scholarly journals Molecular Genetic Analysis of Human Endometrial Mesenchymal Stem Cells That Survived Sublethal Heat Shock

2017 ◽  
Vol 2017 ◽  
pp. 1-14 ◽  
Author(s):  
A. E. Vinogradov ◽  
M. A. Shilina ◽  
O. V. Anatskaya ◽  
L. L. Alekseenko ◽  
I. I. Fridlyanskaya ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Heat Shock ◽  
Replicative Senescence ◽  
Molecular Genetic ◽  
Interaction Network ◽  
Molecular Genetic Analysis ◽  
Molecular Karyotyping ◽  
Sequencing Data ◽  
Oncogenic Signaling

High temperature is a critical environmental and personal factor. Although heat shock is a well-studied biological phenomenon, hyperthermia response of stem cells is poorly understood. Previously, we demonstrated that sublethal heat shock induced premature senescence in human endometrial mesenchymal stem cells (eMSC). This study aimed to investigate the fate of eMSC-survived sublethal heat shock (SHS) with special emphasis on their genetic stability and possible malignant transformation using methods of classic and molecular karyotyping, next-generation sequencing, and transcriptome functional analysis. G-banding revealed random chromosome breakages and aneuploidy in the SHS-treated eMSC. Molecular karyotyping found no genomic imbalance in these cells. Gene module and protein interaction network analysis of mRNA sequencing data showed that compared to untreated cells, SHS-survived progeny revealed some difference in gene expression. However, no hallmarks of cancer were found. Our data identified downregulation of oncogenic signaling, upregulation of tumor-suppressing and prosenescence signaling, induction of mismatch, and excision DNA repair. The common feature of heated eMSC is the silence of MYC, AKT1/PKB oncogenes, and hTERT telomerase. Overall, our data indicate that despite genetic instability, SHS-survived eMSC do not undergo transformation. After long-term cultivation, these cells like their unheated counterparts enter replicative senescence and die.

scholarly journals Replicative Senescence of Mesenchymal Stem Cells: A Continuous and Organized Process

PLoS ONE ◽  
2008 ◽  
Vol 3 (5) ◽  
pp. e2213 ◽  
Author(s):  
Wolfgang Wagner ◽  
Patrick Horn ◽  
Mirco Castoldi ◽  
Anke Diehlmann ◽  
Simone Bork ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Replicative Senescence

scholarly journals Intrinsic Variability Present in Wharton’s Jelly Mesenchymal Stem Cells and T Cell Responses May Impact Cell Therapy

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Fernanda Vieira Paladino ◽  
Luiz Roberto Sardinha ◽  
Carla Azevedo Piccinato ◽  
Anna Carla Goldberg
Keyword(s):  
Stem Cells ◽  
Cell Proliferation ◽  
Mesenchymal Stem Cells ◽  
T Cell ◽  
Replicative Senescence ◽  
T Cell Response ◽  
Wharton’S Jelly ◽  
T Cell Proliferation ◽  
Intrinsic Variability ◽  
Wharton's Jelly

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.

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

2020 ◽  
Vol 11 (1) ◽  
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.

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