Senescent cells secrete several molecules that help to prevent the progression of cancer. However, cancer cells can also misuse these secreted elements to survive and grow. Since the molecular and functional bases of these different elements remain poorly understood, we analyzed the effect of senescent mesenchymal stromal cell (MSC) secretome on the biology of ARH-77 myeloma cells. In addition to differentiating in mesodermal derivatives, MSCs have sustained interest among researchers by supporting hematopoiesis, contributing to tissue homeostasis, and modulating inflammatory response, all activities accomplished primarily by the secretion of cytokines and growth factors. Moreover, senescence profoundly affects the composition of MSC secretome. In this study, we induced MSC senescence by oxidative stress, DNA damage, and replicative exhaustion. While the first two are considered to induce acute senescence, extensive proliferation triggers replicative (i.e., chronic) senescence. We cultivated cancer cells in the presence of acute and chronic senescent MSC-conditioned media and evaluated their proliferation, DNA damage, apoptosis, and senescence. Our findings revealed that senescent secretomes induced apoptosis or senescence, if not both, to different extents. This anti-tumor activity became heavily impaired when secretomes were collected from senescent cells previously in contact (i.e., primed) with cancer cells. Our analysis of senescent MSC secretomes with LC-MS/MS followed by Gene Ontology classification further indicated that priming with cancer profoundly affected secretome composition by abrogating the production of pro-senescent and apoptotic factors. We thus showed for the first time that compared with cancer-primed MSCs, naïve senescent MSCs can exert different effects on tumor progression.
BACKGROUND: The heart is surrounded by a membrane called pericardium or pericardial cavity. OBJECTIVE: In this study, we investigated the pericardial fluid (PF) for coating polycaprolactone (PCL) scaffolds. PFS, which is a PF component, was used for coating material. In addition to using PFS for surface coating, MED and fetal bovine serum (FBS) were also used for comparison. METHODS: Pericardial fluid cells (PFSc) isolated from PF were cultured on coated PCL scaffolds for 1, 3 and 5 days. Cell viability was determined using 3-(4, 5-di-methylthiazol- 2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. RESULTS: The MTT assay results showed that the viability of cells on PCL scaffold coated with PFS increased over time (P < 0.005), and cell viability was significantly different between PCL scaffolds coated with PFS and non-coated PCL scaffolds. However, cell viability was significantly higher in the PCL scaffolds coated with PFS than non-coated and coated with FBS, MED and PCL scaffolds. Scanning electron microscopy (SEM) microscopy images and MTT assay indicated that PFSc are attached, proliferated, and spread on PCL scaffolds, especially on PCL scaffolds coated with PFS. CONCLUSIONS: These results suggest that PFS is a biocompatible material for surface modification of PCL scaffolds, which can be used as a suitable material for tissue engineering applications.
Tissue engineering applications are widely used to repair and regenerate damaged tissues and organs. A scaffold, which is an important component in tissue engineering, provides a 3D environment for cells. In this study, the usability of PF components for the production of an ideal scaffold was investigated. For this aim, pericardial fluid (PF) was harvested from the bovine heart, then its structure and components were characterized. The results of Raman spectroscopy analysis, histological staining, and scanning electron microscopy (SEM) shows that the pericardial fluid contains collagen type I and IV, elastin, fibrin, and glycosaminoglycan (GAG), which are native extracellular matrix (ECM) components. The results demonstrated that (i) PF contains native ECM proteins and GAG such as collagen types I, III, and IV, elastin, and fibrin. (ii) The PF is highly similar to the native ECM structure. (iii) PF can significantly contribute to many tissue engineering studies as a native ECM material to increase the biocompatibility of biomaterials and to several in vitro/in vivo cell culture studies. (iv) PF containing multiple ECM molecules, can be used alone or together with hyaluronic acid, poly(ethylene glycol) (PEG), alginate, chitosan, matrigel, and gelatin methacryloyl (GelMA) materials in bioprinting systems for eliminating the disadvantages of these materials.
Perikardiyal sıvı (PF) heterojen bir hücre topluluğuna sahiptir. Bu hücrelerden biri de mezenkimal kök hücre özelliği taşıyarak başka hücrelere farklılaşma potansiyeline sahip olan mesotelyal hücrelerdir. Bu hücrelerin sayısı doku hasarıyla birlikte artarak büyüme faktörleri (VEGF, FGF-2, PDGF, TGF-b) ve ekstrasellüler matriks (ECM) moleküllerini sentezleyerek doku/organda meydana gelen hasarın onarımında önemli bir yer tutmaktadır. Bu çalışmada mesotelyal hücrelerin hücre kültür ortamına FGF-2 (basic fibroblast growth factor)' nin eklenmesiyle mesotelyal hücrelerin vasküler doku oluşumuna etkisi incelenmiştir. Bu amaçla büyüme faktörü eklenmiş ve büyüme faktörü eklenmemiş olan kontrol grubu hücrelerinin birinci ve beşinci günlerdeki ışık mikroskobu görüntüleri kullanılarak analiz edilmiştir. Bu görüntüler ve görüntü histogramları kullanılarak Hjorth parametreleri olan mobilite, aktivite ve komplekslik özellikleri, çarpıklık, basıklık ve entropi değerleri kullanılarak istatistiksel olarak analiz edilmiştir. Birinci ve beşinci günlerde FGF-2 eklenen ve eklenmeyen kültürdeki hücrelerin görüntülerinden hesaplanan özniteliklerin gruplar arasındaki farklılığı değerlendirmek için istatistiksel analizi yapılmıştır. Elde edilen sonuçlara göre birinci günde iki grup arasında ve beşinci günde iki grup arasında bağımsız örneklem t testi ve Mann-Whitney U testi neticesinde anlamlı farklılıklar olduğu (p < 0.05) görülmüştür. Doku hasarının giderilmesi için gerekli olan ECM bileşenleri ve büyüme faktörlerini sentezleyebilen mezotelyal hücrelerin literatürde yaygın olarak kullanılan mezenkimal kök hücreye alternatif olarak kullanılabileceği bu ön çalışma ile ortaya konulmuştur.
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