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Rapid Heterotrophic Ossification with Cryopreserved Poly(ethylene glycol-) Microencapsulated BMP2-Expressing MSCs

机译:冷冻保存的聚乙二醇微囊化表达BMP2的MSC的快速异化骨化

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摘要

Autologous bone grafting is the most effective treatment for long-bone nonunions, but it poses considerable risks to donors, necessitating the development of alternative therapeutics. Poly(ethylene glycol) (PEG) microencapsulation and BMP2 transgene delivery are being developed together to induce rapid bone formation. However, methods to make these treatments available for clinical applications are presently lacking. In this study we used mesenchymal stem cells (MSCs) due to their ease of harvest, replication potential, and immunomodulatory capabilities. MSCs were from sheep and pig due to their appeal as large animal models for bone nonunion. We demonstrated that cryopreservation of these microencapsulated MSCs did not affect their cell viability, adenoviral BMP2 production, or ability to initiate bone formation. Additionally, microspheres showed no appreciable damage from cryopreservation when examined with light and electron microscopy. These results validate the use of cryopreservation in preserving the viability and functionality of PEG-encapsulated BMP2-transduced MSCs.
机译:自体骨移植是长骨骨不连的最有效治疗方法,但它对捐献者构成了相当大的风险,因此有必要开发替代疗法。聚乙二醇(PEG)微囊化和BMP2转基因传递正在共同发展,以诱导迅速的骨形成。但是,目前缺乏使这些治疗可用于临床的方法。在本研究中,我们使用间充质干细胞(MSC),因为它们易于收获,具有复制潜力和具有免疫调节功能。 MSC来自绵羊和猪,原因是它们作为骨骼不愈合的大型动物模型具有吸引力。我们证明了冷冻保存这些微囊化的MSC不会影响其细胞生存能力,腺病毒BMP2的产生或启动骨形成的能力。另外,当用光学和电子显微镜检查时,微球没有显示出因冷冻保存而引起的明显损坏。这些结果验证了冷冻保存在保存PEG包被的BMP2转导的MSC的活力和功能中的用途。

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