Laboratory of Experimental Haematology, Department of Clinical and Toxicological Analysis, School of Pharmaceutical Sciences, University of São Paulo, Avenida Lineu Prestes, 580-Bloco 17, São Paulo, SP, 05508-900, Brazil.
Eur J Nutr. 2022 Oct;61(7):3391-3406. doi: 10.1007/s00394-022-02893-0. Epub 2022 May 5.
Dietary protein deficiency is common in the elderly, compromising hematopoiesis and the immune response, and may cause a greater susceptibility to infections. Mesenchymal stem cells (MSCs) have immunomodulatory properties and are essential to hematopoiesis. Therefore, this study aimed to investigate, in an aging model subjected to malnutrition due a reduced protein intake, aspects related to the immunomodulatory capacity of MSCs.
Male C57BL/6 mice from young and elderly groups were fed with normoproteic or hypoproteic diets (12% and 2% of protein, respectively) and nutritional, biochemical and hematological parameters were evaluated. MSCs from bone marrow were isolated, characterized and their secretory parameters evaluated, along with gene expression. Additionally, the effects of aging and protein malnutrition on MSC immunomodulatory properties were assessed.
Malnourished mice lost weight and demonstrated anemia, leukopenia, and bone marrow hypoplasia. MSCs from elderly animals from both groups showed reduced CD73 expression and higher senescence rate; also, the malnourished state affected CD73 expression in young animals. The production of IL-1β and IL-6 by MSCs was affected by aging and malnutrition, but the IL-10 production not. Aging also increased the expression of NFκB, reducing the expression of STAT-3. However, MSCs from malnourished groups, regardless of age, showed decreased TGF-β and PGE production. Evaluation of the immunomodulatory capacity of MSCs revealed that aging and malnutrition affected, mainly in lymphocytes, the production of IFN-γ and IL-10.
Aging and reduced protein intake are factors that, alone or together, influence the immunomodulatory properties of MSCs and provide basic knowledge that can be further investigated to explore whether MSCs' therapeutic potential may be affected.
老年人中普遍存在蛋白质缺乏症，这会损害造血功能和免疫反应，并可能导致更高的感染易感性。间充质干细胞（MSCs）具有免疫调节特性，对造血至关重要。因此，本研究旨在研究由于蛋白质摄入减少而导致营养不良的衰老模型中，与 MSCs 的免疫调节能力相关的方面。
年轻和老年组的雄性 C57BL/6 小鼠分别喂食高蛋白或低蛋白饮食（分别为 12%和 2%的蛋白质），并评估营养、生化和血液学参数。从骨髓中分离、鉴定 MSC，并评估其分泌参数和基因表达。此外，还评估了衰老和蛋白质营养不良对 MSC 免疫调节特性的影响。
营养不良的小鼠体重减轻，表现出贫血、白细胞减少和骨髓发育不全。来自两组老年动物的 MSC 表达 CD73 的能力降低，衰老速度加快；此外，营养不良状态也影响了年轻动物的 CD73 表达。MSC 产生的 IL-1β 和 IL-6 受衰老和营养不良的影响，但 IL-10 的产生不受影响。衰老还增加了 NFκB 的表达，降低了 STAT-3 的表达。然而，无论年龄大小，来自营养不良组的 MSC 产生 TGF-β 和 PGE 的能力降低。对 MSC 免疫调节能力的评估表明，衰老和低蛋白摄入单独或共同影响了 MSC 的免疫调节特性，并提供了基本的知识，可以进一步研究以探讨 MSCs 的治疗潜力是否受到影响。
