Results of a phase I/II clinical trial: standardized, non-xenogenic, cultivated limbal stem cell transplantation

Abstract

Background: To determine if a standardized, non-xenogenic, reduced manipulation cultivation and surgical transplantation of limbal stem cell grafts is a safe and effective treatment option for patients with total and partial limbal stem cell deficiency. Methods: In vitro cellular outgrowth and phenotype of the limbal epithelial cell and composite grafts were validated using a new protocol. Patients received either autologous (n = 15) or allogenic (n = 3) explants cultured using a standardized protocol free from xenogenic products. The resulting grafts were transplanted using a reduced manipulation surgical technique.

Stem Cell Therapies in Clinical Trials: Progress and Challenges

“…However, a recent study on allografts in Aniridia and Stevens-Johnson Syndrome that used a defined outcomes set procedure for cultured limbal cell epithelium transplants for bilateral limbal cell deficiency showed improvements in epithelial integrity and visual acuity up to 12 months but then a gradual decline over 3 years (Shortt et al, 2014). Typically restoration of the corneal epithelium can now be achieved in the majority (67%) of auto-and allogeneic transplants for partial and total limbal stem cell deficiency without easily detectable alteration to visual acuity (Zakaria et al, 2014).…”

Systematic Review and Meta-analysis on Transplantation of Ex Vivo Cultivated Limbal Epithelial Stem Cell on Amniotic Membrane in Limbal Stem Cell Deficiency

“…32 The expression of specific markers, such as stem cell-positive markers (p63, ABCG2, and K19) and the differentiation markers (K3/K12), was detected in the same culture. 26,[30][31][32][33]36 Expression of more K19 and less K3/K12 in the basal layer of the cultured cells was reported in several studies. 30,32,36 The colony-forming efficiency of representative cultures, which was used to analyze the presence of stem cells, resulted in a proportion varying from 2% to 9%.…”

“…Screening of live donors was reported in 5 of 8 studies, 34,35,37,38,42 which used living allogeneic limbal cells. That corneas from deceased donors were used as a source of limbal stem cells for culture 30,31,33,34,36,41 was not explicitly stated whether these were screened. Additionally, 4 of 18 studies 29-31,42 explicitly stated human amniotic membrane screening.…”

“…43 The use of ex vivo cultured LESCs to treat corneal LSCD in humans was first described by Pellegrini et al 44 in 1997. Subsequently, plenty of case series and reviews have reported the efficiency and evidence of this treatment. 12,[25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][45][46][47] However, with the lack of sufficient cases or valid measurements, they failed to provide a convincing assessment of this surgery. Moreover, there is controversy regarding the clinical outcome between different sources of limbal stem cells, such as autograft and allograft.…”

“…may be used as a cell substrate in the ex vivo culture. But human amniotic membrane (HAM), which promotes epithelialization, inhibits fibrosis, has anti-inflammatory and antiangiogenic properties, and possesses antimicrobial and antiviral properties and a high hydraulic conductivity, 22,23 with low or no immunogenicity, 24 has become the widely used material [25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42] acting as a surrogate environmental stem cell niche. 43 The use of ex vivo cultured LESCs to treat corneal LSCD in humans was first described by Pellegrini et al 44 in 1997. Subsequently, plenty of case series and reviews have reported the efficiency and evidence of this treatment.…”