**2. Cell-based therapies**

Several cell-based therapies are already approved for treatment in clinical settings [10–13]. These include resurfacing the cornea with limbal epithelial cells. Cellular therapy of corneal stroma has gained attention in recent years. Studies revealed that mesenchymal stromal (or stem) cells (MSCs) could survive and differentiate into adult human keratocytes in animal models without eliciting an inflammatory response. In addition, they produced new collagen in the host stroma and were able to remodel scars and improve transparency in animal models for corneal dystrophies [14, 15]. Cell-based therapies can be broadly divided into using stem cells to stimulate regeneration with and without scaffolds. This section focuses on stem-cell-based theories with scaffolds or templates.

Bio-fabrication of stem cell supports from silk fibroin/gelatin (SF/G) film and scaffold to make stem-cell-incorporating corneal epithelial and stromal equivalents for canine corneal regeneration. Canine limbal epithelial stem cells (cLESCs) were seeded in SF/G film, and canine corneal stromal stem cells (cCSSCs) were seeded in SF/G scaffold, respectively, which supported cell adhesion, viability, and proliferation along with differentiation of cLESCs and cCSSCs into keratocytes. Studies revealed endogenous ECM production after 14 days, thus mimicking native cornea [16]. Pitarresi and coworkers were the first ones to use hydrogels based on hyaluronic acid (HA) cross-linked with polyaspartamide derivative (PHEA-EDA) as an alternative to amniotic membrane for the delivery of limbal stem cells (LSCs). HA/PHEA-EDA hydrogel showed biocompatibility with immortalized human corneal epithelial cells or primary cells but only moderate to poor cell adhesion capabilities. These features

*Advances in Biomaterials for Corneal Regeneration DOI: http://dx.doi.org/10.5772/intechopen.106966*

allow the potential for clinical application of HA/PHEA-EDA as a delivery substrate with easy release of transplanted limbal stem cells to treat damaged corneas [17]. HCECs and human adipose stem cells (HASCs) were co-cultured in 3D hyaluronic acid hydrogel with and without collagen. HASCs could proliferate and differentiate within the proper cell density, and the survival of cells was better in the absence of collagen, showing potential for use in ocular surface reconstruction [18]. Hyaluronan hydrogel scaffold was used to expand human corneal epithelial stem cell ex-vivo in the xeno-free environment. The developed hydrogel behaved as native cornea equivalent, which reduced the risk of xeno-contamination and allowed the expansion of limbal stem cells [19].
