scholarly journals TWIST1 controls cellular senescence and energy metabolism in mesenchymal stem cells

2021 ◽  
Vol 42 ◽  
pp. 401-414
Author(s):  
C Voskamp ◽  
◽  
LA Anderson ◽  
WJLM Koevoet ◽  
S Barnhoorn ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cellular Senescence ◽  
Extracellular Acidification ◽  
Cell Lineages ◽  
Knowing That ◽  
Control Mscs ◽  
Multiple Cell ◽  
Cellular Bioenergetics ◽  
Secretory Phenotype

Mesenchymal stem cells (MSCs) are promising cells for regenerative medicine therapies because they can differentiate towards multiple cell lineages. However, the occurrence of cellular senescence and the acquiring of the senescence-associated secretory phenotype (SASP) limit their clinical use. Since the transcription factor TWIST1 influences expansion of MSCs, its role in regulating cellular senescence was investigated. The present study demonstrated that silencing of TWIST1 in MSCs increased the occurrence of senescence, characterised by a SASP profile different from irradiation-induced senescent MSCs. Knowing that senescence alters cellular metabolism, cellular bioenergetics was monitored by using the Seahorse XF apparatus. Both TWIST1-silencing-induced and irradiation-induced senescent MSCs had a higher oxygen consumption rate compared to control MSCs, while TWIST1-silencing-induced senescent MSCs had a low extracellular acidification rate compared to irradiation-induced senescent MSCs. Overall, data indicated how TWIST1 regulation influenced senescence in MSCs and that TWIST1 silencing-induced senescence was characterised by a specific SASP profile and metabolic state.

scholarly journals TWIST1 controls cellular senescence and energy metabolism in mesenchymal stem cells

2020 ◽  
Author(s):  
Chantal Voskamp ◽  
Laura A. Anderson ◽  
Wendy J. L. M. Koevoet ◽  
Sander Barnhoorn ◽  
Pier G. Mastroberardino ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cellular Senescence ◽  
Human Mscs ◽  
Metabolic Evaluation ◽  
Specific Expression ◽  
Cell Lineages ◽  
Control Mscs ◽  
Multiple Cell ◽  
Secretory Phenotype

AbstractMesenchymal stem cells (MSC) are promising cells for regenerative medicine therapies, because they can differentiate towards multiple cell lineages. However, heterogeneity in differentiation capacity is one of the main drawbacks that limit their use clinically. Differences in the occurrence of cellular senescence and in the expression of the senescence associated secretory phenotype (SASP) in MSC populations contribute to their heterogeneity. Here, we show the involvement of TWIST1 expression in the regulation of MSC senescence, demonstrating that silencing of TWIST1 in MSCs increased the occurrence of senescence. These senescent MSCs had a SASP that was different from irradiation-induced senescent MSCs. In addition, metabolic evaluation performed by the Seahorse XF apparatus showed that both TWIST1 silencing-induced and irradiation-induced senescent MSCs had a higher oxygen consumption compared to control MSCs, while TWIST1 silencing-induced senescent MSCs had a low extracellular acidification rate compared to the irradiation-induced senescent MSCs. Overall, our data indicate how TWIST1 regulation influences senescence in human MSCs and that TWIST1 silencing-induced senescence is characterized by a specific expression of the SASP and the metabolic state.

scholarly journals Senescence-Associated Secretory Phenotype Suppression Mediated by Small-Sized Mesenchymal Stem Cells Delays Cellular Senescence through TLR2 and TLR5 Signaling

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 63
Author(s):  
Ji Hye Kwon ◽  
Miyeon Kim ◽  
Soyoun Um ◽  
Hyang Ju Lee ◽  
Yun Kyung Bae ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cellular Senescence ◽  
Small Cells ◽  
Critical Determinant ◽  
Senescent Phenotype ◽  
Toll Like Receptor 2 ◽  
Secretory Phenotype ◽  
Major Factors

In order to provide a sufficient number of cells for clinical use, mesenchymal stem cells (MSCs) must be cultured for long-term expansion, which inevitably triggers cellular senescence. Although the small size of MSCs is known as a critical determinant of their fate, the main regulators of stem cell senescence and the underlying signaling have not been addressed. Umbilical cord blood-derived MSCs (UCB-MSCs) were obtained using size-isolation methods and then cultured with control or small cells to investigate the major factors that modulate MSC senescence. Cytokine array data suggested that the secretion of interukin-8 (IL-8) or growth-regulated oncogene-alpha (GROa) by senescent cells was markedly inhibited during incubation of small cells along with suppression of cognate receptor (C-X-C motif chemokine receptor2, CXCR2) via blockade of the autocrine/paracrine positive loop. Moreover, signaling via toll-like receptor 2 (TLR2) and TLR5, both pattern recognition receptors, drove cellular senescence of MSCs, but was inhibited in small cells. The activation of TLRs (2 and 5) through ligand treatment induced a senescent phenotype in small cells. Collectively, our data suggest that small cell from UCB-MSCs exhibit delayed cellular senescence by inhibiting the process of TLR signaling-mediated senescence-associated secretory phenotype (SASP) activation.

