ESCRS - Cultivating Progress for LSCD ;
ESCRS - Cultivating Progress for LSCD ;
Cornea, Corneal Therapeutics

Cultivating Progress for LSCD

Clinical trials now underway could further support promise shown by cultivated limbal stem cells.

Cultivating Progress for LSCD
Cheryl Guttman Krader
Cheryl Guttman Krader
Published: Monday, April 1, 2024

Research advances are reshaping the diagnosis and treatment of limbal stem cell deficiency (LSCD), according to Sophie X Deng MD, PhD.

Stage classification is part of the foundation for management decisions, so in diagnosis, Dr Deng said recent evidence indicates biomarkers of LSC function identified by in vivo confocal microscopy may provide more accurate information for staging than clinical examination.

She illustrated her point by presenting a case of a patient misdiagnosed with stage III LSCD based on clinical exam but found to have minimal LSCD when assessed with confocal microscopy. Dr Deng also noted using the in vivo imaging tool revealed hidden normal epithelial cells in eyes staged with total LSCD by clinical exam.

“These existing limbal epithelial cells can be retrieved by targeted biopsy and expanded in culture to achieve autologous stem cell transplantation that is favoured over the use of allogeneic cells whenever possible,” she said.

“Although both simple limbal epithelial transplantation (SLET) and cultivated limbal epithelial transplantation (CLET) can provide excellent results, cultivated LSCs might be the preferred choice for treating total LSCD, while SLET might be sufficient in eyes with less severe LSCD. Randomised controlled clinical trials using a set of standardised disease staging criteria are necessary to compare the efficacy of different therapies.”

New methods for rejuvenation

Cases of stage I LSCD require observation and optimisation of the ocular surface and might provide enough improvement of the corneal surface to avoid limbal stem cell transplantation in eyes with moderate LSCD—although Dr Deng noted promising results obtained in ongoing research indicate the possibility of treating the latter eyes with mesenchymal stem cells or growth factors that will promote the growth of residual LSCs in the future.

“It has been shown that mesenchymal stem cells and their secretome have anti-scarring properties and can promote epithelial wound healing,” she said. “Perhaps in the future, topical medications made from the extracellular vesicles/secretome of the mesenchymal stem cells might replace or reduce the need for corneal transplantation to treat corneal scarring and epithelial defects.”

Progress in LSC cultivation

CLET is not available in the United States because the cultivation process involves xenogeneic murine feeder cells and foetal bovine serum, making it more challenging to meet the FDA regulatory requirement. Research in the field of LSC transplantation also includes efforts to improve the safety of manufacturing LSCs by removing all animal products.

Dr Deng identified Dr Ula Jurkunas and colleagues as one of the teams in the US actively working on this area and cited their development of a xenobiotic- and feeder-free LSC manufacturing process that would meet FDA requirements. Dr Deng and colleagues have also been working on a new process for manufacturing LSCs and have been successful in devising a robust method with a favourable safety profile.

Recruitment is now underway for patients with severe to total LSCD for participation in a phase 1 study she is conducting investigating the safety and feasibility of expanding cultivated autologous LSCs using their manufacturing process. The preliminary data show promising safety and efficacy results. Dr Deng provided the clinicaltrials.gov ID number (NCT03957954) and asked colleagues to refer potential candidates.

Dr Deng spoke at AAO 2023 in San Francisco, US.

Sophie X Deng MD, PhD is Professor of Ophthalmology and Co-Chief Cornea Division, Stein Eye Institute, UCLA, Los Angeles, California, US. deng@jsei.ucla.edu

 

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