Hypothermically Stored Adipose-Derived Mesenchymal Stromal Cell Alginate Bandages Facilitate Use of Paracrine Molecules for Corneal Wound Healing

Abstract

Adipose-derived mesenchymal stromal cells (Ad-MSCs) may alleviate corneal injury through the secretion of therapeutic factors delivered at the injury site. We aimed to investigate the therapeutic factors secreted from hypothermically stored, alginate-encapsulated Ad-MSCs’ bandages in in vitro and in vivo corneal wounds. Ad-MSCs were encapsulated in 1.2% w/v alginate gels to form bandages and stored at 15 °C for 72 h before assessing cell viability and co-culture with corneal scratch wounds. Genes of interest, including HGF, TSG-6, and IGF were identified by qPCR and a human cytokine array kit used to profile the therapeutic factors secreted. In vivo, bandages were applied to adult male mice corneas following epithelial debridement. Bandages were shown to maintain Ad-MSCs viability during storage and able to indirectly improve corneal wound healing in vivo. Soluble protein concentration and paracrine factors such as TSG-6, HGF, IL-8, and MCP-1 release were greatest following hypothermic storage. In vivo, Ad-MSCs bandages-treated groups reduced immune cell infiltration when compared to untreated groups. In conclusion, bandages were shown to maintain Ad-MSCs ability to produce a cocktail of key therapeutic factors following storage and that these soluble factors can improve in vitro and in vivo corneal wound healing.

Developing a New Strategy for Delivery of Neural Transplant Populations Using Precursor Cell Sprays and Specialized Cell Media

“…Such an approach is being developed for non‐neural transplant transportation where a range of cells have been encapsulated in polymers. [ 32,33 ] This technology could be integrated into a spray device enabling sterile transportation and spraying using a single medical product. Further refinements to develop novel neurosurgical devices seem feasible.…”

Mesenchymal Stromal Cell–Based Therapy for Dry Eye: Current Status and Future Perspectives

“…It is known that AD-MSCs can produce paracrine factors, such as VEGF, IGF, and TGF-β, with the potential to improve tissue wound healing 80 , 81 . In the treatment of corneal injury, paracrine factors of AD-MSCs can promote corneal repair by reducing immune infiltration 82 . A study which cocultured AD-MSCs with human corneal epithelial cells found that AD-MSC secretions inhibited TGF-β-induced corneal epithelial–mesenchymal transition 83 .…”

Hypothermic Preservation of Adipose-Derived Mesenchymal Stromal Cells as a Viable Solution for the Storage and Distribution of Cell Therapy Products

“…Alginate is a natural polysaccharide that can be obtained from seaweed and jellified when cations are added to generate a biocompatible hydrogel [ 23 ]. The advantages of alginate as a simple and cost-effective solution for protecting cell products during storage and transportation have been attributed to its ability to stabilize the membrane of cells in suspension and to protect them from osmotic shock and mechanical stress [ 12 , 24 ]. Alginate encapsulation has potential to impact CGT manufacturing.…”