were randomly assigned to three groups: sham-surgery, model and transplantation, with 45 rats in each group. TON was induced in the model and transplantation groups via optic nerve crush injury. The crush injury was not performed in the sham-surgery group. Seven days after the injury, 106 hUCBSCs were injected into the rat vitreous cavity of transplantation group, and an equal volume of physiological saline was administered to the model and sham-surgery groups. Pathological observation of rat retina tissues was performed by hematoxylin–eosin (H&E) staining at days 3, 7, 14, 21 and 28 post-surgery. The number of retinal ganglion cells (RGCs) and mRNA expression levels of brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) were assessed by the Fluorogold (FG) retrograde labeling and reverse transcriptase–polymerase chain reaction (RT–PCR) methods, respectively.

Results

The number of labeled RGCs and the expression of BDNF and GDNF mRNA obviously increased, and pathological injury was significantly ameliorated in the transplantation group compared to the model group (P < 0.05).

Conclusions

Via intravitreal transplantation, the hUCBSCs resulted in a significant increase in the survival of the RGCs, and improved pathological changes in the rat retina, following TON. The protective mechanism is correlated with the continuous secretion of BDNF and GDNF in vivo of retina in optic nerve injury rats by the transplanted hUCBSCs.

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References

  1. Lagrèze W (2009) Treatment of optic neuropathies—state of the art. Klin Monatsbl Augenheilkd 226:875–880

    Article  PubMed  Google Scholar 

  2. Selhorst JB, Chen Y (2009) The optic nerve. Semin Neurol 29:29–35

    Article  PubMed  Google Scholar 

  3. Wu N, Yin ZQ, Wang Y (2008) Traumatic optic neuropathy therapy: an update of clinical and experimental studies. J Int Med Res 36:883–889

    PubMed  CAS  Google Scholar 

  4. Steinsapir KD (1999) Traumatic optic neuropathy. Curr Opin Ophthalmol 10:340–342

    Article  PubMed  CAS  Google Scholar 

  5. Osborne NN, Chidlow G, Layton CJ, Wood JP, Casson RJ, Melena J (2004) Optic nerve and neuroprotection strategies. Eye 18:1075–1084

    Article  PubMed  CAS  Google Scholar 

  6. Mattson MP (2001) Stem cells as therapeutics for neurodegenerative disorders? Expert Rev Neurother 1:267–273

    Article  PubMed  CAS  Google Scholar 

  7. Knudtzon S (1974) In vitro growth of granulocytic colonies from circulating cells in human cord blood. Blood 43:357–361

    PubMed  CAS  Google Scholar 

  8. Hao QL, Shah AJ, Thiemann FT, Smogorzewska EM, Crooks GM (1995) A functional comparison of CD34 + CD38- cells in cord blood and bone marrow. Blood 86:3745–3753

    PubMed  CAS  Google Scholar 

  9. Bjugstad KB, Redmond DE Jr, Teng YD, Elsworth JD, Roth RH, Blanchard BC, Snyder EY, Sladek JR Jr (2005) Neural stem cells implanted into MPTP-treated monkeys increase the size of endogenous tyrosine hydroxylase-positive cells found in the striatum: a return to control measures. Cell Transplant 14:183–192

    Article  PubMed  Google Scholar 

  10. Haas S, Weidner N, Winkler J (2005) Adult stem cell therapy in stroke. Curr Opin Neurol 18:59–64

    Article  PubMed  Google Scholar 

  11. Garbuzova-Davis S, Willing AE, Saporta S, Bickford PC, Gemma C, Chen N, Sanberg CD, Klasko SK, Borlongan CV, Sanberg PR (2006) Novel cell therapy approaches for brain repair. Prog Brain Res 157:207–222

    Article  PubMed  CAS  Google Scholar 

  12. Peinado-Ramon P, Salvador M, Villegas-Perez MP, Vidal-Sanz M (1996) Effects of axotomy and intraocular administration of NT-4, NT-3, and brain-derived neurotrophic factor on the survival of adult rat retinal ganglion cells. A quantitative in vivo study. Invest Ophthalmol Vis Sci 37:489–500

    PubMed  CAS  Google Scholar 

  13. Wittekind D (2003) Traditional staining for routine diagnostic pathology including the role of tannic acid. 1. Value and limitations of the hematoxylin-eosin stain. Biotech Histochem 78:261–270

    Article  PubMed  CAS  Google Scholar 

  14. Wilhelm H (2004) Traumatic optic neuropathy—the present state. Klin Monatsbl Augenheilkd 221:702–705

    Article  PubMed  CAS  Google Scholar 

  15. Lee AG (2000) Traumatic optic neuropathy. Ophthalmology 107:814

    Article  PubMed  CAS  Google Scholar 

  16. Zapała J (2005) Guidelines for the management of posttraumatic optic nerve neuropathy. Klin Oczna 107:263–265

    PubMed  Google Scholar 

  17. Sieśkiewicz A, Łysoń T, Mariak Z, Rogowski M (2008) Endoscopic decompression of the optic nerve in patients with post-traumatic vision impairment. Klin Oczna 110:155–158

    PubMed  Google Scholar 

  18. Li H, Zhou B, Shi J, Cheng L, Wen W, Xu G (2008) Treatment of traumatic optic neuropathy: our experience of endoscopic optic nerve decompression. J Laryngol Otol 122:1325–1329

