Virus-Engineered Microsol Electrospun Scaffold Promotes the Reprogramming of Fibroblasts to Neurons
Virus-Engineered Microsol Electrospun Scaffold Promotes the Reprogramming of Fibroblasts to Neurons
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DOI：
10.1002/adfm.202301897
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发表时间：
2023-07-07
影响因子：
19
通讯作者：
Shi，Qin
中科院分区：
文献类型：
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作者：
Liu，Changpeng;Zhang，Xiongjinfu;Shi，Qin
广泛用于治疗各种疾病的基于慢病毒载体的疗法由于释放爆发、快速清除和免疫激活而面临限制。在本文中，提出了一种利用病毒工程化微溶胶电纺支架的慢病毒载体递送平台。鉴定脊髓损伤（SCI）大鼠中聚嘧啶束结合蛋白1（PTB）的显著上调，构建支架，其包含包封脑源性神经营养因子（BDNF）的透明质酸（HA）核心和聚多巴胺（PDA）修饰的线性聚-L-乳酸（PLLA）壳，其中shPTB慢病毒载体（LV-shPTB）经由PDA移植。在体外，LV‐shPTB实现了70%的感染效率，定向支架显著降低了炎症因子的表达，诱导成纤维细胞重编程为神经元，并维持BDNF的释放超过2周。在体内，支架提供物理支持和神经引导，以及释放的BDNF和LV‐shPTB。LV‐shPTB的递送导致成纤维细胞重编程为神经元，而持续的BDNF递送维持神经元的增殖和生长，这进一步促进了SCI大鼠神经功能的恢复。这些结果证明了病毒工程递送平台在SCI治疗和其他医学领域的潜在应用。
Lentiviral‐vector‐based therapies, widely used for treating various diseases, face limitations because of release burst, rapid clearance, and immune activation. Herein, a lentiviral vector delivery platform is proposed utilizing a virus‐engineered microsol electrospun scaffold. Identifying a remarkable upregulation of polypyrimidine tract binding protein1 (PTB) in spinal cord injury (SCI) rats, a scaffold is constructed comprising a hyaluronic acid (HA) core encapsulating brain‐derived neurotrophic factor (BDNF) and a polydopamine (PDA)‐modified linear poly‐l‐lactic acid (PLLA) shell, with shPTB lentiviral vectors (LV‐shPTB) grafted via PDA. In vitro, the LV‐shPTB achieves an infection efficiency of 70%, and the oriented scaffolds significantly reduce the expression of inflammatory factors, induce the reprogramming of fibroblasts into neurons, and sustain the release of BDNF for over 2 weeks. In vivo, the scaffolds provide physical support and neural guidance, as well as released BDNF and LV‐shPTB. LV‐shPTB delivery leads to the reprogramming of fibroblasts into neurons, and the sustained BDNF delivery maintains the neurons’ proliferation and growth, which further promotes the recovery of neurological function in SCI rats. These results demonstrate the potential application of virus‐engineered delivery platforms in SCI treatment and other medical fields.