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Benjamin Bakondi, YuChun Tsai, Bin Lu, Sergey Girman, Lin Shen, Melissa Kaye Jones, Shaomei Wang; Is Mesenchymal Stem Cell Homing To The Injured Retina Required For Visual Preservation In The RCS Rat?. Invest. Ophthalmol. Vis. Sci. 2014;55(13):1377. doi: https://doi.org/.
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Retinal degeneration is slowed by intravenous (IV) injection of allogeneic bone marrow-derived mesenchymal stem cells (MSCs) prior to the onset of degeneration in the RCS rat. However, the mechanism(s) for MSC-mediated retinal protection has yet been determined. It is unclear whether MSC homing to the retina is required for vision rescue and is the subject of the current investigation.
The predominant mechanism for MSC migration to tissue injury is mediated through the CXCR4 chemokine receptor, which was stimulated (SDF-1; 50ng/ml) or antagonized (AMD3100; 10uM) for 30 minutes prior to infusion of allogeneic MSCs (1.6 x 106 cells) into RCS rats on postnatal day 25. Optokinetic responses (OKR) and electroretinograms (ERG) were performed on postnatal day 60. For cell tracking experiments, MSCs were labeled with a lipophilic fluorescent dye (PKH26 or PKH67; Sigma) prior to injection and cell distribution was determined 24 and 72 hours post-injection via flow cytometry and histological examination.
SDF-1 pre-treatment enhanced the migration capacity of MSCs in vitro, while AMD3100 pre-treatment reduced it, compared with control (saline) treatment. OKR and ERG recordings showed that injection of SDF-1 pre-treated MSCs preserved visual function in RCS rats compared with injection of saline or AMD3100-treated MSCs. Fluorescent donor cells were not detected at or near the injury site at 24 or 72 hours, the typical timeframe for MSC chemotaxis. MSCs were detected in the blood circulation, lungs, and bone marrow.
SDF-1 pre-treatment of MSCs enhanced the preservation of vision in the RCS rat. Further study is under way to determine whether MSC homing to the retina is required for visual preservation.
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