scholarly journals MicroSAGE Analysis of 2,353 Expressed Genes in a Single Cell-Derived Colony of Undifferentiated Human Mesenchymal Stem Cells Reveals mRNAs of Multiple Cell Lineages

Stem Cells ◽  
2001 ◽  
Vol 19 (5) ◽  
pp. 408-418 ◽  
Author(s):  
Nicola Tremain ◽  
Jarmo Korkko ◽  
David Ibberson ◽  
Gene C. Kopen ◽  
Carla DiGirolamo ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Single Cell ◽  
Human Mesenchymal Stem Cells ◽  
Cell Lineages ◽  
Multiple Cell

scholarly journals Bovine tongue epithelium-derived cells: A new source of bovine mesenchymal stem cells

2020 ◽  
Vol 40 (4) ◽  
Author(s):  
Jienny Lee ◽  
Jeong Su Byeon ◽  
Na-Yeon Gu ◽  
Siu Lee ◽  
Se-A Lee ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Culture Conditions ◽  
Class I Mhc ◽  
Mhc I ◽  
Cell Lineages ◽  
Mhc Ii ◽  
Multiple Cell ◽  
Low Glucose

Abstract Mesenchymal stem cells (MSCs) possess the ability to differentiate into multiple cell lineages, and thus, confer great potential for use in regenerative medicine and biotechnology. In the present study, we attempted to isolate and characterize bovine tongue tissue epithelium-derived MSCs (boT-MSCs) and investigate the culture conditions required for long-term culturing of boT-MSCs. boT-MSCs were successfully isolated by the collagenase digestion method and their proliferative capacity was maintained for up to 20 or more passages. We observed a significant increase in the proliferation of boT-MSCs during the 20 consecutive passages under low-glucose Dulbecco’s modified Eagle’s medium culture condition among the three culture conditions. These boT-MSCs presented pluripotency markers (octamer-binding transcription factor 3/4 (Oct3/4) and sex determining region Y-box2 (Sox2)) and cell surface markers, which included CD13, CD29, CD44, CD73, CD90, CD105, CD166, and major histocompatibility complex (MHC) class I (MHC-I) but not CD11b, CD14, CD31, CD34, CD45, CD80, CD86, CD106, CD117, and MHC-II at third passage. Moreover, these boT-MSCs could differentiate into mesodermal (adipocyte, osteocyte, and chondrocyte) cell lineages. Thus, the present study suggests that the tongue of bovines could be used as a source of bovine MSCs.

Mesenchymal Stem Cells Differentiation: Mitochondria Matter in Osteogenesis or Adipogenesis Direction

2020 ◽  
Vol 15 (7) ◽  
pp. 602-606
Author(s):  
Kun Ji ◽  
Ling Ding ◽  
Xi Chen ◽  
Yun Dai ◽  
Fangfang Sun ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Therapeutic Potential ◽  
Mesodermal Cell ◽  
Cell Lineages ◽  
Current Review ◽  
Differentiation Factors ◽  
The Relationship ◽  
Msc Differentiation

Mesenchymal Stem Cells (MSCs) exhibit enormous therapeutic potential because of their indispensable regenerative, reparative, angiogenic, anti-apoptotic, and immunosuppressive properties. MSCs can best differentiate into mesodermal cell lineages, including osteoblasts, adipocytes, muscle cells, endothelial cells and chondrocytes. Specific differentiation of MSCs could be induced through limited conditions. In addition to the relevant differentiation factors, drastic changes also occur in the microenvironment to conduct it in an optimal manner for particular differentiation. Recent evidence suggests that the mitochondria participate in the regulating of direction and process of MSCs differentiation. Therefore, our current review focuses on how mitochondria participate in both osteogenesis and adipogenesis of MSC differentiation. Besides that, in our current review, we try to provide a further understanding of the relationship between the behavior of mitochondria and the direction of MSC differentiation, which could optimize current cellular culturing protocols for further facilitating tissue engineering by adjusting specific conditions of stem cells.

