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Optimization and angiogenic assessment of macromolecular crowding in human umbilical cord mesenchymal stromal cell culture for the development of a wound healing cell therapy product.

The number of patients suffering from diabetes in 2019 was 463 million, and there will be 700 million adults with diabetes by 2045. Non-healing diabetic foot ulceration is a major complication of diabetes resulting in significant human suffering and is a major burden on healthcare system resources. 15% of diabetic patients will develop a foot ulcer and 12-25% of these patients will require amputation3. The cause of impaired wound healing in diabetic patients is multifactorial with contributions from high blood sugar, impaired blood flow and nerve damage. Therefore, developing a cell therapy product to heal the diabetic wound is an urgent issue.
Previous research has shown that using topical treatment of mesenchymal stromal cells (MSCs) in animal models greatly enhanced diabetic wound healing. However, direct cell injection may cause rapid cell death and poor cell localization. Macromolecular crowding has been shown to enhance cell matrix deposition in human stem/stromal cell cultures, without affecting how the cell behaves. By growing cells under macromolecular crowding conditions, there is potential to generate a cell sheet which has good cell localisation, high cell matrix deposition, no immune response and the ability to retain the cell function5. Carrageenan has been shown to be an effective macromolecular crowder used to enhance collagen deposition in MSC culture. However, the optimal concentration of carrageenan in umbilical cord derived mesenchymal stromal cells (UC-MSC) cultures has yet to been assessed. The blood vessel making capability of UC-MSC treated by the optimized macromolecular crowding is yet to be investigated.