A proof-of-concept clinical trial using mesenchymal stem cells for the treatment of corneal epithelial stem cell deficiency

Abstract

Ocular stem cell transplantation derived from either autologous or allogeneic donor corneoscleral junction is a functional cell therapy to manage extensive and/or severe limbal stem cell deficiencies that lead to corneal epithelial failure. Mesenchymal stem cells have been properly tested in animal models of this ophthalmic pathology, but never in human eyes despite their potential advantages. We conducted a 6-to 12month proof-of-concept, randomized, double-masked pilot trial to test whether allogeneic bone marrow-derived mesenchymal stem cell transplantation (MSCT, n=17) was as safe and as equally efficient as allogeneic cultivated limbal epithelial transplantation (CLET, n=11) to improve corneal epithelial damage due to limbal stem cell deficiency. Primary endpoints demanded combination of symptoms, signs, and the objective improvement of the epithelial phenotype in central cornea by in-vivo confocal microscopy. This proof-of-concept trial showed that MSCT was as safe and efficacious as CLET. Global success at 6-12 months was 72.7%-77.8% for CLET cases and 76.5%-85.7% for MSCT cases (not significant differences). Central corneal epithelial phenotype improved in 71.4% and 66.7% of MSCT and CLET cases, respectively at 12 months (p=1.000). There were no adverse events related to cell products. This trial suggests first evidence that MSCT facilitated improvement of a diseased corneal epithelium due to lack of its stem cells as efficiently as CLET. Consequently, not only CLET but also MSCT deserves more preclinical investigational resources before the favorable results of this proof-of-concept trial could be transformed into the larger numbers of the multicenter trials that would provide stronger evidence. (ClinicalTrials.gov number, NCT01562002.) 5 of 44 Key words: clinical trial, corneal blindness, corneal epithelial stem cells, human proof-of-concept, in vivo confocal microscopy, limbal stem cell deficiency, mesenchymal stem cell, stem cell transplantation of 44

Simultaneous in vivo PET/MRI using fluorine-18 labeled Fe3O4@Al(OH)3 nanoparticles: comparison of nanoparticle and nanoparticle-labeled stem cell distribution

“…Mesenchymal stem cells (MSCs) are multipotent stromal cells that have been shown to have high potential for disease treatment, e.g., Crohn's disease, ocular disorders, spinal cord injuries, and cartilage repair [1][2][3][4][5]. Furthermore, MSCs have been shown to target tumors and their microenvironment, and potentially play a role in tumor cell therapy [6,7].…”

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

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Recent Advances in Stem Cell Therapy for Limbal Stem Cell Deficiency: A Narrative Review

“…Among the several paracrine factors produced by MSCs, tumour necrosis factor-a-stimulated gene 6 (TSG-6) has been shown to be necessary for MSCs to deliver their anti-inflammatory effects [141]. An inhuman, proof-of-concept, randomised, doubleblind controlled trial demonstrated possible equivalency of allogeneic MSC therapy and allogeneic CLET in the treatment of bilateral stage II/III LSCD [142]. Primary end points included corneal epithelial opacification, integrity (presence of persistent defects), and cell morphology (as measured by IVCM).…”