Lymphangiogenesis May Play a Role in Cultivated Limbal Stem Cell Transplant Rejection

Zakaria, Nadia; Koppen, Carina; Berneman, Zwi N.; Tassignon, Marie-José

doi:10.3109/09273948.2012.708958

Cited by 3 publications

(5 citation statements)

References 15 publications

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“…New therapies target both lymphatic and blood vessel formation in the cornea as they also contribute to corneal graft and limbal stem cell graft rejection and sensitization in prevascularized corneas [ 93 ]. Corneal lymphangiogenesis is mainly regulated by VEGF-C which promotes growth of both lymphatic and blood vessels.…”

Section: Angiogenic Privilege and Regulation Of Pro- And Antiangiomentioning

confidence: 99%

The Role of Limbal Epithelial Stem Cells in Regulating Corneal (Lymph)angiogenic Privilege and the Micromilieu of the Limbal Niche following UV Exposure

Notara

Lentzsch

Coroneo

et al. 2018

Stem Cells International

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The cornea is a clear structure, void of blood, and lymphatic vessels, functioning as our window to the world. Limbal epithelial stem cells, occupying the area between avascular cornea and vascularized conjunctiva, have been implicated in tissue border maintenance, preventing conjunctivalisation and propagation of blood and lymphatic vessels into the cornea. Defects in limbal epithelial stem cells are linked to corneal neovascularisation, including lymphangiogenesis, chronic inflammation, conjunctivalisation, epithelial abnormalities including the presence of goblet cells, breaks in Bowman's membrane, persistent epithelial defects and ulceration, ocular surface squamous neoplasia, lipid keratopathy, pain, discomfort, and compromised vision. It has been postulated that pterygium is an example of focal limbal deficiency. Previous reports showing changes occurring in limbal epithelium during pterygium pathogenesis suggest that there is a link to stem cell damage. In this light, pterygium can serve as a model disease of UV-induced stem cell damage also characterised by corneal blood and lymphangiogenesis. This review focuses on the role of corneal and limbal epithelial cells and the stem cell niche in maintaining corneal avascularity and corneal immune privilege and how this may be deregulated following UV exposure. We present an overview of the PUBMED literature in the field as well as recent work from our laboratories.

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Section: Angiogenic Privilege and Regulation Of Pro- And Antiangiomentioning

confidence: 99%

The Role of Limbal Epithelial Stem Cells in Regulating Corneal (Lymph)angiogenic Privilege and the Micromilieu of the Limbal Niche following UV Exposure

Notara

Lentzsch

Coroneo

et al. 2018

Stem Cells International

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“…Unfortunately, immune rejection still occurred, and this pioneering attempt failed (88). Lymphangiogenesis was observed in the removed graft, which again emphasizes the importance of IAL in transplantation (88). Another important consideration is the ideal timing of transplantation if inflammation has already occurred.…”

Section: Transplantation and Rejectionmentioning

confidence: 99%

“…87) in a patient with a history of two failed penetrating keratoplasties (88). Unfortunately, immune rejection still occurred, and this pioneering attempt failed (88). Lymphangiogenesis was observed in the removed graft, which again emphasizes the importance of IAL in transplantation (88).…”

Section: Transplantation and Rejectionmentioning

confidence: 99%

“…A case report describes an allogeneic and autologous cultivated limbal stem cell graft transplantation instead of a conventional keratolimbal allograft (because the antigenicity of the graft is thought to decrease during culture, causing lower rates of rejection; ref. 87) in a patient with a history of two failed penetrating keratoplasties (88). Unfortunately, immune rejection still occurred, and this pioneering attempt failed (88).…”

Section: Transplantation and Rejectionmentioning

confidence: 99%

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Inflammation-associated lymphangiogenesis: a double-edged sword?

Kim¹,

Kataru²,

Koh³

2014

J. Clin. Invest.

195

146

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Lymphangiogenesis and lymphatic vessel remodeling are complex biological processes frequently observed during inflammation. Accumulating evidence indicates that inflammation-associated lymphangiogenesis (IAL) is not merely an endpoint event, but actually a phenomenon actively involved in the pathophysiology of various inflammatory disorders. The VEGF-C/VEGFR-3 and VEGF-A/VEGF-R2 signaling pathways are two of the best-studied pathways in IAL. Methods targeting these molecules, such as prolymphangiogenic or antilymphatic treatments, were found to be beneficial in various preclinical and/or clinical studies. This Review focuses on the most recent achievements in the fields of lymphatic biology relevant to inflammatory conditions. Additionally, preclinical and clinical therapies that modulate IAL are summarized.

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“…Quantification of corneal neovascularization after transplantation has also been described as a means of assessing post-transplantation success in cases of autologous cultured LSC transplantation, attesting to the importance of this phenomenon in maintaining transplanted limbal graft viability [ 117 ]. Zakaria et al [ 118 ] reported a specific function of lymphangiogenesis in cultured LSC transplantation rejection, highlighting the role of lymphatics as the afferent arm of immune rejection and the role of blood vessels as the efferent arm of immune rejection. It is possible that adjuvant treatment targeting neovascularization may improve transplantation outcomes in LSCD.…”

Section: Future Directions: Modulation Of Non-limbal and Limbal Stem ...mentioning

confidence: 99%

Therapeutic Strategies for Restoring Perturbed Corneal Epithelial Homeostasis in Limbal Stem Cell Deficiency: Current Trends and Future Directions

Masood

Chang

Akbar

et al. 2022

Cells

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Limbal stem cells constitute an important cell population required for regeneration of the corneal epithelium. If insults to limbal stem cells or their niche are sufficiently severe, a disease known as limbal stem cell deficiency occurs. In the absence of functioning limbal stem cells, vision-compromising conjunctivalization of the corneal epithelium occurs, leading to opacification, inflammation, neovascularization, and chronic scarring. Limbal stem cell transplantation is the standard treatment for unilateral cases of limbal stem cell deficiency, but bilateral cases require allogeneic transplantation. Herein we review the current therapeutic utilization of limbal stem cells. We also describe several limbal stem cell markers that impact their phenotype and function and discuss the possibility of modulating limbal stem cells and other sources of stem cells to facilitate the development of novel therapeutic interventions. We finally consider several hurdles for widespread adoption of these proposed methodologies and discuss how they can be overcome to realize vision-restoring interventions.

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Lymphangiogenesis May Play a Role in Cultivated Limbal Stem Cell Transplant Rejection

Cited by 3 publications

References 15 publications

The Role of Limbal Epithelial Stem Cells in Regulating Corneal (Lymph)angiogenic Privilege and the Micromilieu of the Limbal Niche following UV Exposure

The Role of Limbal Epithelial Stem Cells in Regulating Corneal (Lymph)angiogenic Privilege and the Micromilieu of the Limbal Niche following UV Exposure

Inflammation-associated lymphangiogenesis: a double-edged sword?

Therapeutic Strategies for Restoring Perturbed Corneal Epithelial Homeostasis in Limbal Stem Cell Deficiency: Current Trends and Future Directions

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