Hydrogen alleviates cellular senescence via regulation of ROS/p53/p21 pathway in bone marrow-derived mesenchymal stem cells in vivo

2018 ◽  
Vol 106 ◽  
pp. 1126-1134 ◽  
Author(s):  
Wenbo Zhang ◽  
Chao Huang ◽  
Aijun Sun ◽  
Liang Qiao ◽  
Xi Zhang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Cellular Senescence

scholarly journals Mouse Androgenetic Embryonic Stem Cells Differentiated to Multiple Cell Lineages in Three Embryonic Germ Layers In Vitro

2009 ◽  
Vol 55 (3) ◽  
pp. 283-292 ◽  
Author(s):  
Takeshi TERAMURA ◽  
Yuta ONODERA ◽  
Hideki MURAKAMI ◽  
Syunsuke ITO ◽  
Toshihiro MIHARA ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Germ Layers ◽  
Cell Lineages ◽  
Multiple Cell

MicroRNA-487a-3p Regulates the Senescence of Mesenchymal Stem Cells by Targeting Silencing Information Regulator-Associated Enzyme 1 (SIRT1)

2021 ◽  
Vol 11 (8) ◽  
pp. 1576-1581
Author(s):  
Yiwei Shen ◽  
Xue Li ◽  
Xiaoke Wu ◽  
Yi Li ◽  
Yiwei Shen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cellular Senescence ◽  
Control Group ◽  
Human Mscs ◽  
Galactosidase Activity ◽  
Activity Staining ◽  
Plasmid Transfection ◽  
Related Proteins ◽  
The Relationship

SIRT1 is known to be closely associated with cellular senescence, while the relationship between miR-487a-3p and SIRT1 and their role in mesenchymal stem cells (MSCs) remains unclear. MiRDB analysis showed SIRT1 is a target of miR-487a-3p. Here we investigated whether miR-487a-3p modulates senescence of mesenchymal stem cells by targeting SIRT1. The human MSCs (hMSCs) were divided into control group (NC group), miR-487a-3p Mimics group, pCMV-SIRT+miR-487a-3p Mimics group followed by analysis of miR-487a-3p expression by qPCR and protein level of SIRT1, P21 and P53 by western blot. Dual luciferin report assay verified the binding of miR-487a-3p to SIRT1 mRNA and β-galactosidase activity staining detected hMSCs senescence. miR-487a-3p level was significantly elevated after miR-487a-3p Mimics treatment (P <0.01) without difference between miR-487a-3p Mimics group and pCMV-SIRT1 group+miR-487a-3pMimics (P >0.05). miR-487a-3p mimics significantly decreased SIRT1 level (P < 0.01), which was reversed by pCMVSIRT1 plasmid transfection (P <0.05). Moreover, miR-487a-3p could bind SIRT1 mRNA 3′-UTR region. Further more, miR-487a-3p Mimics induced cellular senescence as displayed by increased β-galactosidase activity (P <0.01) and increased level of senescence-related proteins P21 and P53 (P < 0.01), which were all reversed by overexpression of SIRT1 (P < 0.05). In conclusion, miR-487a-3p reduced SIRT1 expression, thus promoting hMSCs senescence, while overexpression of SIRT1 could counteract the senescence of hMSCs induced by miR-487a-3p.

scholarly journals Patient Heterogeneity in Acute Myeloid Leukemia: Leukemic Cell Communication by Release of Soluble Mediators and Its Effects on Mesenchymal Stem Cells

Diseases ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 74
Author(s):  
Elise Aasebø ◽  
Annette K. Brenner ◽  
Maria Hernandez-Valladares ◽  
Even Birkeland ◽  
Olav Mjaavatten ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Extracellular Matrix ◽  
Acute Myeloid Leukemia ◽  
Mesenchymal Stem Cells ◽  
Conditioned Medium ◽  
Untreated Control ◽  
Myeloid Leukemia ◽  
Control Mscs ◽  
Acute Myeloid

Acute myeloid leukemia (AML) is an aggressive bone marrow malignancy, and non-leukemic stromal cells (including mesenchymal stem cells, MSCs) are involved in leukemogenesis and show AML-supporting effects. We investigated how constitutive extracellular mediator release by primary human AML cells alters proteomic profiles of normal bone marrow MSCs. An average of 6814 proteins (range 6493−6918 proteins) were quantified for 41 MSC cultures supplemented with AML-cell conditioned medium, whereas an average of 6715 proteins (range 6703−6722) were quantified for untreated control MSCs. The AML effect on global MSC proteomic profiles varied between patients. Hierarchical clustering analysis identified 10 patients (5/10 secondary AML) showing more extensive AML-effects on the MSC proteome, whereas the other 31 patients clustered together with the untreated control MSCs and showed less extensive AML-induced effects. These two patient subsets differed especially with regard to MSC levels of extracellular matrix and mitochondrial/metabolic regulatory proteins. Less than 10% of MSC proteins were significantly altered by the exposure to AML-conditioned media; 301 proteins could only be quantified after exposure to conditioned medium and 201 additional proteins were significantly altered compared with the levels in control samples (153 increased, 48 decreased). The AML-modulated MSC proteins formed several interacting networks mainly reflecting intracellular organellar structure/trafficking but also extracellular matrix/cytokine signaling, and a single small network reflecting altered DNA replication. Our results suggest that targeting of intracellular trafficking and/or intercellular communication is a possible therapeutic strategy in AML.

Sign in / Sign up

Export Citation Format

Share Document