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Vivien Jane Coulson-Thomas, Tarsis Ferreira, Mingxia Sun, Vincent Hascall; The Hyaluronan Rich Limbal Stem Cell Niche regulates Limbal Stem Cell Differentiation. Invest. Ophthalmol. Vis. Sci. 2018;59(9):2988.
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© ARVO (1962-2015); The Authors (2016-present)
Limbal stem cells (LSCs), required for reconstituting the corneal epithelium after injury, are present in the limbal region of the cornea. Injury to the cornea that causes to substantial damage to the LSCs or the LSC niche (LSCN) may lead to LSC deficiency (LSCD), a serious medical condition that can ultimately lead to complete loss of vision. LSC transplantation is a common surgical procedure that is carried out all around the world with an overall success rate of 60%- 70%. A major hurdle in culturing LSCs ex vivo is that they readily differentiate into central corneal epithelial cells (CECs), hampering their use for therapeutic applications. We postulate that charactering the HA matrix within the limbus and understanding how it regulates LSCs could be used to improve ex vivo LSC expansion conditions.
Hyaluronan (HA) is naturally synthesized by hyaluronan synthases (HASs), and vertebrates have the following three types: HAS1, HAS2, and HAS3. Wild-type and HAS and TSG-6 knockout mice - HAS1-/-;HAS3-/-, HAS2Δ/ΔCorEpi, TSG-6-/- - were used to determine the importance of the HA niche in LSC differentiation and specification. The efficacy of HA based matrices for maintaining LSCs and CECs isolated from HAS1-/-;HAS3-/-, HAS2Δ/ΔCorEpi, TSG-6-/- and wild-type mice in vitro were tested.
Our work demonstrates that the LSCN is composed of a hyaluronan (HA) rich matrix which assembles into an intricate HA specific network supporting the LSCs. The composition of the specialized HA matrix in the limbal region differs from that present in the rest of the corneal epithelium. The disruption of the specific HA matrix within the LSCN leads to a loss of LSCs and compromised corneal epithelial regeneration. LSCs seeded on HA-based matrices maintain their stemness during ex vivo expansion. Interestingly, CECs seeded on HA-based matrices also express LSC markers. Our data demonstrates that the use HA based substrates supports the ex vivo expansion of LSCs.
Our findings show HA plays a major role maintaining the LSC phenotype. Culturing LSCs on HA-based surfaces helps to maintain the LSC phenotype throughout ex vivo expansion. Therefore, we postulate that HA plays an important role in regulating the LSC phenotype both in vivo and ex vivo.
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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