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other·ophthalmology, cornea, preclinical research, ocular immunology, biomedical research·PMC10341195

ABCB5+ Limbal Epithelial Stem Cells Inhibit Developmental but Promote Inflammatory (Lymph) Angiogenesis While Preventing Corneal Inflammation

Cells · 12 authors, 12 centres

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TL;DR

This preclinical study using ABCB5 knockout mice and human cell cultures found that ABCB5-positive limbal epithelial stem cells have a dual, context-dependent role: they inhibit developmental (lymph)angiogenesis but promote inflammatory lymphangiogenesis in adulthood while also exerting anti-inflammatory effects.

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The study investigated the role of ABCB5-positive limbal epithelial stem cells (LESCs) in corneal (lymph)angiogenesis and inflammation using an ABCB5 knockout (KO) mouse model and magnetic-sorted cultured human limbal epithelial cells. In developing mice (4 weeks), ABCB5KO showed increased limbal lymphatic and blood vascular network complexity compared to wild-type. In an adult suture-induced inflammation model, wild-type mice had more lymphatic vessel sprouts than ABCB5KO, suggesting a pro-lymphangiogenic role for ABCB5 under inflammation. In vitro, conditioned media from ABCB5+ human cells stimulated proliferation and migration of human blood and lymphatic endothelial cells. Proteomic analysis revealed ABCB5+ cells have a profile with upregulated pro-(lymph)angiogenic factors and downregulated anti-angiogenic factors like Thrombospondin-1, alongside an anti-inflammatory profile. The study concludes ABCB5+ LESCs have a novel dual function, inhibiting developmental angiogenesis but promoting inflammatory lymphangiogenesis, which is clinically relevant for LESC therapies.

STUDY TYPE

other

SPECIALTY

ophthalmology

SUMMARISED BY

AI pipeline

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ORIGINAL PAPER

PMC10341195

ABCB5+ Limbal Epithelial Stem Cells Inhibit Developmental but Promote Inflammatory (Lymph) Angiogenesis While Preventing Corneal Inflammation

Cells

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ABSTRACT

The limbus, the vascularized junction between the cornea and conjunctiva, is thought to function as a barrier against corneal neovascularization. However, the exact mechanisms regulating this remain unknown. In this study, the limbal epithelial stem cell (LESC) marker ABCB5 was used to investigate the role of LESCs in corneal neovascularization. In an ABCB5KO model, a mild but significant increase of limbal lymphatic and blood vascular network complexity was observed in developing mice (4 weeks) but not in adult mice. Conversely, when using a cornea suture model, the WT animals exhibited a mild but significant increase in the number of lymphatic vessel sprouts compared to the ABCB5KO, suggesting a contextual anti-lymphangiogenic effect of ABCB5 on the limbal vasculature during development, but a pro-lymphangiogenic effect under inflammatory challenge in adulthood. In addition, conditioned media from ABCB5-positive cultured human limbal epithelial cells (ABCB5+) stimulated human blood and lymphatic endothelial cell proliferation and migration. Finally, a proteomic analysis demonstrated ABCB5+ cells have a pro(lymph)angiogenic as well as an anti-inflammatory profile. These data suggest a novel dual, context-dependent role of ABCB5+ LESCs, inhibiting developmental but promoting inflammatory (lymph)angiogenesis in adulthood and exerting anti-inflammatory effects. These findings are of high clinical relevance in relation to LESC therapy against blindness.

CITATION EXPORT

Berbang Meshko, Thomas L. A. Volatier, Karina Hadrian et al.. ABCB5+ Limbal Epithelial Stem Cells Inhibit Developmental but Promote Inflammatory (Lymph) Angiogenesis While Preventing Corneal Inflammation. Cells. (2023). https://doi.org/10.3390/cells12131731

AUTHORS

12 · 12 CENTRES

Berbang Meshko, Thomas L. A. Volatier, Karina Hadrian, Shuya Deng, Yanhong Hou, Mark Andreas Kluth, Christoph Ganss, Markus H. Frank, Natasha Y. Frank, Bruce Ksander, Claus Cursiefen, Maria Notara

1Department of Ophthalmology, University of Cologne, 50937 Cologne, Germany; [email protected] (B.M.); [email protected] (T.L.A.V.); [email protected] (Y.H.);
2TICEBA GmbH, Im Neuenheimer Feld 517, 69120 Heidelberg, Germany; [email protected] (M.A.K.); [email protected] (C.G.)
3RHEACELL GmbH & Co. KG, Im Neuenheimer Feld 517, 69120 Heidelberg, Germany
4Transplant Research Program, Boston Children’s Hospital, Boston, MA 02115, USA
5Harvard Skin Disease Research Center, Department of Dermatology, Brigham and Women’s Hospital, Boston, MA 02115, USA
6Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA; [email protected]
7School of Medical and Health Sciences, Edith Cowan University, Perth, WA 6027, Australia
8Department of Medicine, VA Boston Healthcare System, Boston, MA 02132, USA
9Division of Genetics, Brigham and Women’s Hospital, Boston, MA 02115, USA
10Massachusetts Eye & Ear Infirmary, Schepens Eye Research Institute, Boston, MA 02114, USA; [email protected]
11Center for Molecular Medicine Cologne (CMMC), University of Cologne, 50937 Cologne, Germany
12Institute for Genome Stability in Ageing and Disease, CECAD Research Center, Joseph-Stelzmann-Str. 26, 50931 Cologne, Germany

EDITOR / REVIEWER

Volker Enzmann