Mesenchymal Stem Cells and Exosomes: A Novel Therapeutic Approach for Corneal Diseases

Abstract

The cornea, with its delicate structure, is vulnerable to damage from physical, chemical, and genetic factors. Corneal transplantation, including penetrating and lamellar keratoplasties, can restore the functions of the cornea in cases of severe damage. However, the process of corneal transplantation presents considerable obstacles, including a shortage of available donors, the risk of severe graft rejection, and potentially life-threatening complications. Over the past few decades, mesenchymal stem cell (MSC) therapy has become a novel alternative approach to corneal regeneration. Numerous studies have demonstrated the potential of MSCs to differentiate into different corneal cell types, such as keratocytes, epithelial cells, and endothelial cells. MSCs are considered a suitable candidate for corneal regeneration because of their promising therapeutic perspective and beneficial properties. MSCs compromise unique immunomodulation, anti-angiogenesis, and anti-inflammatory properties and secrete various growth factors, thus promoting corneal reconstruction. These effects in corneal engineering are mediated by MSCs differentiating into different lineages and paracrine action via exosomes. Early studies have proven the roles of MSC-derived exosomes in corneal regeneration by reducing inflammation, inhibiting neovascularization, and angiogenesis, and by promoting cell proliferation. This review highlights the contribution of MSCs and MSC-derived exosomes, their current usage status to overcome corneal disease, and their potential to restore different corneal layers as novel therapeutic agents. It also discusses feasible future possibilities, applications, challenges, and opportunities for future research in this field.

Keywords: cornea; corneal diseases; corneal regeneration; exosomes; mesenchymal stem cells.

Figure 1

Cornea can be damaged from both external and internal factors (chemical burns, trauma, intrinsic–corneal diseases) leading to impaired vision. Different approaches have been employed to improve the regeneration of the injured cornea. Utilizing MSCs (cell-based therapy) and their secretions (cell-free therapy) can restore the normal corneal function in the diseased/injured cornea.

Figure 2

MSCs for treating corneal diseases. MSCs are well known to have a therapeutic effect through paracrine secretions, and by making direct cell contacts with cells in different corneal layers, such as epithelium, stoma, and endothelium. This can help to promote the survival, growth, and specialization of cells, while reducing cell death, inflammation, and fibrosis.

Figure 3

Exosomes are capable of transferring bioactive molecules to recipient cells through three mechanisms: (a) intercellular signaling via receptor–ligand interaction, (b) endocytosis by recipient cells, and (c) direct fusion with the recipient cell membrane, leading to the release of their cargo into the target cells. These modes of transfer are the result of the biogenesis of exosomes [97,148].

Figure 4

(a) A schematic representation of the experimental administration of MSC-derived exosomes in cornea. (b) In the cornea, therapeutic molecules are delivered that inhibit angiogenesis, cell proliferation, cell migration, and differentiation. (c) Regeneration of corneal layers is observed after treatment with MSC-derived exosomes.