Cobalt Chloride Enhances the Stemness of Human Dental Pulp Cells

Laksana, Kantaporn; Sooampon, Sireerat; Pavasant, Prasit; Sriarj, Wannakorn

doi:10.1016/j.joen.2017.01.005

Cited by 23 publications

(19 citation statements)

References 35 publications

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“…Therefore, CoCl 2 successfully mimicked the hypoxic condition in DPMSCs and UCMSCs but failed in inducing hypoxic microenviroment in ADMSCs. Our data are in agreement with previous results on murine bone marrow mesenchymal stem cells [ 21 ], human periodontal ligament MSCs [ 26 ], and DPMSCs [ 25 ] where the hypoxic induction by CoCl 2 triggered the HIF-1 α pathway.…”

Section: Discussionsupporting

confidence: 93%

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The Hypoxia-Mimetic Agent Cobalt Chloride Differently Affects Human Mesenchymal Stem Cells in Their Chondrogenic Potential

Teti

Focaroli

Salvatore

et al. 2018

Stem Cells International

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Adult stem cells are a promising cell source for cartilage regeneration. They resided in a special microenvironment known as the stem-cell niche, characterized by the presence of low oxygen concentration. Cobalt chloride (CoCl2) imitates hypoxia in vitro by stabilizing hypoxia-inducible factor-alpha (HIF-1α), which is the master regulator in the cellular adaptive response to hypoxia. In this study, the influence of CoCl2 on the chondrogenic potential of human MSCs, isolated from dental pulp, umbilical cord, and adipose tissue, was investigated. Cells were treated with concentrations of CoCl2 ranging from 50 to 400 μM. Cell viability, HIF-1α protein synthesis, and the expression of the chondrogenic markers were analyzed. The results showed that the CoCl2 supplementation had no effect on cell viability, while the upregulation of chondrogenic markers such as SOX9, COL2A1, VCAN, and ACAN was dependent on the cellular source. This study shows that hypoxia, induced by CoCl2 treatment, can differently influence the behavior of MSCs, isolated from different sources, in their chondrogenic potential. These findings should be taken into consideration in the treatment of cartilage repair and regeneration based on stem cell therapies.

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Section: Discussionsupporting

confidence: 93%

“…Cobalt chloride, a chemical hypoxia-mimetic agent, is an attractive alternative to creating physical hypoxic agents [ 25 – 27 ]. The potential toxicity of CoCl 2 on the different MSCs utilized in this study was investigated by MTT analysis.…”

Section: Discussionmentioning

confidence: 99%

The Hypoxia-Mimetic Agent Cobalt Chloride Differently Affects Human Mesenchymal Stem Cells in Their Chondrogenic Potential

Teti

Focaroli

Salvatore

et al. 2018

Stem Cells International

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“…Oxygen saturation level is one major factor determining biological activities of stem cells. Hypoxia promotes cell growth and migration, and it helps maintain cell stemness [8,9]. The effects of hypoxia are primarily mediated by hypoxia-inducible factors (HIFs) [10], which are DNA-binding transcriptional factors and bind to hypoxia-regulated elements (HREs) in the promoter and enhancer of target genes [10].…”

Section: Introductionmentioning

confidence: 99%

“…A hypoxia state can be achieved and maintained by utilizing hypoxic chambers; however, changes of gas media (95% N 2 and 5% CO 2 ) for long-term cell culture are cost-and time-consuming. Therefore, hypoxia-mimicking agents such as cobalt chloride (CoCl 2 ) and deferoxamine (DFO) have been tried in the expansion of stem cells [12]; however, the cytotoxicity of this agent is still an issue [8]. In a hypoxic state, cell metabolism shifts from oxidative phosphorylation (OxPhos) to glycolysis for generation of adenosine triphosphate (ATP) and metabolic intermediates [13].…”

Section: Introductionmentioning

confidence: 99%

Succinate Supplement Elicited “Pseudohypoxia” Condition to Promote Proliferation, Migration, and Osteogenesis of Periodontal Ligament Cells