    Article  PubMed  CAS  Google Scholar 

  19. Zuo KJ, Shi JB, Wen WP, Chen HX, Zhang XM, Xu G (2009) Transnasal endoscopic optic nerve decompression for traumatic optic neuropathy: analysis of 155 cases. Zhonghua Yi Xue Za Zhi 89:389–392

    PubMed  Google Scholar 

  20. Bojanić I, Golubić Cepulić B (2006) Umbilical cord blood as a source of stem cells. Acta Med Croat 60:215–225

    Google Scholar 

  21. Garbuzova-Davis S, Willing AE, Zigova T, Saporta S, Justen EB, Lane JC, Hudson JE, Chen N, Davis CD, Sanberg PR (2003) Intravenous administration of human umbilical cord blood cells in a mouse model of amyotrophic lateral sclerosis: distribution, migration, and differentiation. J Hematother Stem Cell Res 12:255–270

    Article  PubMed  CAS  Google Scholar 

  22. Newcomb JD, Sanberg PR, Klasko SK, Willing AE (2007) Umbilical cord blood research: current and future perspectives. Cell Transplant 16:151–158

    PubMed  Google Scholar 

  23. Canque B, Camus S, Dalloul A, Kahn E, Yagello M, Dezutter-Dambuyant C, Schmitt D, Schmitt C, Gluckman JC (2000) Characterization of dendritic cell differentiation pathways from cord blood CD34(+)CD7(+)CD45RA(+) hematopoietic progenitor cells. Blood 96:3748–3756

    PubMed  CAS  Google Scholar 

  24. Bacigalupo A, Hows J, Gordon-Smith EC, Gluckman E, Van Lint MT, Congiu M, James DC, Barrett AJ, Gmur J, De Planque MM (1988) Bone marrow transplantation for severe aplastic anemia from donors other than HLA identical siblings: a report of the BMT Working Party. Bone Marrow Transplant 3:531–535

    PubMed  CAS  Google Scholar 

  25. Slater BJ, Mehrabian Z, Guo Y, Hunter A, Bernstein SL (2008) Rodent anterior ischemic optic neuropathy (rAION) induces regional retinal ganglion cell apoptosis with a unique temporal pattern. Invest Ophthalmol Vis Sci 49:3671–3676

    Article  PubMed  Google Scholar 

  26. Dasari VR, Spomar DG, Gondi CS, Sloffer CA, Saving KL, Gujrati M, Rao JS, Dinh DH (2007) Axonal remyelination by cord blood stem cells after spinal cord injury. J Neurotrauma 24:391–410

    Article  PubMed  Google Scholar 

  27. Parrilla-Reverter G, Agudo M, Sobrado-Calvo P, Salinas-Navarro M, Villegas-Perez MP, Vidal-Sanz M (2009) Effects of different neurotrophic factors on the survival of retinal ganglion cells after a complete intraorbital nerve crush injury: a quantitative in vivo study. Exp Eye Res 89:32–41

    Article  PubMed  CAS  Google Scholar 

  28. van Adel BA, Kostic C, Deglon N, Ball AK, Arsenijevic Y (2003) Delivery of ciliary neurotrophic factor via lentiviral-mediated transfer protects axotomized retinal ganglion cells for an extended period of time. Hum Gene Ther 14:103–115

    Article  PubMed  Google Scholar 

  29. Martin KR, Quigley HA, Zack DJ, Levkovitch-Verbin H, Kielczewski J, Valenta D, Baumrind L, Pease ME, Klein RL, Hauswirth WW (2003) Gene therapy with brain-derived neurotrophic factor as a protection: retinal ganglion cells in a rat glaucoma model. Invest Ophthalmol Vis Sci 44:4357–4365

    Article  PubMed  Google Scholar 

  30. Leaver SG, Cui Q, Plant GW, Arulpragasam A, Hisheh S, Verhaagen J, Harvey AR (2006) AAV-mediated expression of CNTF promotes long-term survival and regeneration of adult rat retinal ganglion cells. Gene Ther 13:1328–1341

    Article  PubMed  CAS  Google Scholar 

  31. Kao CH, Chen SH, Chio CC, Lin MT (2008) Human umbilical cord blood-derived CD34+ cells may attenuate spinal cord injury by stimulating vascular endothelial and neurotrophic factors. Shock 29:49–55

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Ophthalmology, Second Xiang Ya Hospital, Central South University, No. 139, Renmin Road, Changsha, Hunan Province, 410011, People’s Republic of China

    Tantai Zhao, Luosheng Tang, Yuehua Li, Fang Fan & Bing Jiang

  2. Department of Ophthalmology, Second People’s Hospital of Yunnan Province, No. 176, Qingnian Road, Kunming, Yunnan Province, 650021, People’s Republic of China

    Yunqin Li

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  1. Tantai Zhao
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  2. Yunqin Li
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  4. Yuehua Li
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  5. Fang Fan
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Correspondence to Luosheng Tang.

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There is no financial relationship with the organization that sponsored the research. The authors have full control of all primary data, and we agree to allow Graefe’s Archive for Clinical and Experimental Ophthalmology to review our data upon request.

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Zhao, T., Li, Y., Tang, L. et al. Protective effects of human umbilical cord blood stem cell intravitreal transplantation against optic nerve injury in rats. Graefes Arch Clin Exp Ophthalmol 249, 1021–1028 (2011). https://doi.org/10.1007/s00417-011-1635-7

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  • DOI: https://doi.org/10.1007/s00417-011-1635-7

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