Skip to main content

Advertisement

Log in

Basic Fibroblast Growth Factor Expression is Implicated in Mesenchymal Stem Cells Response to Light-Induced Retinal Injury

  • Original Research
  • Published:
Cellular and Molecular Neurobiology Aims and scope Submit manuscript

Abstract

Neurotrophic factors are involved in neuroprotection and its expression in mesenchymal stem cells (MSCs) may change during light-induced retinal injury. In this study, neurotrophic factor expression in MSCs was investigated after stimulation by supernatants of homogenized retina (SHR) from normal and light-injured rats. Conditioned media from control MSCs (CM-MSCs), MSCs stimulated by normal SHR (CM-NSHR), and MSCs stimulated by light-injured SHR (CM-ISHR) were examined regarding their ability to prevent degeneration of retinal explants. Basic fibroblast growth factor (bFGF) in MSCs was knockdown by lentivirus-mediated mRNA interference. Transfected MSCs were stimulated by SHR, and retinal preservation was reevaluated in the resultant conditioned media. We detected significant up-regulation of bFGF in CM-ISHR, accompanied by superior retinal neurotrophic effects in CM-ISHR over CM-NSHR and CM-MSCs. Down-regulation of bFGF in MSCs effectively inhibited this protective effect. Adding neutralizing antibody against bFGF to CM-ISHR also induced a similar effect. It is thus concluded that retinal injury may enhance neurotrophic factor expression in MSCs and promote the repair process. bFGF may play a critical role in MSCs’ response to retinal injury.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  • Akiyama K, Chen C, Wang D, Xu X, Qu C, Yamaza T, Cai T, Chen W, Sun L, Shi S (2012) Mesenchymal-stem-cell-induced immunoregulation involves FAS-ligand-/FAS-mediated T cell apoptosis. Cell Stem Cell 10(5):544–555

    Article  PubMed  CAS  Google Scholar 

  • Armulik A, Genove G, Betsholtz C (2011) Pericytes: developmental, physiological, and pathological perspectives, problems, and promises. Dev Cell 21(2):193–215

    Article  PubMed  CAS  Google Scholar 

  • Arriola A, Kiel ME, Shi Y, McKinnon RD (2010) Adjunctive MSCs enhance myelin formation by xenogenic oligodendrocyte precursors transplanted in the retina. Cell Res 20(6):728–731

    Article  PubMed  Google Scholar 

  • Bai L, Lennon DP, Caplan AI, DeChant A, Hecker J, Kranso J, Zaremba A, Miller RH (2012) Hepatocyte growth factor mediates mesenchymal stem cell-induced recovery in multiple sclerosis models. Nat Neurosci 15(6):862–870

    Article  PubMed  CAS  Google Scholar 

  • Balasubramanian S, Thej C, Venugopal P, Priya N, Zakaria Z, Sundarraj S, Majumdar AS (2013) Higher propensity of Wharton’s jelly derived mesenchymal stromal cells towards neuronal lineage in comparison to those derived from adipose and bone marrow. Cell Biol Int 37(5):507–515

    Article  PubMed  CAS  Google Scholar 

  • Bull ND, Johnson TV, Welsapar G, DeKorver NW, Tomarev SI, Martin KR (2011) Use of an adult rat retinal explant model for screening of potential retinal ganglion cell neuroprotective therapies. Invest Ophthalmol Vis Sci 52(6):3309–3320

    Article  PubMed  CAS  Google Scholar 

  • Caplan AI (2008) All MSCs are pericytes? Cell Stem Cell 3(3):229–230

    Article  PubMed  CAS  Google Scholar 

  • Caplan AI, Correa D (2011) The MSC: an injury drugstore. Cell Stem Cell 9(1):11–15

    Article  PubMed  CAS  Google Scholar 

  • Crisan M, Yap S, Casteilla L, Chen CW, Corselli M, Park TS, Andriolo G, Sun B, Zheng B, Zhang L, Norotte C, Teng PN, Traas J, Schugar R, Deasy BM, Badylak S, Buhring HJ, Giacobino JP, Lazzari L, Huard J, Peault B (2008) A perivascular origin for mesenchymal stem cells in multiple human organs. Cell Stem Cell 3(3):301–313

    Article  PubMed  CAS  Google Scholar 

  • Fontaine V, Kinkl N, Sahel J, Dreyfus H, Hicks D (1998) Survival of purified rat photoreceptors in vitro is stimulated directly by fibroblast growth factor-2. J Neurosci 18(23):9662–9672

