STEM CELL THERAPIES have evolved significantly since the discovery of stem cells over half a century ago, with at least 5,000 clinical trials currently registered on ClinicalTrials.gov (Petrosyan et al, 2022; Wills et al, 2023). These therapies have garnered interest across all fields of medicine for their incredible potential in tissue regeneration, propelling them to the forefront of personalized health care. They have shown great promise in treating ocular degenerative diseases.
Stem cells possess highly unique properties that enable them to self-renew and differentiate into different cell types. This makes them capable of replenishing or repairing cells and tissues that may have been damaged by injury or disease.
A clear ocular application for these cell therapies includes replacing damaged cells, whether that damage was from external sources or inherited diseases (Sotiropulos et al, 2022). However, methods to transplant stem cells efficiently and effectively into the eye are still being extensively explored, and there are no regulated and approved strategies to perform these therapies on patients.
Contact lenses have been tested as a delivery device for numerous therapeutics and investigated as a platform for the direct delivery of stem cells to treat diseases of the cornea (Bobba and Di Girolamo, 2016). In the case of limbal stem cell deficiency (LSCD), the corneal epithelium cannot adequately repopulate due to the lack of limbal stem cells (LSCs) (Haagdorens et al, 2016). Conventional corneal repair strategies involve corneal grafts, whereby the damaged cornea is replaced with that of a healthy donor that contains LSCs.
Unfortunately, this method is typically difficult and is also ineffective in treating severely damaged corneas due to the insufficient numbers of LSCs transferred (Yin and Jurkunas, 2018; Singh and Sangwan, 2021). Stem cell-loaded contact lenses may provide a simple solution for transferring more LSCs to the ocular surface.
Functionalized and modified contact lenses have been demonstrated to support the growth and proliferation of stem cells on their surface, and evidence suggests that stem cells can migrate from the contact lens to a damaged cornea to assist in corneal repair (Di Girolamo et al, 2009). The advantages of this approach are vast, including that it is a simple, minimally invasive procedure that can be performed using the patient’s stem cells, reducing the risk of rejection.
Despite this, there is still limited transfer efficiency of LSCs to the cornea with contact lens-based methods (Brown et al, 2014). Efforts have been made to maximize the number of LSCs loaded onto contact lenses and then make it to the ocular surface, but these numbers are limited by both the contact lens size and hydrogel chemistry (Brown et al, 2014).
Advancements in contact lens drug delivery systems have yielded important findings that can be utilized in the delivery of stem cells. For instance, biodegradable contact lenses could provide a more active way to release cells to the cornea, compared to previous methods that relied on passive migration of the cells from the contact lens and their adherence to the ocular surface.
Biodegradable hydrogels can also be synthesized with regions that house and protect the stem cells while simultaneously increasing the total cell numbers, unlike those that were cultured solely on the surface of the contact lens (Sivaraj et al, 2021). Finally, new modifications to existing hydrogels are already being used to enhance the cell density in hydrogels and promote proper cellular phenotypes required for successful cellular transplantation. One example is an improved form of the biocompatible and polymeric hydrogel composed of gelatin methacrylate (GelMA) that was designed for corneal tissue engineering applications (Rizwan et al, 2017).
Cell-based therapies have proven to be effective for corneal injuries and disease. With great strides in hydrogel fabrication approaches, particularly in 3D bioprinting, a hydrogel device that supports stem cell growth and delivery is likely within reach. Engineered contact lenses that support the growth of cells and their delivery to the ocular surface hold great promise as an alternative to current methods of restoring vision in patients with damaged corneas.
REFERENCES
1. Petrosyan A, Martins PN, Solez K, Uygun BE, Gorantla VS, Orlando G. Regenerative medicine applications: An overview of clinical trials. Front Bioeng Biotechnol. 2022 Nov 25;10:942750.
2. Wills CA, Drago D, Pietrusko RG. Clinical holds for cell and gene therapy trials: Risks, impact, and lessons learned. Mol Ther Methods Clin Dev. 2023 Oct 20;31:101125.
3. Sotiropulos K, Kourkoutas D, Almaliotis D, Ploumidou K, Karampatakis V. Ocular stem cells: a narrative review of current clinical trials. Int J Ophthalmol. 2022 Sep 18;15:1529-1537.
4. Bobba S, Di Girolamo N. Contact Lenses: A Delivery Device for Stem Cells to Treat Corneal Blindness. Optom Vis Sci. 2016 Apr;93:412-418.
5. Haagdorens M, Van Acker SI, Van Gerwen V, et al. Limbal Stem Cell Deficiency: Current Treatment Options and Emerging Therapies. Stem Cells Int. 2016;2016:9798374.
6. Yin J, Jurkunas U. Limbal Stem Cell Transplantation and Complications. Semin Ophthalmol. 2018;33(1):134-141.
7. Singh A, Sangwan VS. Mini-Review: Regenerating the Corneal Epithelium With Simple Limbal Epithelial Transplantation. Front Med (Lausanne). 2021 May 28;8:673330.
8. Di Girolamo N, Bosch M, Zamora K, Coroneo MT, Wakefield D, Watson SL. A contact lens-based technique for expansion and transplantation of autologous epithelial progenitors for ocular surface reconstruction. Transplantation. 2009 May 27;87:1571-1578.
9. Brown KD, Low S, Mariappan I, et al. Plasma Polymer-Coated Contact Lenses for the Culture and Transfer of Corneal Epithelial Cells in the Treatment of Limbal Stem Cell Deficiency. Tissue Eng Part A. 2014 Feb 1;20:646-655.
10. Sivaraj D, Chen K, Chattopadhyay A, et al. Hydrogel Scaffolds to Deliver Cell Therapies for Wound Healing. Front Bioeng Biotechnol. 2021 May 3;9:660145.
11. Rizwan M, Peh GSL, Ang H-P, et al. Sequentially crosslinked bioactive hydrogels as nano-patterned substrates with customizable stiffness and degradation for corneal tissue engineering applications. Biomaterials. 2017 Mar:120:139-154.