Adipogenic Differentiation of Mesenchymal Stem Cells Alters Their Immunomodulatory Properties in a Tissue-Specific Manner

Abstract

Chronic inflammation is associated with formation of ectopic fat deposits that might represent damage‐induced aberrant mesenchymal stem cell (MSC) differentiation. Such deposits are associated with increased levels of inflammatory infiltrate and poor prognosis. Here we tested the hypothesis that differentiation from MSC to adipocytes in inflamed tissue might contribute to chronicity through loss of immunomodulatory function. We assessed the effects of adipogenic differentiation of MSC isolated from bone marrow or adipose tissue on their capacity to regulate neutrophil recruitment by endothelial cells and compared the differentiated cells to primary adipocytes from adipose tissue. Bone marrow derived MSC were immunosuppressive, inhibiting neutrophil recruitment to TNFα‐treated endothelial cells (EC), but MSC‐derived adipocytes were no longer able to suppress neutrophil adhesion. Changes in IL‐6 and TGFβ1 signalling appeared critical for the loss of the immunosuppressive phenotype. In contrast, native stromal cells, adipocytes derived from them, and mature adipocytes from adipose tissue were all immunoprotective. Thus disruption of normal tissue stroma homeostasis, as occurs in chronic inflammatory diseases, might drive “abnormal” adipogenesis which adversely influences the behavior of MSC and contributes to pathogenic recruitment of leukocytes. Interestingly, stromal cells programmed in native fat tissue retain an immunoprotective phenotype. Stem Cells 2017;35:1636–1646

Weighted gene correlation network analysis reveals novel biomarkers associated with mesenchymal stromal cell differentiation in early phase

“…In order to screen for candidate genes that can serve as potential biomarkers or therapeutic targets, the Phase I samples, associated with the brown module, were compared with the control samples, which led to the identification of 119 DEGs related to OS differentiation and 148 DEGs that were associated with AD differentiation. The identified DEGs were then compared with the brown module, which led to the identification of 13 common genes, including BHLHE40, FOSB (Schneider et al, 2017), CSRNP1, HBEGF (Li et al, 2019a), CLCF1 (Nahle et al, 2019), SPRY2 (Schneider et al, 2017), IL6 (Munir et al, 2017), PTGS2 (Feigenson et al, 2017), SGK1, FOXQ1, LIF (Huat et al, 2014), SERPINE1 (Karbiener et al, 2011) and ZNF281. Of interest, the previously identified OS differentiation-related genes FOSB, SPRY2 and PTGS2 were upregulated, while HBEGF, CLCF1 and LIF were downregulated.…”

Behavior and biocompatibility of rabbit bone marrow mesenchymal stem cells with bacterial cellulose membrane

“…Alizarin Red staining showed a fairly characteristic reddish coloration, providing evidence of this potential. According to Munir et al (2017) , formation of lipid vacuoles in the cell cytoplasm and staining by Oil Red characterize the formation of adipocytes; during adipogenic differentiation, several independent vacuoles can be found, and fuse as they expand inside the cell. In this study, cell culture using specific media for differentiation into mesodermal (chondrogenic, osteogenic, or adipogenic) lineages demonstrated the multipotentiality of rabbit BM-MSCs.…”

The Specific Features of the Inflammatory Process Accompanying Ligation of the Femoral Vein in Experiment Under the Conditions of Stem Cell Therapy

“…В обеих группах животных с использованием клеточных технологий (ложнооперированные с вве дением ММСК без изменений кровотока и крысы после инъекции ММСК в проекции лигированной вены) по сравнению с группой с простым моделиро ванием острого локального препятствия венозному кровотоку менее выражена степень возрастания лей коцитарной, в частности нейтрофильной, инфиль трации и раньше происходит ее нормализация (3 нед против 4 нед соответственно). Это, скорее всего, обу словлено не только иммуномодуляторным (иммуно супрессивным) действием ММСК, но и их способно стью снижать активность воспалительных процессов [1,11,12]. Следует учитывать возможность привле чения макрофагов к месту концентрации введенных ММСК их детритом [15,16].…”

“…При этом снижается активность не толь ко иммунной воспалительной реакции [3,5,6], но и острого воспалительного процесса [7][8][9][10]. Необ ходимо обратить внимание на то, что МСК и их эк зосомы не только обладают иммуномодуляторным эффектом, но часто проявляют и иммуносупрессив ное действие [1,11,12].…”