Autologous Adipose-Derived Adult Stem Cell Transplantation for Corneal Diseases — A-ADAS-CT-CD  

Keratoconus Clinical Trial

Official title: Autologous Adipose-Derived Adult Stem Cell Transplantation for Corneal Diseases

Status Recruiting

Clinical Trial Summary

Transplantation of cellularized human cornea impregnated and populated by mesenchymal stem cells derived from the patient's adipose tissue. The purpose of the study is to assess the safety, tolerability, and preliminary efficacy of transplantation of a single dose of autologous mesenchymal adipose tissue derived adult stem cells (ADAS) cellularized into laminas for subjects with corneal defects. 3 groups will be included in the study: (1) transplantation of ADAS alone without scaffold, (2) transplantation of scaffold (human corneal decellularized lamina) without ADAS, and (3) transplantation of ADAS cellularized on scaffold (the human corneal decellularized lamina)

Clinical Trial Description

Different types of stem cells have been used in various ways in several research projects in order to find the optimal procedure to regenerate the human corneal stroma. It included several approaches which can be classified as intrastromal implantation of stem cells (1) alone, (2) together with a biodegradable scaffold, (3) with a non-biodegradable scaffold, or (4) with a decellularized corneal stromal scaffold. In fact, the complex structure of the corneal stroma has not been yet replicated, and there are well known drawbacks to the use of synthetic scaffold-based designs. Recently, several corneal decellularization techniques have been described, which provide an acellular corneal extracellular matrix (ECM). These scaffolds have gained attention in the last few years as they provide a more natural environment for the growth and differentiation of cells when compared with synthetic scaffolds. In addition, components of the ECM are generally conserved among species and are tolerated well even by xenogeneic recipients. Keratocytes are essential for remodeling the corneal stroma and for normal epithelial physiology. This highlights the importance of transplanting a cellular substitute together with the structural support (acellular ECM) to undertake these critical functions in corneal homeostasis. To the best of the investigators knowledge, all attempts to repopulate decellularized corneal scaffolds have used corneal cells, but these cells have major drawbacks that preclude their autologous use in clinical practice (damage of the donor tissue, lack of cells and inefficient cell subcultures), thus the efforts to find an extraocular source of autologous cells. A recent study by the investigators has shown a perfect biointegration of human decellularized corneal stromal sheets (100µm thickness) with and without h-ADASC colonization inside the rabbit cornea in vivo, without observing any rejection response despite the graft being xenogeneic. The investigators also demonstrated the differentiation of h-ADASCs into functional keratocytes inside these implants in vivo, which then achieved their proper biofunctionalization. According to the investigator's opinion the transplant of stem cells together with decellularized corneal ECM would be the best technique to effectively restore the thickness of a diseased human cornea, like in keratoconus. Through this technique, and using extraocular mesenchymal stem cells from patients, it is possible to transform allergenic grafts into functional autologous grafts, theoretically avoiding the risk of rejection.

The process flow is defined as following: (1) the file study: which start by receiving the file of the patient, the file will be forwarded to appointed physicians coordinators for review and submission of medical report, then the medical report will be evaluated within the cell therapy committee and the patient will be asked for clinical examination, and after consultation a reply to the patient with medical decision will follow with an approval or not to be recruited and if yes, a brief report about the procedure will be submitted and explained in details to the patient, a consent form must be signed if the patient agree to be included in the study, (2) the patient admission: which may start by completion of the procedure forms and doing the pre-op evaluation (initial work up defined as a clinical and biological assessment upon C.A.S which may include unaided and best spectacle corrected visual acuity, refraction, slit lamp examination, intraocular pressure, fundoscopy, corneal topography, aberrometry, endothelial cell count (specular microscopy) as well as blood tests) by an ophthalmologist, followed by lipoaspiration of the subcutaneous adipose tissue to be performed by a plastic surgeon, then sample processing at a cGMP facility for isolation and characterization of the stromal vascular fraction enriched with ADAS as well as laminas preparing (the quality control assessment will be realized before and after all the steps of the procedure starting from the ADAS collection to transplantation including cell culture, cell quiescence, decellularization of human corneal lamina, recellularization of the laminas with ADAS, and transplantation; the assessment will include cell viability, cell number, cell apoptosis, immunophenotyping, infection, inflammation by analyzing the secreted cytokines from ADAS, lamina cutting, lamina thickness, immunostaining, confocal microscopy, etc.); (3) the delivery (transplantation) which starts by a peribulbar or retrobulbar anesthesia where the patient is placed under operating microscope, followed by a femtosecond laser assisted mid-stromal lamellar dissection, then the ADAS or laminas or recellularized laminas will be placed within the pocket, and finally closed by a superior incision closure. The patient will be putted under antibiotic/steroids for a defined period and followed by the team at 1 week, 2 weeks, 1 month, 3 months, 6 months and 1 year.

This protocol of cell therapy will be applied exclusively at Laser Vision (Hazmieh-Lebanon) and prepared at Reviva Regenerative Medicine Center in affiliation with VISSUM (Alicante-Spain) and Optica General (Saida-Lebanon).

The patient's recruitment will take place: for the lipoaspiration, processing, preparing the celluraized laminas and quality control assessments, at the Middle East Institute of Health the Reviva Center (Bsalim-Lebanon) under the regulations of the hospital and the Reviva Center; for injection, at Laser vision (Hazmieh-Lebanon); and for follow-up, at Laser vision & optica general. All these steps are managed by VISSUM (Prof. J. ALIO). ;

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Corneal Diseases
• Corneal Dystrophies, Hereditary
• Hereditary Corneal Dystrophy
• Keratoconus

• NCT number: NCT02932852
• Study type: Interventional
• Source: Vissum, Instituto Oftalmológico de Alicante
• Contact: Jorge Alio Sanz, MD, PhD
• Phone: +34 902333344
• Email: jlalio@vissum.com
• Status: Recruiting
• Phase: Phase 0
• Start date: November 2015