Purchase this article with an account.
Yiqin Du, Mary M. Mann, Martha L. Funderburgh, James L. Funderburgh, Joel S. Schuman; Multipotent Stem Cells from Trabecular Meshwork Home to TM. Invest. Ophthalmol. Vis. Sci. 2011;52(14):6617.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
This study tested the hypotheses that stem cells from human trabecular meshwork (TMSCs) are an homogeneous population of adult stem cells which can differentiate into multiple cell linages and in the anterior chamber TMSC home to the TM region and differentiate to TM.
TSMC were cultured under conditions which induce differentiation to keratocyte, neural, and adipose cell types. Expression of stem cell and differentiation markers in TMSCs was analyzed by flow cytometry, qPCR, and immunostaining. TMSCs and corneal fibroblasts, prelabeled with DiO, were injected into mouse anterior chamber for 1 and 4 weeks. Wholemount staining of anterior segment detected TM markers AQP1, CHI3L1 and stem cell marker Muc1.
Flow cytometry showed >90% of TMSCs express CD73, CD90, CD166 and Bmi1. On differentiation to TM, expression of stem cell markers ABCG2, CD73, CD90, CD166, Bmi1, Notch1, KLF4 was reduced and expression of TM differentiation markers AQP1, MGP and CHI3L1 was increased statistically significant analyzed by t-test. When cultured as pellets, TMSC secreted keratocyte-specific matrix components keratocan and keratan sulfate. In neural induction condition, TMSCs expressed neurofilament, β-tubulin III and GFAP but lost Muc1 expression. In adipogenic differentiation condition, TMSCs stained positive to oil red O. None of these was observed with TMSCs without induction. In vivo, injected, labeled TMSCs were found localized to the TM region at 1 week. After 4 weeks, the number of labeled cells increased in the TM. Most labeled cells were positive to Muc1 and a few expressed AQP1 and CHI3L1. Injected fibroblasts were also observed in the TM region but expressed neither Muc1 nor AQP1, CHI3L1.
TMSCs are an homogeneous population of multipotent adult stem cells. They can be induced to differentiate into TM cells with decreased expression of stem cell markers and increased expression of TM markers. TMSCs also can be induced to differentiate into corneal keratocytes, neural cells and adipocytes. When the TMSCs were introduced into normal mouse anterior chamber, they home to TM region and some of them differentiated to TM cells while the majority remained stem cells.
This PDF is available to Subscribers Only