June 2015
Volume 56, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2015
Therapeutic potential of adipose tissue derived mesenchymal stem cells for AMD - migration, trophic anti-angiogenic effects and differentiation
Author Affiliations & Notes
  • Aya Barzelay
    Ophthalmology, Tel Aviv Medical Center, Tel aviv, Israel
    Tel Aviv University, Tel Aviv, Israel
  • Ran Levy
    Ophthalmology, Tel Aviv Medical Center, Tel aviv, Israel
    Tel Aviv University, Tel Aviv, Israel
  • Emmaneulle Kohn
    Ophthalmology, Tel Aviv Medical Center, Tel aviv, Israel
    Tel Aviv University, Tel Aviv, Israel
  • Meirav Sella
    Plastic and Reconstructive Surgery, Tel Aviv Medical Center, Tel Aviv, Israel
    Tel Aviv University, Tel Aviv, Israel
  • Nir Shani
    Plastic and Reconstructive Surgery, Tel Aviv Medical Center, Tel Aviv, Israel
    Tel Aviv University, Tel Aviv, Israel
  • Benjamin Meilik
    Plastic and Reconstructive Surgery, Tel Aviv Medical Center, Tel Aviv, Israel
    Tel Aviv University, Tel Aviv, Israel
  • Eyal Gur
    Plastic and Reconstructive Surgery, Tel Aviv Medical Center, Tel Aviv, Israel
    Tel Aviv University, Tel Aviv, Israel
  • Anat Loewenstein
    Ophthalmology, Tel Aviv Medical Center, Tel aviv, Israel
    Tel Aviv University, Tel Aviv, Israel
  • adiel barak
    Ophthalmology, Tel Aviv Medical Center, Tel aviv, Israel
    Tel Aviv University, Tel Aviv, Israel
  • Footnotes
    Commercial Relationships Aya Barzelay, None; Ran Levy, None; Emmaneulle Kohn, None; Meirav Sella, None; Nir Shani, None; Benjamin Meilik, None; Eyal Gur, None; Anat Loewenstein, None; adiel barak, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 1826. doi:
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    • Get Citation

      Aya Barzelay, Ran Levy, Emmaneulle Kohn, Meirav Sella, Nir Shani, Benjamin Meilik, Eyal Gur, Anat Loewenstein, adiel barak, ; Therapeutic potential of adipose tissue derived mesenchymal stem cells for AMD - migration, trophic anti-angiogenic effects and differentiation. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):1826.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: Hypoxic stress contributes to RPE dysfunction in AMD. We aimed to examine the paracrine activity and differentiation potential of adipose tissue derived mesenchymal stem cells (ASCs) when exposed to hypoxic and normoxic retinal pigment epithelium (RPE) in vitro.

Methods: In order to mimic AMD environment, RPE cells were subjected to 1% O2 hypoxia. First, migratory capacity of ASCs towards hypoxic RPE conditioned medium was examined by Transwell migration assay. Then, to investigate the paracrine activity of these cells, ASCs were cultured with RPE conditioned medium; Expression of growth factors, chemokine receptors and angiogenic agents were studied by qRT-PCR and immunostaining. Additionally, differentiation capacity to RPE was examined by culturing ASCs with RPE conditioned medium, activin A and nicotinamide. Differentiation markers were assessed with qRT-PCR and immunostaining.

Results: ASCs exhibited enhanced migration towards hypoxic RPE (3.4 folds ±0.37 p<0.0009) when compared to normoxic RPE, by upregulation of CXCR4 (9.5 folds±0.17 p=0.002). ASCs increased expression of the trophic factor BDNF (2.2±0.3 folds p<0.05) and anti angiogenic agent serpinb5 (2.3±1.6 folds p<0.05) when exposed to hypoxic RPE. ASCs demonstrated differentiation potential to RPE by upregulation of early eye field markers (pax6 2.6±0.8, six3 1.4±0.7, rax 1.4±0.2, otx2 2.2±0.7 folds) at 1-2 weeks and RPE markers (rlbp1 3.8±0.7, best1 2.3±0.7, emmprin 2±0.2, zo-1 2.2±0.4, tyrosinase 5.5±0.8, RPE65 3.8±1.6 folds) at 4 weeks.

Conclusions: ASCs migrate towards hypoxic RPE and secrete trophic and anti angiogenic factors. ASCs also exhibit differentiation capacity to RPE. These data may imply to a therapeutic potential of ASCs when exposed to hypoxic RPE.

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