Modulation of Retinal Wound Healing by Systemically Administered Bone Marrow-Derived Mesenchymal Stem Cells

Purpose: To evaluate whether systemically injected bone marrow-derived mesenchymal stem cells (MSCs) can be incorporated into neuroretinal tissues and play an important role in retinal wound healing in the laser-induced retinal trauma model. Methods: Retinotomies were made by applying an Nd:YAG laser to rat retina. On the first day after the injuries, cell suspensions that were obtained from the same line of rat (containing 1 × 106 green fluorescence protein [GFP]-marked bone marrow-derived MSCs) were injected through a tail vein in the experimental group and phosphate buffer solution (PBS) was injected in the same way in the control group. Fundus photographs were taken serially for fundus examination and eyeballs were enucleated for histological studies that were conducted at five and seven weeks after MSC and PBS injection. After the tissues were prepared, the retinotomy sites were observed with routine histological staining and confocal microscopy. Results: Retinal detachment resolved in the experimental group, whereas it progressed in the control group. The retinotomy sites closed partially with identifiable GFP positive cells 5 weeks after MSC injection. At 7 weeks after MSC injection, complete healing without retinal detachment and plentiful GFP positive cells were observed at the transitional zone between damaged and normal retina. Conclusions: Systemically administered GFP-marked MSCs may be incorporated into the neuroretinal tissues and play an important role in the wound modulation of physically damaged retinal tissues.