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

I-Corps项目更广泛的影响/商业潜力是开发一种可扩展和可控的由天然聚合物组成的聚合物涂层，用于制造与治疗相关的人类间充质间质细胞（hMSCs）。造血干细胞疗法已经显示出治愈致命疾病的潜力。然而，造血干细胞治疗需要大量的高效细胞。hmsc的工业规模制造依赖于从供体中提取细胞，并在生物反应器中扩增/繁殖细胞。所提出的技术可以应用于目前hMSC制造行业中使用的生物反应器系统，并且可以在提高其产量的同时增加hMSC的治疗潜力。此外，这些技术可能有助于hMSCs衍生产品的质量和细胞扩增过程中hMSCs的活力。如果成功，所提出的技术可能会改善hMSC的制造过程，从而为患者提供更容易获得的hMSC治疗。I-Corps项目的基础是开发一种表面涂层，以促进人类间充质间质细胞（hMSC）生产的可扩展和可控环境，并改善细胞制造过程。目标是改善hMSC在小型和大型扩展平台中的行为和功能，以提高最终用户的细胞质量。所提出的涂层由胶原蛋白和肝素组成，并通过逐层组装过程构建，已被证明支持hMSC培养并提高细胞活力。该技术可应用于平面和球形微载体。微载体用于悬浮型hMSC培养。当提议的涂层与可溶性干扰素结合时，hMSCs的免疫抑制特性显着增强，产生更有效的治疗产品。该技术提高了细胞的活力，并根据免疫调节活性改善了细胞的行为和质量。此外，该技术可调节hMSC细胞对可溶性因子的反应，提高其免疫抑制潜能，从而提高细胞制造效率和细胞产品质量。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

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.