Corneal blindness is the fourth leading cause of blindness in the world. Limbal stem cell deficiency (LSCD) is a blinding eye disorder due to the dysfunction or absence of corneal epithelial stem cells or limbal stem cells (LSCs), which maintain the normal homeostasis of the transparent corneal epithelium. LSCD, which is often undiagnosed and most challenging to treat is seen in many common eye diseases. The most desired treatment is transplantation of autologous LSCs in severe/total unilateral LSCD. The efficacy of transplantation of cultivated LSCs (cLSCs) has been reported in more than 37 studies since 1997. However, the cultivation protocol and the clinical outcome measures vary from study to study. Only three studies used GMP-compliant cLSCs. In addition, the success rate has not improved over the last two decades. To improve the efficacy and safety profile of the cLSCs, clinical trials using a standardized LSC cultivation and clinical protocol are necessary. To accomplish this goal, our laboratory has established a xenobiotic-free and feeder-free LSC culture method that can consistently produce cLSCs with properties that meet the criteria for high-level clinical success. Quantifiable in vitro parameters have been developed to characterize cLSCs and a newly developed in vivo imaging technique can be used to quantify LSC function in patients. In this proposal, we will establish these quantifiable in vitro parameters as in-process quality controls for the production of cLSCs and establish in vivo parameters as clinical outcome measures to objectively assess clinical outcomes. A pilot clinical study to evaluate the safety and efficacy of cLSCs produced under GMP condition will be conducted. Implementation of these in vitro and in vivo quantifiable parameters will make it possible to establish a standardized patient- specific stem cell therapy. The knowledge learned from the proposed study will form the foundation for the development of the next generation patient-specific limbal stem cell therapy.

Public Health Relevance

Limbal stem cell deficiency (LSCD) is a blinding eye disorder due to the deficiency of functional corneal epithelial stem cells or limbal stem cells (LSCs), which maintain the normal homeostasis of the transparent corneal epithelium. The proposed studies aim to establish a standardized LSC cultivation protocol and a novel in vivo imaging technique to quantify LSC function in patients. A pilot clinical study will be conducted to investigate the safety and feasibility of a standardized protocol to treat LSCD.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
2R01EY021797-06A1
Application #
9662575
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Mckie, George Ann
Project Start
2012-09-01
Project End
2024-01-31
Budget Start
2019-02-01
Budget End
2020-01-31
Support Year
6
Fiscal Year
2019
Total Cost
Indirect Cost
Name
University of California Los Angeles
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
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Le, Qihua; Samson, C Michael; Deng, Sophie X (2018) A Case of Corneal Neovascularization Misdiagnosed as Total Limbal Stem Cell Deficiency. Cornea 37:1067-1070
Aravena, Carolina; Yu, Fei; Deng, Sophie X (2017) Outcomes of Descemet Membrane Endothelial Keratoplasty in Patients With Previous Glaucoma Surgery. Cornea 36:284-289
González, Sheyla; Chen, Luxia; Deng, Sophie X (2017) Comparative Study of Xenobiotic-Free Media for the Cultivation of Human Limbal Epithelial Stem/Progenitor Cells. Tissue Eng Part C Methods 23:219-227
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Le, Qihua; Yang, Yujing; Deng, Sophie X et al. (2017) Correlation between the existence of the palisades of Vogt and limbal epithelial thickness in limbal stem cell deficiency. Clin Exp Ophthalmol 45:224-231
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González, Sheyla; Mei, Hua; Nakatsu, Martin N et al. (2016) A 3D culture system enhances the ability of human bone marrow stromal cells to support the growth of limbal stem/progenitor cells. Stem Cell Res 16:358-64

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