scholarly journals Hybrid complexes of high and low molecular weight hyaluronan delay in vitro replicative senescence of mesenchymal stromal cells: a pilot study for future therapeutic application

Aging ◽  
2018 ◽  
Vol 10 (7) ◽  
pp. 1575-1585 ◽  
Author(s):  
Nicola Alessio ◽  
Antonietta Stellavato ◽  
Tiziana Squillaro ◽  
Stefania Del Gaudio ◽  
Giovanni Di Bernardo ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Pilot Study ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Replicative Senescence ◽  
Low Molecular Weight ◽  
Therapeutic Application ◽  
Hybrid Complexes

scholarly journals Low Molecular Weight Hyaluronan Induces an Inflammatory Response in Ovarian Stromal Cells and Impairs Gamete Development In Vitro

2020 ◽  
Vol 21 (3) ◽  
pp. 1036 ◽  
Author(s):  
Jennifer E. Rowley ◽  
Farners Amargant ◽  
Luhan T. Zhou ◽  
Anna Galligos ◽  
Leah E. Simon ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Inflammatory Response ◽  
Granulosa Cell ◽  
Stromal Cells ◽  
Cell Function ◽  
Ovarian Follicles ◽  
Low Molecular Weight ◽  
Reproductive Aging ◽  
Ovarian Stroma

The ovarian stroma, the microenvironment in which female gametes grow and mature, becomes inflamed and fibrotic with age. Hyaluronan is a major component of the ovarian extracellular matrix (ECM), and in other aging tissues, accumulation of low molecular weight (LMW) hyaluronan fragments can drive inflammation. Thus, we hypothesized that LMW hyaluronan fragments contribute to female reproductive aging by stimulating an inflammatory response in the ovarian stroma and impairing gamete quality. To test this hypothesis, isolated mouse ovarian stromal cells or secondary stage ovarian follicles were treated with physiologically relevant (10 or 100 μg/mL) concentrations of 200 kDa LMW hyaluronan. In ovarian stromal cells, acute LMW hyaluronan exposure, at both doses, resulted in the secretion of a predominantly type 2 (Th2) inflammatory cytokine profile as revealed by a cytokine antibody array of conditioned media. Additional qPCR analyses of ovarian stromal cells demonstrated a notable up-regulation of the eotaxin receptor Ccr3 and activation of genes involved in eosinophil recruitment through the IL5-CCR3 signaling pathway. These findings were consistent with an age-dependent increase in ovarian stromal expression of Ccl11, a major CCR3 ligand. When ovarian follicles were cultured in 10 or 100 μg/mL LMW hyaluronan for 12 days, gametes with compromised morphology and impaired meiotic competence were produced. In the 100 μg/mL condition, LMW hyaluronan induced premature meiotic resumption, ultimately leading to in vitro aging of the resulting eggs. Further, follicles cultured in this LMW hyaluronan concentration produced significantly less estradiol, suggesting compromised granulosa cell function. Taken together, these data demonstrate that bioactive LMW hyaluronan fragments may contribute to reproductive aging by driving an inflammatory stromal milieu, potentially through eosinophils, and by directly compromising gamete quality through impaired granulosa cell function.

The In Vitro and In Vivo Effects of a Low-Molecular-Weight Fucoidan on the Osteogenic Capacity of Human Adipose-Derived Stromal Cells

2014 ◽  
Vol 20 (1-2) ◽  
pp. 275-284 ◽  
Author(s):  
Jessica Pereira ◽  
Sophie Portron ◽  
Blandine Dizier ◽  
Claire Vinatier ◽  
Martial Masson ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Stromal Cells ◽  
Low Molecular Weight ◽  
Adipose Derived Stromal Cells ◽  
In Vivo Effects

Wound-healing potential of human umbilical cord blood–derived mesenchymal stromal cells in vitro—a pilot study

Cytotherapy ◽  
2015 ◽  
Vol 17 (11) ◽  
pp. 1506-1513 ◽  
Author(s):  
Hi-Jin You ◽  
Sik Namgoong ◽  
Seung-Kyu Han ◽  
Seong-Ho Jeong ◽  
Eun-Sang Dhong ◽  
...  
Keyword(s):  
Wound Healing ◽  
Pilot Study ◽  
Cord Blood ◽  
Umbilical Cord ◽  
Mesenchymal Stromal Cells ◽  
Umbilical Cord Blood ◽  
Stromal Cells ◽  
Human Umbilical Cord Blood ◽  
Human Umbilical Cord

scholarly journals Human adipose-derived mesenchymal stromal cells from face and abdomen undergo replicative senescence and loss of genetic integrity after long-term culture

