Multipotent stem cells from trabecular meshwork become phagocytic TM cells

Yiqin Du, Danny S. Roh, Mary M. Mann, Martha L. Funderburgh, James L. Funderburgh, Joel S. Schuman

    Research output: Contribution to journalArticle

    Abstract

    PURPOSE. To isolate and characterize stem cells from human trabecular meshwork (TM) and to investigate the potential of these stem cells to differentiate into TM cells. METHODS. Human trabecular meshwork stem cells (TMSCs) were isolated as side population cells by fluorescence-activated cell sorting or isolated by clonal cultures. Passaged TMSCs were compared with primary TM cells by immunostaining and quantitative RT-PCR. TMSC purity was assessed by flow cytometry and TMSC multipotency was examined by induction of neural cells, adipocytes, keratocytes, or TM cells. Differential gene expression was detected by quantitative RT-PCR, immunostaining, and immunoblotting. TM cell function was evaluated by phagocytic assay using inactivated Staphylococcus aureus bioparticles. RESULTS. Side population and clonal isolated cells expressed stem cell markers ABCG2, Notch1, OCT-3/4, AnkG, and MUC1 but not TM markers AQP1, MGP, CHI3L1, or TIMP3. Passaged TMSCs are a homogeneous population with >95% cells positive to CD73, CD90, CD166, or Bmi1. TMSCs exhibited multipotent ability of differentiation into a variety of cell types with expression of neural markers neurofilament, β-tubulin III, GFAP; or keratocyte-specific markers keratan sulfate and keratocan; or adipocyte markers ap2 and leptin. TMSC readily differentiated into TM cells with phagocytic function and expression of TM markers AQP1, CHI3L1, and TIMP3. CONCLUSIONS. TMSCs, isolated as side population or as clones, express specific stem cell markers, are homogeneous and multipotent, with the ability to differentiate into phagocytic TM cells. These cells offer a potential for development of a novel stem cell-based therapy for glaucoma.

    Original languageEnglish (US)
    Pages (from-to)1566-1575
    Number of pages10
    JournalInvestigative Ophthalmology and Visual Science
    Volume53
    Issue number3
    DOIs
    StatePublished - Mar 1 2012

    ASJC Scopus subject areas

    • Ophthalmology
    • Sensory Systems
    • Cellular and Molecular Neuroscience

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    Du, Y., Roh, D. S., Mann, M. M., Funderburgh, M. L., Funderburgh, J. L., & Schuman, J. S. (2012). Multipotent stem cells from trabecular meshwork become phagocytic TM cells. Investigative Ophthalmology and Visual Science, 53(3), 1566-1575. https://doi.org/10.1167/iovs.11-9134