Tracking of Replicative Senescence in Mesenchymal Stem Cells by Colony-Forming Unit Frequency

Wharton’s jelly mesenchymal stem cells (WJ-MSC) exhibit immunomodulatory effects on T cell response. WJ-MSC are easy to collect, process, and proliferate rapidly in culture, but information on the variability of individual cell samples impacting upon in vitro expansion, immunomodulatory potential, and aging processes is still lacking. We propose to evaluate the immunomodulatory cytokine profile and capacity to inhibit T cell proliferation of WJ-MSC progressing to replicative senescence in order to analyze if expected responses are affected. Our results show that the gene expression of immunomodulatory molecules varied among samples with no specific pattern present. In coculture, all WJ-MSC were capable of inhibiting mitogen-activated CD3+ T cell proliferation, although to different degrees, and each PBMC responded with a different level of inhibition. Thus, we suggest that each WJ-MSC displays unique behavior, differing in patterns of cytokine mRNA expression and immunomodulatory capacity. We believe that variability between samples may play a role in the effectiveness of WJ-MSC employed therapeutically.

Download Full-text

Alteration of fatty acid oxidation by increased CPT1A on replicative senescence of placenta-derived mesenchymal stem cells

Stem Cell Research & Therapy ◽

10.1186/s13287-019-1471-y ◽

2020 ◽

Vol 11 (1) ◽

Cited By ~ 15

Author(s):

Jin Seok ◽

Hyun Sook Jung ◽

Sohae Park ◽

Jung Ok Lee ◽

Chong Jai Kim ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Fatty Acid ◽

Mitochondrial Dysfunction ◽

Fatty Acid Oxidation ◽

Replicative Senescence ◽

Acid Oxidation ◽

Differentiation Potential ◽

Passage Number

Abstract Background Human placenta-derived mesenchymal stem cells (PD-MSCs) are powerful sources for cell therapy in regenerative medicine. However, a limited lifespan by senescence through mechanisms that are well unknown is the greatest obstacle. In the present study, we first demonstrated the characterization of replicative senescent PD-MSCs and their possible mitochondrial functional alterations. Methods Human PD-MSCs were cultured to senescent cells for a long period of time. The cells of before passage number 8 were early cells and after passage number 14 were late cells. Also, immortalized cells of PD-MSCs (overexpressed hTERT gene into PD-MSCs) after passage number 14 were positive control of non-senescent cells. The characterization and mitochondria analysis of PD-MSCs were explored with long-term cultivation. Results Long-term cultivation of PD-MSCs exhibited increases of senescent markers such as SA-β-gal and p21 including apoptotic factor, and decreases of proliferation, differentiation potential, and survival factor. Mitochondrial dysfunction was also observed in membrane potential and metabolic flexibility with enlarged mitochondrial mass. Interestingly, we founded that fatty acid oxidation (FAO) is an important metabolism in PD-MSCs, and carnitine palmitoyltransferase1A (CPT1A) overexpressed in senescent PD-MSCs. The inhibition of CPT1A induced a change of energy metabolism and reversed senescence of PD-MSCs. Conclusions These findings suggest that alteration of FAO by increased CPT1A plays an important role in mitochondrial dysfunction and senescence of PD-MSCs during long-term cultivation.

Download Full-text

Cell Contact Accelerates Replicative Senescence of Human Mesenchymal Stem Cells Independent of Telomere Shortening and p53 Activation: Roles of Ras and Oxidative Stress

Cell Transplantation ◽

10.3727/0963689109x546562 ◽

2011 ◽

Vol 20 (8) ◽

pp. 1209-1220 ◽

Cited By ~ 11

Author(s):

Jennifer H. Ho ◽

Yu-Fan Chen ◽

Wei-Hsien Ma ◽

Tzu-Ching Tseng ◽

Ming-Hsiang Chen ◽

...

Keyword(s):

Oxidative Stress ◽

Stem Cells ◽

Mesenchymal Stem Cells ◽

Replicative Senescence ◽

Human Mesenchymal Stem Cells ◽

Cell Contact ◽

Telomere Shortening ◽

P53 Activation ◽

And Oxidative Stress

Download Full-text

Matrix elasticity, replicative senescence and DNA methylation patterns of mesenchymal stem cells

Biomaterials ◽

10.1016/j.biomaterials.2014.04.079 ◽

2014 ◽

Vol 35 (24) ◽

pp. 6351-6358 ◽

Cited By ~ 39

Author(s):

Anne Schellenberg ◽

Sylvia Joussen ◽

Kristin Moser ◽

Nico Hampe ◽

Nils Hersch ◽

...

Keyword(s):

Dna Methylation ◽

Stem Cells ◽

Mesenchymal Stem Cells ◽

Replicative Senescence ◽

Matrix Elasticity ◽

Methylation Patterns

Download Full-text

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

PeerJ ◽

10.7717/peerj.4656 ◽

2018 ◽

Vol 6 ◽

pp. e4656 ◽

Cited By ~ 7

Author(s):

Marcello de Alencar Silva ◽

Yulla Klinger de Carvalho Leite ◽

Camila Ernanda Sousa de Carvalho ◽

Matheus Levi Tajra Feitosa ◽

Michel Muálem de Moraes Alves ◽

...