2021 ◽  
Author(s):  
Priscilla B Delben ◽  
Helena D Zomer ◽  
Camila A Silva ◽  
Rogerio S Gomes ◽  
Fernanda R Melo ◽  
...  
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Replicative Senescence ◽  
Genetic Integrity ◽  
Cell Therapies ◽  
Long Term Culture ◽  
Morphological Alterations ◽  
Fat Depots

Body fat depots are heterogeneous concerning their embryonic origin, structure, exposure to environmental stressors, and availability. Thus, investigating adipose-derived mesenchymal stromal cells (ASCs) from different sources is essential to standardization for future therapies. In vitro amplification is also critical because it may predispose cell senescence and mutations, reducing regenerative properties and safety. Here, we evaluated long-term culture of human facial ASCs (fASCs) and abdominal ASCs (aASCs) and showed that both met the criteria for MSCs characterization, but presented differences in their immunophenotypic profile, and differentiation and clonogenic potentials. The abdominal tissue yielded more ASCs, but facial cells displayed fewer mitotic errors at higher passages. However, both cell types reduced clonal efficiency over time and entered replicative senescence around P12, as evaluated by progressive morphological alterations, reduced proliferative capacity, and SA-β-galactosidase expression. Loss of genetic integrity was detected by a higher proportion of cells showing nuclear alterations and γH2AX expression. Our findings indicate that the source of ASCs can substantially influence their phenotype and therefore should be carefully considered in future cell therapies, avoiding, however, long-term culture to ensure genetic stability.

scholarly journals Infrapatellar fat pad-derived mesenchymal stromal cells from osteoarthritis patients: In vitro genetic stability and replicative senescence

2016 ◽  
Vol 35 (5) ◽  
pp. 1029-1037 ◽  
Author(s):  
Simona Neri ◽  
Serena Guidotti ◽  
Nicoletta Libera Lilli ◽  
Luca Cattini ◽  
Erminia Mariani
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Genetic Stability ◽  
Replicative Senescence ◽  
Infrapatellar Fat Pad ◽  
Fat Pad

scholarly journals Proteomic and Biological Analysis of the Effects of Metformin Senomorphics on the Mesenchymal Stromal Cells

2021 ◽  
Vol 9 ◽  
Author(s):  
Mustafa Burak Acar ◽  
Şerife Ayaz-Güner ◽  
Zeynep Gunaydin ◽  
Musa Karakukcu ◽  
Gianfranco Peluso ◽  
...  
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Replicative Senescence ◽  
Protein Composition ◽  
Proteome Analysis ◽  
Secretory Activity ◽  
New Drugs ◽  
Ros Scavenging ◽  
Age Related

Senotherapeutics are new drugs that can modulate senescence phenomena within tissues and reduce the onset of age-related pathologies. Senotherapeutics are divided into senolytics and senomorphics. The senolytics selectively kill senescent cells, while the senomorphics delay or block the onset of senescence. Metformin has been used to treat diabetes for several decades. Recently, it has been proposed that metformin may have anti-aging properties as it prevents DNA damage and inflammation. We evaluated the senomorphic effect of 6 weeks of therapeutic metformin treatment on the biology of human adipose mesenchymal stromal cells (MSCs). The study was combined with a proteome analysis of changes occurring in MSCs’ intracellular and secretome protein composition in order to identify molecular pathways associated with the observed biological phenomena. The metformin reduced the replicative senescence and cell death phenomena associated with prolonged in vitro cultivation. The continuous metformin supplementation delayed and/or reduced the impairment of MSC functions as evidenced by the presence of three specific pathways in metformin-treated samples: 1) the alpha-adrenergic signaling, which contributes to regulation of MSCs physiological secretory activity, 2) the signaling pathway associated with MSCs detoxification activity, and 3) the aspartate degradation pathway for optimal energy production. The senomorphic function of metformin seemed related to its reactive oxygen species (ROS) scavenging activity. In metformin-treated samples, the CEBPA, TP53 and USF1 transcription factors appeared to be involved in the regulation of several factors (SOD1, SOD2, CAT, GLRX, GSTP1) blocking ROS.

Sign in / Sign up

Export Citation Format

Share Document