a Department of Biochemistry , Pasteur Institute of Iran , Tehran , Iran.
b Department of Clinical Research , Pasteur Institute of Iran , Tehran , Iran.
Artif Cells Nanomed Biotechnol. 2018;46(sup2):1178-1187. doi: 10.1080/21691401.2018.1481862. Epub 2018 Jun 22.
Systemic inflammatory response syndrome is a complex pathophysiologic and immunologic response to an insult. Sepsis is a life-threatening condition happening when the body's response to infection causes injury to its own tissues and organs. Stem cell therapy is a new approach to modulate immune responses. Mesenchymal stem cells (MSCs) establish a regenerative niche by secreting secretome and modulating immune responses. MSC secretome can be leveraged for therapeutic applications if production of secretary molecules were optimized. Pharmacological preconditioning using small molecules can increase survival of MSCs after transplantation. The aim of this study was to investigate the effect of secretome of human embryonic-derived mesenchymal stem cells (hESC-MSCs) preconditioned with MG-132,Trimetazidine (TMZ) and Diazoxide (DZ) on immunomodulatory efficiency of these cells in Lipo polysaccharide (LPS) challenged mice models. Mice were injected intraperitoneally with LPS and groups of animals were intraperitoneally given 1 ml 30× secretome 6 h after LPS injection. Serum levels of biochemical parameters were then measured by an auto analyser and serum inflammatory cytokine levels were analysed using commercially available RayBio Mouse Inflammation Antibody Array. Ultimately, histopathology and survival studies were conducted. The results showed that TMZ and DZ-conditioned medium significantly increasing the survival and improvement of histopathological score. We found that MG-132-conditioned medium failed to show significant outcomes. This study demonstrated that human MSC secretome has the potential to control inflammation.
全身炎症反应综合征是对损伤的一种复杂的病理生理和免疫反应。脓毒症是一种危及生命的疾病，当身体对感染的反应导致其自身组织和器官受损时就会发生。干细胞疗法是一种调节免疫反应的新方法。间充质干细胞（MSC）通过分泌细胞外基质和调节免疫反应来建立再生龛。如果优化分泌分子的产生，MSC 细胞外基质可以用于治疗应用。使用小分子进行药理学预处理可以增加移植后 MSC 的存活率。本研究旨在探讨用 MG-132、曲美他嗪（TMZ）和二氮嗪（DZ）预处理的人胚胎衍生间充质干细胞（hESC-MSCs）的细胞外基质对 LPS 刺激的小鼠模型中这些细胞免疫调节效率的影响。小鼠经腹腔注射 LPS，在 LPS 注射后 6 小时，用 1ml 30×细胞外基质对动物进行腹腔内给药。然后用自动分析仪测量血清生化参数水平，并用市售的 RayBio 小鼠炎症抗体阵列分析血清炎症细胞因子水平。最终进行了组织病理学和生存研究。结果表明，TMZ 和 DZ 条件培养基显著提高了存活率和改善了组织病理学评分。我们发现 MG-132 条件培养基未能显示出显著的结果。这项研究表明，人 MSC 细胞外基质具有控制炎症的潜力。
