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

这个i-Corps项目的更广泛的影响/商业潜力是开发一种由天然聚合物组成的可伸缩和可控的聚合物涂层，用于制造与治疗相关的人类间充质基质细胞(HMSCs)。人类骨髓间充质干细胞疗法已显示出治愈致命疾病的潜力。然而，hMSC的治疗需要大量的高潜能细胞。工业化生产hMSCs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。建议的技术可以应用于目前用于hMSC制造业的生物反应器系统，并可能在提高hMSCs产量的同时增加hMSCs的治疗潜力。此外，这些技术可能有助于hMSC衍生的产品质量和hMSCs在细胞扩增过程中的生存能力。如果成功，建议的技术可能会改进hMSC的制造工艺，为患者带来更容易获得的hMSC治疗。这个i-Corps项目的基础是开发一种表面涂层，以促进可扩展和可控制的环境来生产人类间充质基质细胞(HMSC)，并改进细胞制造工艺。目标是改善hMSC在小型和大型扩展平台中的行为和功能，以提高终端用户的小区质量。建议的涂层由胶原和肝素组成，通过逐层组装工艺构建，已被证明支持hMSC培养和提高细胞活力。该技术既适用于平面微载体，也适用于球形微载体。微载体用于悬浮培养人骨髓间充质干细胞。当建议的涂层与可溶性干扰素伽马结合时，hMSCs的免疫抑制性能显著增强，产生更有效的治疗产品。这项技术提高了细胞的活力，并基于免疫调节活性改善了它们的行为和质量。此外，拟议的技术调节hMSC细胞对可溶性因素的反应并提高其免疫抑制潜力，这可能导致更高效的细胞制造和更高质量的细胞产品。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势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.