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Yiqin Du, Hongmin Yun, Enzhi Yang, Joel Schuman; Stem Cells from Trabecular Meshwork Home to Damaged TM Tissue in vivo. Invest. Ophthalmol. Vis. Sci. 2013;54(15):3555.
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We recently described a population of multipotent stem cells present in human trabecular meshwork (TM) tissue which can differentiate to functional TM cells in vitro and in vivo (Du et al, IOVS 2012; 53:1566). This study explored the hypothesis that these human trabecular meshwork stem cells (TMSCs) when introduced into the eye can home to damaged trabecular meshwork (TM) and will repair the tissue damage.
Human TMSCs were isolated and passaged as previously reported. Damage was produced in a 180° arc of the TM of adult C57BL/6 mice by laser photocoagulation using a 532nm green laser. After laser damage, 50,000 of either TMSCs or fibroblasts from human corneal stroma were injected into mouse anterior chamber. Cells were prelabeled with DiO before injection. Intraocular pressure (IOP) was measured regularly for 2 weeks after cell injection. DiO labeled cells were detected by confocal microscope on tissue wholemounts and cryosections. Expression of stem cell marker MUC1 or differentiated TM cell marker CHI3L1 was examined by immunostaining on wholemount or cryosections. Transmission electron microscopy was used to compare the TM with TMSC- and fibroblast-transplantation.
Injection of human TMSCs did not increase recipient mouse IOP. Injected TMSCs localized specifically to the damaged TM region but not the unwounded TM or other normal tissues. In contrast, injected fibroblasts were detected in the TM, cornea and iris. Some injected TMSCs maintained expression of MUC1, whereas some differentiated into TM cells with expression of CHI3L1. TM tissue damage by laser photocoagulation was repaired by injected TMSCs. The damage to the TM was not recovered in mice with fibroblasts transplantation.
Human TMSCs have the ability to home to damaged TM tissue and adopt a TM phenotype, with the possibility of repairing damaged TM tissue. This opens a door for stem cell-based therapy for glaucoma.
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