Stem Cell Therapy for Corneal Epithelium Regeneration following Good Manufacturing and Clinical Procedures

Abstract

Objective. To evaluate outcomes of cultivated limbal epithelial transplantation (CLET) for management of ocular surface failure due to limbal stem cell deficiency (LSCD). Design. Prospective, noncomparative, interventional case series and extensive comparison with recent similar studies. Participants. Twenty eyes with LSCD underwent CLET (11 autologous; 9 allogeneic) and were followed up for 3 years. Etiologies were divided into 3 prognostic categories: Group 1, chemical injuries (7 eyes); Group 2, immune-based inflammation (4 eyes); and Group 3, noninflammatory diseases (9 eyes). Intervention. Autologous and allogeneic limbal epithelial cells were cultivated on amniotic membranes and transplanted. Evaluations were based on clinical parameters, survival analysis, and in vivo confocal microscopy (IVCM). European Union Tissues/Cells Directive and good manufacturing procedures were followed. Main Outcome Measures. Improved clinical parameters, absence of epithelial defects, and improved central corneal epithelial phenotype. Results. Success rate was 80% at 1-2 years and 75% at 3 years. Autografts and allografts had similar survival. Success rate was significantly lower in prognostic Group 1 (42.9%) than in Groups 2-3 (100% each). All clinical parameters improved substantially. By IVCM, 80% of cases improved in epithelial status. Conclusions. CLET improved corneal epithelium quality, with subsequent improvement in symptoms, quality of life, and vision. These results confirm that CLET is a valid therapy for ocular surface failure.

Diagnostic criteria for limbal stem cell deficiency before surgical intervention—A systematic literature review and analysis

“…Surgical treatment of LSCD had been offered at 66 eye centers in 23 countries in Europe, Asia, North America, and South America (Table 1). Of the 131 studies, 5 were uncontrolled clinical trials, 18,42,62,113,158 29 were prospective studies, 3,13,17,28,35,47,48,64,72,73,75,76,81,97,100,103,104,109,112,114,121,125,129,130,136,137,144,146,157 and 73 were retrospective studies. 1,2,5,7e12,14e16,20,24e26,31,32,39e41, 43,45,46,49,51e54,57,60,61,63,65,70,71, 77,78,83e91,95,98,99,106,108,116,118e120,122,123,126e128,131e135,139e142,147, 150,153,154 In the remaining 24 studies 6,29,37,38, 44,50,55,56,59,74,80,88,96,105,107,117,…”

“…5,7,8, 65,71,77,78,99,132,134,143,158 IVCM was used in only 4 studies (66 eyes), all of which were performed by institutions in Europe. The presence of conjunctiva-like or mixed epithelial cell phenotype in the central cornea was used as the supporting evidence in 3 studies, 42,109,127 and the detection of goblet cells on the cornea was used to confirm the LSCD diagnosis in 1 study. 98…”

Clinical Outcomes From Cultivated Allogenic Stem Cells vs. Oral Mucosa Epithelial Transplants in Total Bilateral Stem Cells Deficiency

“…The tissue from a cadaveric donor was obtained within 24 h (22) to 7 days post-mortem (28). One study obtained cadaveric tissue within 2-3 weeks before the planned allogenic CLET procedure (24).…”

Poly-l/dl-lactic acid films functionalized with collagen IV as carrier substrata for corneal epithelial stem cells

“…Cultivated limbal epithelial transplantation (CLET) for reconstruction of the damaged ocular surface in LSCD syndrome was first reported in 1997 [6]. Subsequently, this strategy has been used by many other authors [7][8][9][10]. To perform CLET, a substratum is necessary for both in vitro expansion of epithelial cells and the subsequent transplantation onto the ocular surface.…”

“…To perform CLET, a substratum is necessary for both in vitro expansion of epithelial cells and the subsequent transplantation onto the ocular surface. Biological substrata such as fibrin [9,11], human amniotic membrane [10,[12][13][14], and cellular feeder layers such as 3T3 fibroblasts [6] have been used to facilitate the expansion of corneal epithelial cells. However, as natural products, none of these agents can be standardized, and they are not optically transparent.…”