Mao

Yang

Zhao

et al. 2020

Stem Cells International

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Most mesenchymal stem cells reside in a niche of low oxygen tension. Iron-chelating agents such as CoCl2 and deferoxamine have been utilized to mimic hypoxia and promote cell growth. The purpose of the present study was to explore whether a supplement of succinate, a natural metabolite of the tricarboxylic acid (TCA) cycle, can mimic hypoxia condition to promote human periodontal ligament cells (hPDLCs). Culturing hPDLCs in hypoxia condition promoted cell proliferation, migration, and osteogenic differentiation; moreover, hypoxia shifted cell metabolism from oxidative phosphorylation to glycolysis with accumulation of succinate in the cytosol and its release into culture supernatants. The succinate supplement enhanced hPDLC proliferation, migration, and osteogenesis with decreased succinate dehydrogenase (SDH) expression and activity, as well as increased hexokinase 2 (HK2) and 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3), suggesting metabolic reprogramming from oxidative phosphorylation to glycolysis in a normal oxygen condition. The succinate supplement in cell cultures promoted intracellular succinate accumulation while stabilizing hypoxia inducible factor-1α (HIF-1α), leading to a state of pseudohypoxia. Moreover, we demonstrate that hypoxia-induced proliferation was G-protein-coupled receptor 91- (GPR91-) dependent, while exogenous succinate-elicited proliferation involved the GPR91-dependent and GPR91-independent pathway. In conclusion, the succinate supplement altered cell metabolism in hPDLCs, induced a pseudohypoxia condition, and enhanced proliferation, migration, and osteogenesis of mesenchymal stem cells in vitro.

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“…CoCl 2 , a widely used hypoxia-mimicking agent in vivo and in vitro, mimics hypoxia by preventing the degradation of HIF-1α (Ji et al 2006). Previous studies found that CoCl 2 increased stem cell marker mRNA expression and inhibited osteogenic differentiation in two less primitive dental-derived cells, i.e., human dental pulp cells (hDPCs) (Laksana et al 2017) and human periodontal ligament cells (hPDLCs) (Osathanon et al 2015).…”

Section: Introductionmentioning

confidence: 99%

Effects of cobalt chloride on the stem cell marker expression and osteogenic differentiation of stem cells from human exfoliated deciduous teeth

Chen

Zhao

Yang

et al. 2019

Cell Stress and Chaperones

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Stem cells from human exfoliated deciduous teeth (SHEDs) are a promising source for tissue engineering and stem cell transplantation. However, long-term in vitro culture and expansion lead to the loss of stemness of SHEDs, compromising their therapeutic benefits. Hypoxia plays an essential role in controlling the stem cell behavior of mesenchymal stem cells (MSCs). Thus, this study aimed to investigate the effects of cobalt chloride (CoCl 2), a hypoxia-mimetic agent, on the stem cell marker expression and osteogenic differentiation of SHEDs. SHEDs were cultured with or without 50 or 100 μM CoCl 2. Their proliferation, apoptosis, stem cell marker expression, migration ability, and osteogenic differentiation were examined. Culture with 50 and 100 μM CoCl 2 increased the hypoxiainducible factor-1 alpha (HIF-1α) protein levels in a dose-dependent manner in SHEDs without inducing significant cytotoxicity. This effect was accompanied by an increase in the proportion of STRO-1 + cells. CoCl 2 significantly increased the expression of stem cell markers (OCT4, NANOG, SOX2, and c-Myc) in a dose-dependent manner. The migration ability was also promoted by CoCl 2 treatment. Furthermore, SHEDs cultured in osteogenic medium with CoCl 2 showed a dose-dependent reduction in alkaline phosphatase (ALP) activity and calcium deposition. The expression of osteogenic-related genes was also suppressed by CoCl 2 , especially in the 100-μM CoCl 2 group. In conclusion, CoCl 2 increased the expression of stem cell markers and inhibited the osteogenic differentiation of SHEDs. These findings may provide evidence supporting the use of in vitro hypoxic environments mimicked by CoCl 2 in assisting the clinical application of SHEDs.

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Cobalt Chloride Enhances the Stemness of Human Dental Pulp Cells

Cited by 23 publications

References 35 publications

The Hypoxia-Mimetic Agent Cobalt Chloride Differently Affects Human Mesenchymal Stem Cells in Their Chondrogenic Potential

The Hypoxia-Mimetic Agent Cobalt Chloride Differently Affects Human Mesenchymal Stem Cells in Their Chondrogenic Potential

Succinate Supplement Elicited “Pseudohypoxia” Condition to Promote Proliferation, Migration, and Osteogenesis of Periodontal Ligament Cells

Effects of cobalt chloride on the stem cell marker expression and osteogenic differentiation of stem cells from human exfoliated deciduous teeth

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