Abstract
The use of advanced therapies with stem cells to reconstruct the complex tissue of corneal stroma has gained interest in recent years. Besides, collagen-based scaffolds bioengineering has been offered as another alternative over the last decade. The outcomes of the first clinical experience with stem cells therapy on corneal stroma regeneration in patients with advanced keratoconus were recently reported. Patients were distributed into three experimental groups: Group 1 (G-1) patients underwent implantation of autologous adipose-derived adult stem cells (ADASCs) alone, Group 2 (G-2) received a 120 μm decellularized donor corneal stromal laminas, and Group 3 (G-3) received a 120 μm recellularized donor laminas with ADASCs. A follow up of 36 months of clinical data, and 12 months of confocal microscopy study was performed, the authors found significant clinical improvement in almost all studied mean values of primary and secondary outcomes. Corneal confocal microscopy demonstrated an increase in cell density in the host stroma, as well as in the implanted tissue. Using different approaches, allogenic small incision lenticule extraction (SMILE) implantation was applied in cases with advanced keratoconus. Some authors reported the implantation of SMILE intrastromal lenticules combined with accelerated collagen cross-linking. Others performed intrastromal implantation of negative meniscus-shaped corneal stroma lenticules. Others have compared the outcomes of penetrating keratoplasty (PKP) vs. small-incision Intralase femtosecond (IFS) intracorneal concave lenticule implantation (SFII). Femtosecond laser-assisted small incision sutureless intrasotromal lamellar keratoplasty (SILK) has been also investigated. The published evidence shows that the implantation of autologous ADASCs, decellularized or recellularized human corneal stroma, allogenic SMILE lenticules corneal inlay, and recombinant cross-linked collagen have shown initially to be potentially effective for the treatment of advanced keratoconus. In light of the present evidence available, it can be said that the era of corneal stromal regeneration therapy has been already started.
Highlights
Cellular therapy and tissue engineering of the corneal stroma has gained interest over the last decade as a potential alternative treatment for corneal stroma diseases, such as corneal scarring, dystrophies, and ectasias, such as keratoconus (1).the highly complex structure of the corneal stroma, which involves very specific considerations concerning transparency, biomechanics, and optical behavior related to its very particular anatomical features (2), limits the usefulness of many of these corneal substitutes generated in preclinical experimental studies in the real clinical practice (3)
All cases presented an improvement in their Unaided distance visual acuity (UDVA) of (0.08, 0.14, 0.12), in their corrected distance visual acuity (CDVA) of (0.11, 0.2, 0.18) (Figure 3A), and rigid contact lens distance visual acuity (CLDVA) of (0.11, 0.19, 0.23) (Figure 3B), in decimal lines mean value equivalents in LogMar scale at [6, 12], and 36 months of follow up (14)
Autologous adipose-derived adult stem cells (ADASCs) Implantation Morphological results demonstrated that ADASCs appeared rounded in shape, more voluminous, and refringent than the host corneal keratocytes up to 6 months post-operative
Summary
Cellular therapy and tissue engineering of the corneal stroma has gained interest over the last decade as a potential alternative treatment for corneal stroma diseases, such as corneal scarring, dystrophies, and ectasias, such as keratoconus (1).the highly complex structure of the corneal stroma, which involves very specific considerations concerning transparency, biomechanics, and optical behavior related to its very particular anatomical features (2), limits the usefulness of many of these corneal substitutes generated in preclinical experimental studies in the real clinical practice (3). The first human clinical trials using an extraocular source of MSCs for corneal stem cell therapy in advanced keratoconus cases were performed and reported recently by our group (1, 10– 14), based on previous successful animal studies performed in part by the same research group (4, 5) In such preclinical studies, it has been shown that adult MSCs from human adipose tissue is an ideal source since they satisfy many requirements, such as easy access, high cell retrieval efficiency, and high differentiation capacity. More than a decade ago, we found that h-ADASCs transplanted into damaged rabbit corneas were able to differentiate into corneal keratocytes and produced collagen and keratocan which are characteristics of the corneal stroma (4) To provide such collagen in an adequate volume to restore corneal thickness, protocols have been used to obtain corneal decellularized matrices as they provide a more natural environment for the growth and differentiation of MSCs compared to synthetic scaffolds (8, 15, 16). We were able to demonstrate that the implanted cells survive at least 12 weeks after transplantation and they differentiate into human keratocytes in the experimental animal model (16)
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