Applied Microbiology Research Center, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran.
J Cell Physiol. 2019 Apr;234(4):4970-4986. doi: 10.1002/jcp.27298. Epub 2018 Sep 14.
Mesenchymal stem cells (MSCs)-based regenerative therapy is now considered as an alternative approach to revive infectious diseases, including sepsis. Nevertheless, the efficiency of MSC application is limited by the poor survival rate of engrafted MSCs. Hence, preconditioning was established as a strategy to increase the cells' efficiency.
MSCs were preconditioned with 1 μg/ml of three different lipopolysaccharides (LPSs) of Pseudomonas (Pse-LPS), Acinetobacter (Ac-LPS), and Acinetobacter inactivated lipid A by PagL (Ac-LPS-PagL). Then, preconditioned MSCs were exposed to oxidative stress and serum deprivation followed by evaluation of the antibacterial activity, survival, and apoptosis of MSCs. Then, the murine sepsis model treated with 100 μl phosphate-buffered saline (control group, sepsis group), 100 μl of 1 × 10 wild MSCs (MSC group), and three remained groups received 100 μl of 1 × 10 LPS-preconditioned MSCs (Pse-LPS-MSCs group: LPS purified from Pseudomonas, or Ac-LPS-MSCs group: LPS purified from Acinetobacter, and Ac-PagL-LPS-MSCs group: detoxified LPS Pagl).
After 4 days, LPS-preconditioned MSC transplantation modulated the immune response and reduced inflammation in septic mice. Apoptosis of Pse-LPS/Ac-LPS-preconditioned-MSCs was obviously reduced in vitro, and the survival rate of engrafted mice was evidently elevated in Pse-LPS-MSCs and Ac-LPS-MSCs groups compared with other three groups.
LPS preconditioning provides an innovative strategy for evolving functional and biological properties of MSCs and ameliorates the survival rate of the mouse model of sepsis after MSC transplantation, protects cells from apoptosis and organ damages, and evaluates therapeutic properties, including immunemodulatory.
间充质干细胞（MSCs）再生治疗目前被认为是一种替代方法，可用于治疗包括败血症在内的传染病。然而，MSCs 的应用效率受到植入 MSCs 存活率低的限制。因此，预处理被确立为一种提高细胞效率的策略。
将 MSCs 用 1μg/ml 的三种不同的绿脓假单胞菌（Pse-LPS）、不动杆菌（Ac-LPS）和 PagL 失活脂 A 的 Acinetobacter LPS（Ac-LPS-PagL）预处理。然后，预处理后的 MSCs 暴露于氧化应激和血清剥夺，随后评估 MSCs 的抗菌活性、存活和凋亡。然后，用 100μl 磷酸盐缓冲盐水（对照组，败血症组）、100μl 1×10 野生 MSCs（MSC 组）和其余三组中的三组（Pse-LPS-MSCs 组：来自 Pseudomonas 的 LPS 纯化，或 Ac-LPS-MSCs 组：来自 Acinetobacter 的 LPS 纯化，和 Ac-PagL-LPS-MSCs 组：脱毒 LPS Pagl）处理 100μl 预处理的 LPS-MSCs 治疗小鼠败血症模型。
4 天后，LPS 预处理 MSC 移植调节了败血症小鼠的免疫反应并减轻了炎症。Pse-LPS/Ac-LPS 预处理-MSCs 的体外凋亡明显减少，与其他三组相比，Pse-LPS-MSCs 和 Ac-LPS-MSCs 组中植入小鼠的存活率明显提高。
LPS 预处理为改善 MSCs 的功能和生物学特性提供了一种创新策略，并提高了 MSC 移植后败血症小鼠的存活率，保护细胞免受凋亡和器官损伤，并评估了免疫调节等治疗特性。