Keyword(s):

Nitric Oxide ◽

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Macrophage Activation ◽

Cellulose Membrane ◽

Colony Forming Unit ◽

Bacterial Cellulose Membrane ◽

Marrow Mesenchymal Stem Cells ◽

Rabbit Bone

Background Tissue engineering has been shown to exhibit great potential for the creation of biomaterials capable of developing into functional tissues. Cellular expansion and integration depends on the quality and surface-determinant factors of the scaffold, which are required for successful biological implants. The objective of this research was to characterize and evaluate the in vitro characteristics of rabbit bone marrow mesenchymal stem cells (BM-MSCs) associated with a bacterial cellulose membrane (BCM). We assessed the adhesion, expansion, and integration of the biomaterial as well as its ability to induce macrophage activation. Finally, we evaluated the cytotoxicity and toxicity of the BCM. Methods Samples of rabbit bone marrow were collected. Mesenchymal stem cells were isolated from medullary aspirates to establish fibroblast colony-forming unit assay. Osteogenic, chondrogenic, and adipogenic differentiation was performed. Integration with the BCM was assessed by scanning electron microscopy at 1, 7, and 14 days. Cytotoxicity was assessed via the production of nitric oxide, and BCM toxicity was assessed with the MTT assay; phagocytic activity was also determined. Results The fibroblastoid colony-forming unit (CFU-F) assay showed cells with a fibroblastoid morphology organized into colonies, and distributed across the culture area surface. In the growth curve, two distinct phases, lag and log phase, were observed at 15 days. Multipotentiality of the cells was evident after induction of osteogenic, chondrogenic, and adipogenic lineages. Regarding the BM-MSCs’ bioelectrical integration with the BCM, BM-MSCs were anchored in the BCM in the first 24 h. On day 7 of culture, the cytoplasm was scattered, and on day 14, the cells were fully integrated with the biomaterial. We also observed significant macrophage activation; analysis of the MTT assay and the concentration of nitric oxide revealed no cytotoxicity of the biomaterial. Conclusion The BCM allowed the expansion and biointegration of bone marrow progenitor cells with a stable cytotoxic profile, thus presenting itself as a biomaterial with potential for tissue engineering.

Download Full-text

Replicative senescence of mesenchymal stem cells causes DNA-methylation changes which correlate with repressive histone marks

Aging ◽

10.18632/aging.100391 ◽

2011 ◽

Vol 3 (9) ◽

pp. 873-888 ◽

Cited By ~ 103

Author(s):

Anne Schellenberg ◽

Qiong Lin ◽

Herdit Schüler ◽

Carmen M. Koch ◽

Sylvia Joussen ◽

...

Keyword(s):

Dna Methylation ◽

Stem Cells ◽

Mesenchymal Stem Cells ◽

Replicative Senescence ◽

Histone Marks

Download Full-text

Senescent Mesenchymal Stem Cells in Myelodysplastic Syndrome: Functional Alterations, Molecular Mechanisms, and Therapeutic Strategies

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2020.617466 ◽

2021 ◽

Vol 8 ◽

Author(s):

Xiaofang Chen ◽

Ningyu Li ◽

Jianyu Weng ◽

Xin Du

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Myelodysplastic Syndrome ◽

Molecular Mechanisms ◽

Replicative Senescence ◽

Bone Marrow Microenvironment ◽

Hematopoietic Stem ◽

Hematopoietic Disorders ◽

Cellular Components

Myelodysplastic syndrome (MDS) is a group of clonal hematopoietic disorders related to hematopoietic stem and progenitor cell dysfunction. However, therapies that are currently used to target hematopoietic stem cells are not effective. These therapies are able to slow the evolution toward acute myeloid leukemia but cannot eradicate the disease. Mesenchymal stem cells (MSCs) have been identified as one of the main cellular components of the bone marrow microenvironment, which plays an indispensable role in normal hematopoiesis. When functional and regenerative capacities of aging MSCs are diminished, some enter replicative senescence, which promotes inflammation and disease progression. Recent studies that investigated the contribution of bone marrow microenvironment and MSCs to the initiation and progression of the disease have offered new insights into the MDS. This review presents the latest updates on the role of MSCs in the MDS and discusses potential targets for the treatment of MDS.

Download Full-text

Glucose-Induced Replicative Senescence in Mesenchymal Stem Cells

Rejuvenation Research ◽

10.1089/rej.2006.9.31 ◽

2006 ◽

Vol 9 (1) ◽

pp. 31-35 ◽

Cited By ~ 90

Author(s):

Alexandra Stolzing ◽

Natalie Coleman ◽

Andrew Scutt

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Replicative Senescence

Download Full-text