Polyurethane–polylactide-based material doped with resveratrol decreases senescence and oxidative stress of adipose-derived mesenchymal stromal stem cell (ASCs)

Śmieszek

Węgrzyn

et al. 2018

JCM

Endocrine disorders, including equine metabolic syndrome (EMS), are a serious issue in veterinary medicine and horse breeding. Furthermore, EMS was shown to affect the cytophysiological properties of adipose-derived stem cells, reducing their therapeutic potential. However, it was shown that those cells can be rejuvenated while using a combination of two chemicals: 5-azacytydine (AZA) and resveratrol (RES). In the present study, we decided to evaluate the immunomodulatory properties of AZA/RES-treated adipose-derived stem cells (ASC) isolated from EMS horses (ASCEMS). Thus, we co-cultured ASC with peripheral blood mononuclear cells (PBMC) and RAW264.7 macrophages. Most attention was placed on regulatory T lymphocytes (TREG), as well as the messenger RNA (mRNA) and protein levels of several cytokines (tumor necrosis factor α (TNF-α), interleukin (IL)-6, IL-10, and IL-1β). Moreover, we also investigated the expression of genes related to auto- and mitophagy in both PBMCs and ASCs. PBMCs were obtained from healthy and EMS-suffering individuals and were co-cultured with ASCs that were isolated from healthy and EMS horses cultured in control conditions and with AZA/RES. We discovered that cells treated with AZA/RES increase the TREG number while co-cultured with PBMCs. Moreover, the co-culture of PBMCs with AZA/RES-treated ASCEMS induced mitophagy in PBMCs. Furthermore, ASCEMS pre-treated with AZA/RES displayed anti-inflammatory properties, as decreased levels of TNF-α, nitric oxide (NO), and IL-6 were observed in those cells in comparison with their untreated counterparts in the co-culture with RAW264.7 macrophages. In summary, we demonstrated that ASCEMS treated with AZA/RES displayed increased anti-inflammatory properties, and was able to regulate and activate the TREG-related anti-inflammatory response.

Section: Introductionsupporting

confidence: 81%

Immunomodulatory Properties of Adipose-Derived Stem Cells Treated with 5-Azacytydine and Resveratrol on Peripheral Blood Mononuclear Cells and Macrophages in Metabolic Syndrome Animals

Śmieszek

Węgrzyn

et al. 2018

JCM

“…Lagouge et al has demonstrated that RES improves mitochondrial function and protects against metabolic disease by inducing PGC‐1α and SIRT1 activity. Our own data revealed that polyurethane/polylactide‐based material doped with RES decreased senescence and oxidative stress of ASCs. The fabricated material directed ASCs towards an osteoblast‐like phenotype, which indicated its potential application in regenerative medicine.…”

Section: Introductionmentioning

confidence: 69%

“…The effects of RES on cellular senescence have been widely investigated, although the results are contradictory. Multiple studies, including our own, have pointed out that RES can attenuate cell ageing; other have demonstrated that it can actually induce senescent phenotype, but in cancer cell lines . However, the molecular mechanisms responsible for that activity were not fully elucidated.…”

Section: Discussionmentioning

confidence: 95%

5‐Azacytydine and resveratrol reverse senescence and ageing of adipose stem cells via modulation of mitochondrial dynamics and autophagy

J Cellular Molecular Medi

Szłapka-Kosarzewska

Śmieszek

et al. 2018

Self Cite

Obesity and endocrine disorders have become prevalent issues in the field of both human and veterinary medicine. Equine metabolic syndrome is a complex disorder involving alternation in metabolism and chronic systemic inflammation. It has been shown that unfavourable microenvironment of inflamed adipose tissue negatively affects adipose stem cell population (ASC) residing within, markedly limiting their therapeutic potential. ASCsEMS are characterized by increased senescence apoptosis, excessive accumulation of reactive oxygen species (ROS), mitochondria deterioration and “autophagic flux.” The aim of the present study was to evaluate whether treatment of ASCsEMS with a combination of 5‐azacytydine (AZA) and resveratrol (RES) would reverse aged phenotype of these cells. For this reason, we performed the following analyzes: molecular biology (RT‐PCR), microscopic (immunofluorescence, TEM) and flow cytometry (JC‐1, ROS, Ki67). We evaluated the mitochondrial status, dynamics and clearance as well as autophagic pathways. Furthermore, we investigated epigenetic alternations in treated cells by measuring the expression of TET genes and analysis of DNA methylation status. We have demonstrated that AZA/RES treatment of ASCsEMS is able to rejuvenate these cells by modulating mitochondrial dynamics, in particular by promoting mitochondrial fusion over fission. After AZA/RES treatment, ASCsEMS were characterized by increased proliferation rate, decreased apoptosis and senescence and lower ROS accumulation. Our findings offer a novel approach and potential targets for the beneficial effects of AZA/RES in ameliorating stem cell dysfunctions.

“…One of the most effective substance in attenuation of stem cell senescence is resveratrol (RES). It was shown to decrease oxidative stress, reduce apoptosis, enhance proliferation and paracrine activity of MSC [ 12 , 81 ]. It was also proved, that sirtuin 1 overexpression delays senescence in MSCs that have undergone prolonged culturing and sustain their adipogenic and osteogenic potential [ 82 ].…”

Section: Rejuvenation Of Deteriorated Cells In Vitromentioning

confidence: 99%

Dysfunction of Mesenchymal Stem Cells Isolated from Metabolic Syndrome and Type 2 Diabetic Patients as Result of Oxidative Stress and Autophagy may Limit Their Potential Therapeutic Use

Houston²,

Marycz

2018

Stem Cell Rev and Rep

145

112

Mesenchymal stem cells (MSC) have become a promising tool for therapeutic intervention. Their unique features, including self-renewal, multipotency and immunomodulatory properties draw the worldwide attention of researchers and physicians with respect to their application in disease treatment. However, the environment (so-called niche) from which MSCs are isolated may determine their usefulness. Many studies indicated the involvement of MSCs in ageing and disease. In this review, we have focused on how type 2 diabetes (T2D) and metabolic syndrome (MS) affect MSC properties, and thus limit their therapeutic potential. Herein, we mainly focus on apoptosis, autophagy and mitochondria deterioration processes that indirectly affect MSC fate. Based on the data presented, special attention should be paid when considering autologous MSC therapy in T2D or MS treatments, as their therapeutic potential may be restricted.