Regeneration of a Normal Corneal Surface by Limbal Stem Cell Therapy
Grant Award Details
Grant Type:
Grant Number:
CLIN1-08686
Investigator(s):
Disease Focus:
Human Stem Cell Use:
Award Value:
$4,244,211
Status:
Closed
Progress Reports
Reporting Period:
Final Operational Milestone #4
Grant Application Details
Application Title:
Regeneration of a Normal Corneal Surface by Limbal Stem Cell Therapy
Public Abstract:
Therapeutic Candidate or Device
cultivated patient-specific corneal epithelial stem cells (limblal stem cells, LSC)
Indication
Corneal blindness from inability to heal due to corneal epithelial stem cell deficiency as a results of injury
Therapeutic Mechanism
Limbal stem cell deficiency (LSCD) leads to inability to heal. The most desired treatment is to replace the necessary amount of the stem cell to maintain a normal, transparent corneal surface. Any remaining LSCs will be identified and biopsy from the patient to be expanded in culture. Once sufficient amount of LSCs are produced, these LSCs will then transplanted back to patient's eye to restore a normal corneal surface.
Unmet Medical Need
Cultivated LSCs has been shown to be effective and a safer treatment than direct transplantation for LSCD since 1997 in Europe. This stem therapy is not available in the United States. Our therapy will be the first patient-specific stem cell therapy to treat both unilateral and bilateral LSCD.
Project Objective
IND filling and ready for phase 1 trial
Major Proposed Activities
cultivated patient-specific corneal epithelial stem cells (limblal stem cells, LSC)
Indication
Corneal blindness from inability to heal due to corneal epithelial stem cell deficiency as a results of injury
Therapeutic Mechanism
Limbal stem cell deficiency (LSCD) leads to inability to heal. The most desired treatment is to replace the necessary amount of the stem cell to maintain a normal, transparent corneal surface. Any remaining LSCs will be identified and biopsy from the patient to be expanded in culture. Once sufficient amount of LSCs are produced, these LSCs will then transplanted back to patient's eye to restore a normal corneal surface.
Unmet Medical Need
Cultivated LSCs has been shown to be effective and a safer treatment than direct transplantation for LSCD since 1997 in Europe. This stem therapy is not available in the United States. Our therapy will be the first patient-specific stem cell therapy to treat both unilateral and bilateral LSCD.
Project Objective
IND filling and ready for phase 1 trial
Major Proposed Activities
- LSC manufacture development and certification
- Establishment of manufacture process in GMP facility
- biomarker development
Statement of Benefit to California:
California is the most populated state in the USA. The number of residents with LSCD may disproportionately increase as a result of multiple environmental risk factors. A safe treatment to restore vision would be an important benefit to the people of California.
Our project will further benefit California through the training of new stem-cell researchers, create more jobs, and attract funding from the federal government and investment from the private sector.
