I-Corps: Polyelectrolyte multilayered surfaces for use in human mesenchymal stem/stromal cells (hMSC) manufacturing

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The broader impact/commercial potential of this I-Corps project is the development of a scalable and controllable polymeric coating composed of natural polymers to be used during the manufacture of therapeutically-relevant human mesenchymal stromal cells (hMSCs). hMSC therapies have shown potential to cure deadly diseases. However, hMSC treatments require large quantities of highly potent cells. Industrial-scale manufacturing of hMSCs relies upon extracting cells from a donor and expanding/multiplying the cells in bioreactors. The proposed technology may be applied to current bioreactor systems used in the hMSC manufacturing industry and may increase the therapeutic potential of hMSCs while improving their yields. In addition, these technology may contribute to hMSC-derived product quality and the viability of hMSCs during cell expansion. If successful, the proposed technology may improve the hMSC manufacturing process leading to more accessible hMSC treatments for patients. This I-Corps project is based on the development of a surface coating to promote a scalable and controllable environment for the production of human mesenchymal stromal cells (hMSC) and improve the cell manufacturing process. The goal is to improve hMSC behavior and function in small and large-scale expansion platforms to improve the quality of cells for end users. The proposed coating is composed of collagen and heparin and is constructed via a layer-by-layer assembly process and has been shown to support hMSC culture and increase cell viability. The technology may be applied to both flat surfaces and spherical microcarriers. Microcarriers are used in suspension-based hMSC cultures. When the proposed coatings are combined with soluble interferon gamma, the immunosuppressive properties of hMSCs are significantly enhanced, yielding a more potent therapeutic product. This technology increases the cells' viability and improves their behavior and quality based on immunomodulatory activities. In addition, the proposed technology modulates the hMSC cells' response to soluble factors and improves their immunosuppressive potential, which may lead to more efficient cell manufacturing and a better quality cell product.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.