Grosskopf Abigail K, Roth Gillie A, Smith Anton A A, Gale Emily C, Hernandez Hector Lopez, Appel Eric A
Department of Chemical Engineering Stanford University Stanford California.
Department of Bioengineering Stanford University Stanford California.
Bioeng Transl Med. 2019 Oct 22;5(1):e10147. doi: 10.1002/btm2.10147. eCollection 2020 Jan.
Stem cell therapies have emerged as promising treatments for injuries and diseases in regenerative medicine. Yet, delivering stem cells therapeutically can be complicated by invasive administration techniques, heterogeneity in the injection media, and/or poor cell retention at the injection site. Despite these issues, traditional administration protocols using bolus injections in a saline solution or surgical implants of cell-laden hydrogels have highlighted the promise of cell administration as a treatment strategy. To address these limitations, we have designed an injectable polymer-nanoparticle (PNP) hydrogel platform exploiting multivalent, noncovalent interactions between modified biopolymers and biodegradable nanoparticles for encapsulation and delivery of human mesenchymal stem cells (hMSCs). hMSC-based therapies have shown promise due to their broad differentiation capacities and production of therapeutic paracrine signaling molecules. In this work, the fundamental hydrogel mechanical properties that enhance hMSC delivery processes are elucidated using basic models. Further, studies in immunocompetent mice reveal that PNP hydrogels enhance hMSC retention at the injection site and retain administered hMSCs locally for upwards of 2 weeks. Through both and experiments, we demonstrate a novel scalable, synthetic, and biodegradable hydrogel system that overcomes current limitations and enables effective cell delivery.
干细胞疗法已成为再生医学中治疗损伤和疾病的有前景的治疗方法。然而，通过治疗性方式递送干细胞可能会因侵入性给药技术、注射介质的异质性和/或注射部位细胞留存率低而变得复杂。尽管存在这些问题，但在盐溶液中进行推注注射或植入载有细胞的水凝胶的传统给药方案已经凸显了细胞给药作为一种治疗策略的前景。为了解决这些局限性，我们设计了一种可注射的聚合物 - 纳米颗粒（PNP）水凝胶平台，该平台利用修饰的生物聚合物与可生物降解纳米颗粒之间的多价非共价相互作用来封装和递送人间充质干细胞（hMSCs）。基于hMSC的疗法因其广泛的分化能力和产生治疗性旁分泌信号分子而显示出前景。在这项工作中，使用基本模型阐明了增强hMSC递送过程的水凝胶基本力学性能。此外，在具有免疫活性的小鼠中的研究表明，PNP水凝胶可增强hMSC在注射部位的留存，并将给药的hMSC在局部留存长达2周以上。通过体外和体内实验，我们展示了一种新型的可扩展、合成且可生物降解的水凝胶系统，该系统克服了当前的局限性并实现了有效的细胞递送。
