Study on the Dynamic Biological Characteristics of Human Bone Marrow Mesenchymal Stem Cell Senescence

Abstract

Objective. To preliminary explore the senescent dynamic changes of the bone marrow mesenchymal stem cells (BMMSCs) by human ageing and its possible mechanism. Methods. The bone marrows were harvested from healthy volunteers, and according to volunteers’ age, these were divided into group A (≤25 years), group B (26-45 years), group C (46-65 years), and group D (>65 years). Totally, the bone marrows were extracted from the posterior superior iliac spine from volunteers under aseptic conditions. Diluted with isovolumic PBS, followed by centrifugation at 1×105/cm2, cells were cultured in a 5% CO2 incubator at 37°C. After three passages, surface marker identification of hBMMSCs was tested by flow cytometry (FCM), oil red O staining was used to observe the ability of osteogenic differentiation, alkaline phosphatase (ALP) staining and the levels of osteocalcin (OST) in the supernatants were used to observe the ability of adipogenic differentiation, senescence-associated β-galactosidase (SA-β-Gal) staining was used to detect the senescent BMSCs, the ability of BMSC proliferation was detected by cell counting kit-8 (CCK-8), the distribution of the cell cycle was analyzed by flow cytometry (FCM), and malondialdehyde (MDA) content, total glutathione peroxidase, total antioxidant capacity, and total superoxide dismutase (SOD) activity was analyzed using enzymatic assay. Results. The BMSCs highly expressed CD73 and CD90, but lowly expressed CD34 and CD19/CD14. With age, osteogenic differentiation was markedly increased and audiogenic differentiation was significantly decreased. The number of SA-β-gal-positive cells was significantly increased, the proliferation ability of hBMMSCs declined, the BMSCs were held in the G1 phase, the MDA level of BMSCs was significantly increased, and total glutathione peroxidase, total antioxidant capacity, and SOD activity significantly declined. Conclusions. With age, the aging BMSCs were intensified; the mechanism may be related to oxidative damage mediated aging-related pathways.

Antioxidant Effect of Beer Polyphenols and Their Bioavailability in Dental-Derived Stem Cells (D-dSCs) and Human Intestinal Epithelial Lines (Caco-2) Cells

“…The ROS/RNS produced by several endogenous and exogenous processes is neutralized by cellular antioxidant defenses. Imbalance between ROS/RNS and the antioxidant defenses results in cellular oxidative stress [ 3 , 25 ]. This imbalance occurs in the case of aging and leads to progressive loss of tissue and organ function.…”

“…This imbalance occurs in the case of aging and leads to progressive loss of tissue and organ function. Stem cell senescence and functional decline have emerged among the core features of aging, underlying deficient regenerative potential, and lost tissue homeostasis in various organs/systems [ 25 , 28 ]. Natural compounds are commonly used for the prevention of various senescence changes, such as antioxidants and anti-inflammatory agents [ 23 ].…”

“…Senescence has a dualistic function: from one side, it protects cells from damage and oncogene activation but on the other, it limits the possibility for tissue regeneration triggering aging-related deterioration. In a sense, senescence is the recapitulation, in the cell, of aging in an organism [ 25 ]. In the last decades, the use of synthetic and natural molecules has contributed to the development of strategies that may counteract stem cell senescence allowing for the preservation of tissue homeostasis and our innate self-healing potential.…”

“…Mesenchymal stem cells (MSCs), adult stem cells with the potential of differentiation into different lineages, play an important role in tissue homeostasis and regeneration [ 26 , 27 ]. Data show that ROS increase in aged MSCs, and accumulated oxidative damage leads to abnormal proliferation and ultimately MSC senescence [ 25 , 28 ].…”

Hedgehog pathway inhibition causes primary follicle atresia and decreases female germline stem cell proliferation capacity or stemness

“…Glutathione (GSH) is an important tripeptide that protects the cell against the noxious effects of oxidative material [28]. Malondialdehyde (MDA), a representative lipid peroxide, is generated in cells when oxygen radical levels increase [29]. The activity of SOD2 and GPx, as well as the concentration of GSH and MDA, was used to measure the oxidative stress level in this study [30,31].…”