    PubMed  CAS  Google Scholar 

  • Gregory-Evans K, Chang F, Hodges MD, Gregory-Evans CY (2009) Ex vivo gene therapy using intravitreal injection of GDNF-secreting mouse embryonic stem cells in a rat model of retinal degeneration. Mol Vis 15:962–973

    PubMed  CAS  Google Scholar 

  • Hu F, Wang X, Liang G, Lv L, Zhu Y, Sun B, Xiao Z (2013) Effects of epidermal growth factor and basic fibroblast growth factor on the proliferation and osteogenic and neural differentiation of adipose-derived stem cells. Cell Reprogram 15(3):224–232

    PubMed  CAS  Google Scholar 

  • Inoue Y, Iriyama A, Ueno S, Takahashi H, Kondo M, Tamaki Y, Araie M, Yanagi Y (2007) Subretinal transplantation of bone marrow mesenchymal stem cells delays retinal degeneration in the RCS rat model of retinal degeneration. Exp Eye Res 85(2):234–241

    Article  PubMed  CAS  Google Scholar 

  • Joe AW, Gregory-Evans K (2010) Mesenchymal stem cells and potential applications in treating ocular disease. Curr Eye Res 35(11):941–952

    Article  PubMed  Google Scholar 

  • Joly S, Pernet V, Chemtob S, Di Polo A, Lachapelle P (2007) Neuroprotection in the juvenile rat model of light-induced retinopathy: evidence suggesting a role for FGF-2 and CNTF. Invest Ophthalmol Vis Sci 48(5):2311–2320

    Article  PubMed  Google Scholar 

  • Kamouchi M, Ago T, Kitazono T (2011) Brain pericytes: emerging concepts and functional roles in brain homeostasis. Cell Mol Neurobiol 31(2):175–193

    Article  PubMed  Google Scholar 

  • Kicic A, Shen WY, Wilson AS, Constable IJ, Robertson T, Rakoczy PE (2003) Differentiation of marrow stromal cells into photoreceptors in the rat eye. J Neurosci 23(21):7742–7749

    PubMed  CAS  Google Scholar 

  • Kolomeyer AM, Sugino IK, Zarbin MA (2011) Characterization of conditioned media collected from cultured adult versus fetal retinal pigment epithelial cells. Invest Ophthalmol Vis Sci 52(8):5973–5986

    Article  PubMed  CAS  Google Scholar 

  • Kong P, Xie X, Li F, Liu Y, Lu Y (2013) Placenta mesenchymal stem cell accelerates wound healing by enhancing angiogenesis in diabetic goto-kakizaki (GK) rats. Biochem Biophys Res Commun 438(2):410–419. doi:10.1016/j.bbrc.2013.07.088

    Article  PubMed  CAS  Google Scholar 

  • Li N, Li XR, Yuan JQ (2009) Effects of bone-marrow mesenchymal stem cells transplanted into vitreous cavity of rat injured by ischemia/reperfusion. Graefes Arch Clin Exp Ophthalmol 247(4):503–514

    Article  PubMed  Google Scholar 

  • Li Z, Liu C, Xie Z, Song P, Zhao RC, Guo L, Liu Z, Wu Y (2011) Epigenetic dysregulation in mesenchymal stem cell aging and spontaneous differentiation. PLoS One 6(6):e20526

    Article  PubMed  CAS  Google Scholar 

  • Liu DN, Yin ZQ, Wu N, Wang YH, Chen LF (2009) Rat bone marrow stromal cells express retinal phenotypic markers following different induction protocols. Ophthalmic Res 41(4):186–193

    Article  PubMed  CAS  Google Scholar 

  • Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 25(4):402–408

    Article  PubMed  CAS  Google Scholar 

  • O’Driscoll C, O’Connor J, O’Brien CJ, Cotter TG (2008) Basic fibroblast growth factor-induced protection from light damage in the mouse retina in vivo. J Neurochem 105(2):524–536

    Article  PubMed  Google Scholar 

  • Organisciak DT, Vaughan DK (2010) Retinal light damage: mechanisms and protection. Prog Retin Eye Res 29(2):113–134

