Department of Anatomy, Faculty of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia.
Department of Anatomy, Faculty of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia; Benha University, Faculty of Medicine, Histology & Cell Biology Department, Egypt.
Transpl Immunol. 2022 Jun;72:101586. doi: 10.1016/j.trim.2022.101586. Epub 2022 Mar 29.
Cardio-renal syndrome (CRS) denotes the convergence of heart-kidney interactions across several mechanisms. The current study is conducted to evaluate the anti-inflammatory role of adipose tissue-derived stem cells (ASCs) versus adipose stem cell-derived extracellular vesicles (ADSCs-EVs) in experimental model of cardiorenal syndrome type III. The study was conducted on 50 male rats that were equally divided to: group I (control group); Group II (experimental cardiorenal syndrome group) which induced by right renal artery ligation (ICRSIII); Group III (Sham-operated control group) which underwent surgical incision without renal artery ligation; Group IV (ICRSIII which received ADSCs-extracellular vesicles (ADSCs-EVs); Group V (ICRSIII which received adipose tissue stem cells (ASCs). Assessment of pro-inflammatory cytokines; IL-10, IL-1α, IL-6, IL-1 β, IFN-γ, NF-α and their mRNA gene expression quantitation, (NGAL), and brain natriuretic peptide (BNP) as markers of cardiac dysfunction, as well as histopathological examination of renal tissue was examined by H& E, Masson trichrome and periodic acid-Schiff stains (PAS). The ICRS group exhibited significant acute tubular injury with tubular dilation, loss of brush borders, epithelial flattening, and occasional sloughed cells in lumen. Use of either ADSCs-EVs or ASCs significantly ameliorated the histological findings of tubular injury. Proinflammatory cytokines, BNP and NGAL were significantly elevated in ICRSIII group as compared to all other studied groups. Administration of ADSCs-EVs or ASCs led to significant decrease in all proinflammatory cytokines as well as BNP and NGAL levels with no significant difference between them. In conclusion, ADSCs-EXs and ASCs exhibited significant repairing effects in experimental-induced cardiorenal syndrome type III as evidenced by amelioration of histological findings of tubular injury, anti-inflammatory effects, and the significant decrease in markers of cardiac dysfunction. ADSC-EVs reprogramed injured cardiac cells by activating regenerative processes.
心肾综合征（CRS）表示几种机制下心脏与肾脏相互作用的汇聚。本研究旨在评估脂肪组织源性干细胞（ASCs）与脂肪干细胞衍生的细胞外囊泡（ADSCs-EVs）在 III 型心肾综合征实验模型中的抗炎作用。该研究共纳入 50 只雄性大鼠，平均分为 5 组：I 组（对照组）；II 组（实验性心肾综合征组），通过右肾动脉结扎诱导；III 组（假手术对照组），仅进行手术切口而不结扎肾动脉；IV 组（接受 ADSCs-EVs 治疗的 ICRSIII 组）；V 组（接受脂肪组织干细胞（ASCs）治疗的 ICRSIII 组）。评估促炎细胞因子；IL-10、IL-1α、IL-6、IL-1β、IFN-γ、NF-α 及其 mRNA 基因表达定量、（NGAL）和脑利钠肽（BNP）作为心脏功能障碍的标志物，以及肾组织的组织病理学检查通过 H&E、Masson 三色和过碘酸-Schiff 染色（PAS）进行。ICRS 组表现出明显的急性肾小管损伤，表现为管腔扩张、刷状缘丢失、上皮扁平以及偶尔腔内脱落细胞。使用 ADSCs-EVs 或 ASCs 可显著改善肾小管损伤的组织学发现。与所有其他研究组相比，ICRSIII 组的促炎细胞因子、BNP 和 NGAL 水平显著升高。给予 ADSCs-EVs 或 ASCs 可显著降低所有促炎细胞因子以及 BNP 和 NGAL 水平，两者之间无显著差异。总之，ADSCs-EXs 和 ASCs 在实验诱导的 III 型心肾综合征中表现出显著的修复作用，表现在肾小管损伤的组织学发现改善、抗炎作用以及心脏功能障碍标志物的显著降低。ADSC-EVs 通过激活再生过程来重编程受损的心脏细胞。
