Melanocytes as emerging key players in niche regulation of limbal epithelial stem cells

• DOI: 10.1016/j.jtos.2021.08.006
• Publication Date: 2021-08-20T15:52:05Z
• Authors: Naresh Polisetti; Andreas Gießl; Matthias Zenkel; Lukas Heger; Diana Dudziak; Elisabeth Naschbe...; Lena Stich; Alexander Steinka...; Friedrich E. Kruse; Ursula Schlötzer-...
• Keywords: Matrigel; CD80

Limbal melanocytes (LMel) represent essential components of the corneal epithelial stem cell niche and are known to protect limbal stem/progenitor cells (LEPCs) from UV damage by transfer melanosomes. Here, we explored additional functional roles for LMel in homeostasis, immune regulation angiostasis. Human corneoscleral tissues were morphologically analyzed normal, inflammatory wound healing conditions. The effects on LEPCs direct indirect co-culture models using electron microscopy, immunocytochemistry, qRT-PCR, Western blotting assays; mesenchymal stromal murine embryonic 3T3 fibroblasts served as controls. immunophenotype was assessed flow cytometry before after interferon-γ stimulation, their immunomodulatory properties mixed lymphocytes reaction, monocyte adhesion assays cytometric bead arrays. Their angiostatic human umbilical cord endothelial (HUVECs) evaluated proliferation, migration, tube formation assays. formed structural units situ, which could be functionally replicated, including melanosome transfer, co-cultivation vitro. supported during clonal expansion stimulating proliferation suppressed differentiation through contact paracrine effects. Under conditions, increased numbers upregulated expression ICAM-1 MHC II molecules (HLA-DR), but lacked HLA-G, -DP, -DQ costimulatory CD80 CD86. They also found potent suppressors alloreactive T- cytokine secretion, largely depended cell-cell interaction. Moreover, secretome exerted activity inhibiting vascular capillary network formation. These findings suggest that not only professional melanin-producing cells, exert various non-canonical functions homeostasis regulating LEPC maintenance, responses, regulatory, anti-angiogenic may have important implications future regenerative therapies.