    Article  PubMed  Google Scholar 

  • Ramasamy R, Tong CK, Yip WK, Vellasamy S, Tan BC, Seow HF (2012) Basic fibroblast growth factor modulates cell cycle of human umbilical cord-derived mesenchymal stem cells. Cell Prolif 45(2):132–139

    Article  PubMed  CAS  Google Scholar 

  • Saito T, Abe T, Wakusawa R, Sato H, Asai H, Tokita-Ishikawa Y, Nishida K (2009) TrkB-T1 receptors on Muller cells play critical role in brain-derived neurotrophic factor-mediated photoreceptor protection against phototoxicity. Curr Eye Res 34(7):580–588

    Article  PubMed  CAS  Google Scholar 

  • Scheibe F, Klein O, Klose J, Priller J (2012) Mesenchymal stromal cells rescue cortical neurons from apoptotic cell death in an in vitro model of cerebral ischemia. Cell Mol Neurobiol 32(4):567–576

    Article  PubMed  CAS  Google Scholar 

  • Schmittgen TD, Livak KJ (2008) Analyzing real-time PCR data by the comparative C(T) method. Nat Protoc 3(6):1101–1108

    Article  PubMed  CAS  Google Scholar 

  • Sotiropoulou PA, Perez SA, Salagianni M, Baxevanis CN, Papamichail M (2006) Characterization of the optimal culture conditions for clinical scale production of human mesenchymal stem cells. Stem Cells 24(2):462–471

    Article  PubMed  Google Scholar 

  • Tasso R, Gaetani M, Molino E, Cattaneo A, Monticone M, Bachi A, Cancedda R (2012) The role of bFGF on the ability of MSC to activate endogenous regenerative mechanisms in an ectopic bone formation model. Biomaterials 33(7):2086–2096

    Article  PubMed  CAS  Google Scholar 

  • Uccelli A, Laroni A, Freedman MS (2011) Mesenchymal stem cells for the treatment of multiple sclerosis and other neurological diseases. Lancet Neurol 10(7):649–656

    Article  PubMed  CAS  Google Scholar 

  • Valter K, Bisti S, Gargini C, Di Loreto S, Maccarone R, Cervetto L, Stone J (2005) Time course of neurotrophic factor upregulation and retinal protection against light-induced damage after optic nerve section. Invest Ophthalmol Vis Sci 46(5):1748–1754

    Article  PubMed  Google Scholar 

  • Wang S, Lu B, Girman S, Duan J, McFarland T, Zhang QS, Grompe M, Adamus G, Appukuttan B, Lund R (2010) Non-invasive stem cell therapy in a rat model for retinal degeneration and vascular pathology. PLoS One 5(2):e9200

    Article  PubMed  Google Scholar 

  • Wen R, Cheng T, Song Y, Matthes MT, Yasumura D, LaVail MM, Steinberg RH (1998) Continuous exposure to bright light upregulates bFGF and CNTF expression in the rat retina. Curr Eye Res 17(5):494–500

    Article  PubMed  CAS  Google Scholar 

  • Wu J, Huang GT, He W, Wang P, Tong Z, Jia Q, Dong L, Niu Z, Ni L (2012) Basic fibroblast growth factor enhances stemness of human stem cells from the apical papilla. J Endod 38(5):614–622

    Article  PubMed  Google Scholar 

  • Zhang Y, Wang W (2010) Effects of bone marrow mesenchymal stem cell transplantation on light-damaged retina. Invest Ophthalmol Vis Sci 51(7):3742–3748

    Article  PubMed  Google Scholar 

  • Zhang HT, Luo J, Sui LS, Ma X, Yan ZJ, Lin JH, Wang YS, Chen YZ, Jiang XD, Xu RX (2009) Effects of differentiated versus undifferentiated adipose tissue-derived stromal cell grafts on functional recovery after spinal cord contusion. Cell Mol Neurobiol 29(8):1283–1292

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported by grants from the National Natural Science Foundation of China (No. 81271026) and the Innovation Platform Foundation of Fujian Province (No. 2010Y2003).

Conflict of interest

The authors declare that there are no conflicts of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Guoxing Xu.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Xu, W., Wang, X., Xu, G. et al. Basic Fibroblast Growth Factor Expression is Implicated in Mesenchymal Stem Cells Response to Light-Induced Retinal Injury. Cell Mol Neurobiol 33, 1171–1179 (2013). https://doi.org/10.1007/s10571-013-9983-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10571-013-9983-y

Keywords

Navigation