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Enzhi Yang, AJAY KUMAR, Yiqin Du; Possible Autologous Stem Cell Resources for Trabecular Meshwork Regeneration. Invest. Ophthalmol. Vis. Sci. 2018;59(9):4733.
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© ARVO (1962-2015); The Authors (2016-present)
Using stem cells to repopulate and regenerate the trabecular meshwork (TM) could restore the aqueous humor outflow pathway and reduce intraocular pressure (IOP) for glaucoma treatment. This study aims to explore the possibility of autologous stem cell resources, such as adipose-derive stem cells (ADSCs) and corneal stromal stem cells (CSSCs) for TM regeneration.
Human ADSCs were obtained from the Adipose Stem Center at University of Pittsburgh. CSSCs were isolated from human corneal limbus which is accessible by biopsy for autologous purpose. The cell stemness was assessed by colony forming efficiency (CFE), stem cell marker OCT4 expression and multipotency. Stem cells were induced for TM cell differentiation in TM cell-conditioned medium on TM cell extracellular matrix. The induced cells were examined by immunostaining and qPCR for TM cell marker CHI3L1 and AQP1 expression. The cells were also treated with dexamethasone to detect MYOC expression and Cross-Linked Actin Networks (CLANs) formation. The undifferentiated and differentiated cells were injected into wildtype mouse anterior chamber. IOP was measured regularly using a rebound tonometer and injected cells were detected by immunofluorescent staining on wholemounts and cryosections.
Both human ADSCs and CSSCs were clonogenic, expressed stem cell marker OCT4. They were multipotent with osteogenesis, adipogenesis and neuronalgenesis. After TM cell induction, ADSCs and CSSCs expressed CHI3L1 and AQP1 on both RNA and protein levels. With dexamethasone treatment for 11 days, MYOC expression increased and cell actins reorganized forming CLANs, similar to primary TM cells. Both undifferentiated and differentiated cells were able to home to the TM region in vivo, maintaining normal IOP in normal mice at various time points post injection. The homed cells were viable and integrated into the cell layers of the original TM structure.
Both ADSCs and TMSCs were able to differentiate into TM cells in vitro and to home to the TM region in vivo for TM regeneration. The differences between ADSCs and TMSCs were not significant for TM cell differentiation and homing to the TM. Further studies are needed to investigate long-term effects on restoring TM function in glaucomatous animal models. This may open a door for autologous stem cell-based therapy for glaucoma.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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