Stroke remains the leading cause of morbidity and mortality. Stem cell-based therapy offers promising hope for survivors and their families. Despite the clinical translation of stem cell-based therapies in stroke patients for almost two decades, results of these randomized controlled trials are not very optimistic. In these lines an amalgamation of nanocarriers based drug delivery with stem cells holds great promises in enhancement stroke recovery. In the present study, we employed Sivelestat loaded Nano Lipid Carriers to dental pulp stem cells and mesenchymal stem cells exposed to the oxygen-glucose treatment. Various physicochemical limitations associated with sivelestat applications and its recent inefficacy in the clinical trials necessitates the development of novel delivery approaches for sivelestat. Therefore, to improve its efficacy on the survival of DPSCs and MSCs cell types under oxygen-glucose deprivation treatment, the current NLCs were formulated and characterized. Resulting NLCs exhibited a hydrodynamic diameter of 160 - 180 nm by DLS technique and possessed good PDI values of 0.2 - 0.3. Their shape size and surface morphology were corroborated with microscopic techniques like TEM, SEM, and AFM. FTIR and UV-Vis techniques confirmed nanocarriers' loading capacity, encapsulation efficiency of sivelestat, and its release behavior. Oxidative stress in DPSCs and MSCs was assessed by DHE and DCFDA staining, and cell viability was assessed by Trypan blue exclusion test and MTT assay. Results indicated that Sivelestat loaded NLCs protected the loss of cell membrane integrity and restored cell morphology. Furthermore, NLCs successfully defended human DPSCs and MSCs against OGD induced oxidative and inflammatory stress. In conclusion, modulation of oxidative and inflammatory stress by treatment with sivelestat loaded nanocarriers in DPSCs and MSCs provides a novel strategy to rescue stem cells during ischemic stroke.

中风仍然是发病率和死亡率的主要原因。基于干细胞的疗法为幸存者及其家人带来了希望。尽管在卒中患者中基于干细胞疗法的临床翻译已有近二十年的历史，但这些随机对照试验的结果并不十分乐观。在这些研究中，基于纳米载体的药物与干细胞的融合将在提高卒中恢复方面具有广阔的前景。在本研究中，我们将Sivelestat负载的纳米脂质载体应用于暴露于氧-葡萄糖处理的牙髓干细胞和间充质干细胞。与ilelestat应用相关的各种物理化学局限性及其最近在临床试验中的无效性，都需要开发新颖的ilelestat递送方法。因此，为了提高其在氧葡萄糖剥夺处理下对DPSCs和MSCs细胞类型存活的功效，对当前的NLC进行了配制和表征。所得的NLC通过DLS技术显示出160-180nm的流体动力学直径，并具有0.2-0.3的良好PDI值。TEM，SEM和AFM等显微技术证实了它们的形状大小和表面形态。FTIR和UV-Vis技术证实了纳米载体的负载能力，西乐司他的包封效率及其释放行为。通过DHE和DCFDA染色评估DPSC和MSC中的氧化应激，并通过台盼蓝排除试验和MTT分析评估细胞活力。结果表明，载有Sivelestat的NLC保护了细胞膜完整性的丧失并恢复了细胞形态。此外，NLC成功防御了人DPSC和MSC抵抗OGD诱导的氧化应激和炎症应激。总之，通过在DPSCs和MSCs中用载有ilelestat的纳米载体处理来调节氧化应激和炎症应激，提供了一种在缺血性中风中拯救干细胞的新策略。