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2017 ; 58
(11
): 4407-4421
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Hyaluronan Rich Microenvironment in the Limbal Stem Cell Niche Regulates Limbal
Stem Cell Differentiation
#MMPMID28863216
Gesteira TF
; Sun M
; Coulson-Thomas YM
; Yamaguchi Y
; Yeh LK
; Hascall V
; Coulson-Thomas VJ
Invest Ophthalmol Vis Sci
2017[Sep]; 58
(11
): 4407-4421
PMID28863216
show ga
PURPOSE: Limbal epithelial stem cells (LSCs), located in the basal layer of the
corneal epithelium in the corneal limbus, are vital for maintaining the corneal
epithelium. LSCs have a high capacity of self-renewal with increased potential
for error-free proliferation and poor differentiation. To date, limited research
has focused on unveiling the composition of the limbal stem cell niche, and, more
important, on the role the specific stem cell niche may have in LSC
differentiation and function. Our work investigates the composition of the
extracellular matrix in the LSC niche and how it regulates LSC differentiation
and function. METHODS: 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-/-, HAS2?/?CorEpi,
TSG-6-/--were used to determine the importance of the HA niche in LSC
differentiation and specification. RESULTS: Our data demonstrate that the LSC
niche is composed of a HA rich extracellular matrix. HAS1-/-;HAS3-/-,
HAS2?/?CorEpi, and TSG-6-/- mice have delayed wound healing and increased
inflammation after injury. Interestingly, upon insult the HAS knock-out mice
up-regulate HA throughout the cornea through a compensatory mechanism, and in
turn this alters LSC and epithelial cell specification. CONCLUSIONS: The LSC
niche is composed of a specialized HA matrix that differs from that present in
the rest of the corneal epithelium, and the disruption of this specific HA matrix
within the LSC niche leads to compromised corneal epithelial regeneration.
Finally, our findings suggest that HA has a major role in maintaining the LSC
phenotype.
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