Publications
- Stem Cell Res (2016): A 3D culture system enhances the ability of human bone marrow stromal cells to support the growth of limbal stem/progenitor cells. (PubMed: 26896856)
- Ocul Surf (2019): The application of human amniotic membrane in the surgical management of limbal stem cell deficiency. (PubMed: 30633967)
- Ocul Surf (2022): Biomarkers of in vivo limbal stem cell function. (PubMed: 34902592)
- Biofabrication (2021): Bioprinting of dual ECM scaffolds encapsulating limbal stem/progenitor cells in active and quiescent statuses. (PubMed: 34330126)
- Cornea (2018): A Case of Corneal Neovascularization Misdiagnosed as Total Limbal Stem Cell Deficiency. (PubMed: 29781927)
- Cornea (2022): Cell Morphology as an In Vivo Parameter for the Diagnosis of Limbal Stem Cell Deficiency. (PubMed: 34935665)
- Cornea (2017): Characterization of the Corneal Subbasal Nerve Plexus in Limbal Stem Cell Deficiency. (PubMed: 27941384)
- Cornea (2019): Classification of Limbal Stem Cell Deficiency Using Clinical and Confocal Grading. (PubMed: 30371569)
- Cont Lens Anterior Eye (2021): Clinical outcomes and complications of fluid-filled scleral lens devices for the management of limbal stem cell deficiency. (PubMed: 34728142)
- Am J Ophthalmol (2020): Corneal Epithelial Thickness Measured Using Anterior Segment Optical Coherence Tomography as a Diagnostic Parameter for Limbal Stem Cell Deficiency. (PubMed: 32283095)
- Clin Exp Ophthalmol (2017): Correlation between the existence of the palisades of Vogt and limbal epithelial thickness in limbal stem cell deficiency. (PubMed: 27591548)
- Cornea (2022): Cytokeratin 13 Is a New Biomarker for the Diagnosis of Limbal Stem Cell Deficiency. (PubMed: 34743102)
- Ocul Surf (2018): The diagnosis of limbal stem cell deficiency. (PubMed: 29113917)
- Surv Ophthalmol (2019): Diagnostic criteria for limbal stem cell deficiency before surgical intervention-A systematic literature review and analysis. (PubMed: 31276736)
- Am J Ophthalmol (2015): Epithelial Thinning in Limbal Stem Cell Deficiency. (PubMed: 26163009)
- Cornea (2016): Existence of Normal Limbal Epithelium in Eyes With Clinical Signs of Total Limbal Stem Cell Deficiency. (PubMed: 27362882)
- Curr Opin Ophthalmol (2023): Future regenerative therapies for corneal disease. (PubMed: 36602407)
- Cornea (2020): Global Consensus on the Management of Limbal Stem Cell Deficiency. (PubMed: 32639314)
- Prog Retin Eye Res (2021): Human limbal epithelial stem cell regulation, bioengineering and function. (PubMed: 33676006)
- Front Med (Lausanne) (2023): Latent diffusion augmentation enhances deep learning analysis of neuro-morphology in limbal stem cell deficiency. (PubMed: 37908848)
- Am J Ophthalmol (2015): Limbal Basal Cell Density Decreases in Limbal Stem Cell Deficiency. (PubMed: 26149968)
- Cornea (2020): Limbal Stem Cell Deficiency After Glaucoma Surgery. (PubMed: 31977730)
- Exp Eye Res (2021): Limbal stem cell diseases. (PubMed: 33571530)
- Stem Cells Transl Med (2019): Mesenchymal Stem Cells Reduce Corneal Fibrosis and Inflammation via Extracellular Vesicle-Mediated Delivery of miRNA. (PubMed: 31290598)
- Sci Rep (2019): Notch Inhibition Prevents Differentiation of Human Limbal Stem/Progenitor Cells in vitro. (PubMed: 31316119)
- Stem Cells Transl Med (2023): Ocular Surface Regeneration by Limbal Stem Cells Therapies: State of the Art, Challenges, and Perspectives. (PubMed: 37715946)
- JAMA Ophthalmol (2020): Outcomes of Limbal Stem Cell Transplant: A Meta-analysis. (PubMed: 32324211)
- Int J Mol Sci (2021): Regulation of Limbal Epithelial Stem Cells: Importance of the Niche. (PubMed: 34769405)
- Exp Eye Res (2023): Single mRNA detection of Wnt signaling pathway in the human limbus. (PubMed: 36702232)
- AAPS J (2022): Stability and Function of Extracellular Vesicles Derived from Immortalized Human Corneal Stromal Stem Cells: A Proof of Concept Study. (PubMed: 36471035)
- Transl Vis Sci Technol (2018): In Vivo Evaluation of the Limbus Using Anterior Segment Optical Coherence Tomography. (PubMed: 30112250)
- Sci Rep (2023): Wnt activation as a potential therapeutic approach to treat partial limbal stem cell deficiency. (PubMed: 37735479)
- Sci Rep (2021): Wnt6 plays a complex role in maintaining human limbal stem/progenitor cells. (PubMed: 34686698)
