Effect of Metformin on Proliferation of Skin Derived Stem Cells in the Case of Normoxia and Hypoxia

Abu-Zaiton, Ahmed

doi:10.3923/jbs.2014.149.153

Cited by 3 publications

(8 citation statements)

References 14 publications

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“…Besides, we have demonstrated that the longer treatment with metformin (72 hours) has not changed the effect of metformin on MSCs (Figure ). These findings are in agreement with Abu‐Zaiton and his colleagues reporting that metformin cell growth inhibition has not changed with time in fibroblast stem cells . As Benjamin has suggested, there is a delay between activation of AMPK and induction of cell death pathway by metformin, and apoptosis is remarkable after 24 hours in primary β cells; however, our results do not show cytotoxicity at 24 hours, and metformin shows growth inhibition after 48‐hour exposure.…”

Section: Discussionsupporting

confidence: 93%

“…These findings are in agreement with Abu-Zaiton and his colleagues reporting that metformin cell growth inhibition has not changed with time in fibroblast stem cells. 40 42 In this regards, celecoxib has shown antitumor activity in different cell lines by activation of caspase 3 and induction of apoptosis as well as cell cycle arrest. 43 The type 2 diabetes has been shown to be associated by inflammatory pathways including COX-2 activity.…”

Section: Celecoxib Induced Secretion Of Gdf-15 From Mscs In Each Glmentioning

confidence: 99%

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Effect of metformin and celecoxib on cytotoxicity and release of GDF‐15 from human mesenchymal stem cells in high glucose condition

Zafarvahedian

Roohi

Sepand

et al. 2017

Cell Biochemistry & Function

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Mesenchymal stem cells (MSCs) have therapeutic potential for treatment of diabetes. However, in vitro behavior of MSCs in high glucose condition as well as presence of glucose lowering agents is not fully understood. Because MSCs have an important role in tissue repair, we examined the effects of metformin and celecoxib on viability of MSCs in different glucose conditions. MSCs, from umbilical cord blood, were cultured in normoglycemic (glucose 5.5 mM), midglycemic (glucose 10 mM), and hyperglycemic (glucose 25 mM) conditions, and the cell viability was evaluated by MTT assay. The cytotoxicity and secretion of GDF-15 were further tested in MSCs treated with metformin and celecoxib in various glucose concentrations. Our results showed that high glucose condition lowered viability of MSCs. Metformin treatment also inhibited proliferation of MSCs, but its toxicity was not changed in high glucose condition. Celecoxib induced cytotoxicity in MSCs, and the toxicity was increased in high glucose condition. Metformin and celecoxib induced release from MSCs; however, high glucose inhibited the metformin-induced GDF-15 release. These findings suggested that metformin did not increase the cytotoxicity of high glucose condition in MSCs. Moreover, celecoxib treatment in diabetic condition can reduce the viability of MSCs to proliferate and regenerate perhaps via change in release of GDF-15.

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Section: Discussionsupporting

confidence: 93%

Section: Celecoxib Induced Secretion Of Gdf-15 From Mscs In Each Glmentioning

confidence: 99%

Effect of metformin and celecoxib on cytotoxicity and release of GDF‐15 from human mesenchymal stem cells in high glucose condition

Zafarvahedian

Roohi

Sepand

et al. 2017

Cell Biochemistry & Function

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“…The addition of 1 mM and 5 mM doses decreased proliferative activity of mouse BMSCs but only after 72 hours of propagation. Recently, Abu-Zaiton [ 40 ] showed that the proliferation of dermal fibroblasts is affected by metformin in a dose-dependent manner. Our results showed that metformin at a concentration of 1 mM and 5 mM exerted comparable effect on the proliferative activity of Balb/3T3 fibroblasts.…”

Section: Discussionmentioning

confidence: 99%

“…The influence of metformin on physiology of BMSCs and fibroblasts has been thus far predominantly studied in the context of their proliferation [ 38 , 40 ]. However, these studies used lower concentration of metformin and experiments were performed independently.…”

Section: Discussionmentioning

confidence: 99%

“…We argue that the analysis of cellular organization should be a key parameter when determining the effects of active agents, such as metformin, even though the evaluation of cell proliferation and gene expression becomes an important complement to such analysis. Detailed investigation of cell morphology is often neglected, due to the difficult and time-consuming techniques or is sometimes reduced to the analysis of cell shapes and growth patterns with an inverted light or fluorescence microscope, as in the papers discussed [ 38 , 40 ]. To the best of our knowledge, the present study is the first report showing morphological and ultrastructural changes of BMSCs and Balb/3T3 fibroblasts under the influence of metformin.…”

Section: Discussionmentioning

confidence: 99%

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Effect of Metformin on Viability, Morphology, and Ultrastructure of Mouse Bone Marrow-Derived Multipotent Mesenchymal Stromal Cells and Balb/3T3 Embryonic Fibroblast Cell Line

Śmieszek

Czyrek

Basinska

et al. 2015

BioMed Research International

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Metformin, a popular drug used to treat diabetes, has recently gained attention as a potentially useful therapeutic agent for treating cancer. In our research metformin was added to in vitro cultures of bone marrow-derived multipotent mesenchymal stromal cells (BMSCs) and Balb/3T3 fibroblast at concentration of 1 mM, 5 mM, and 10 mM. Obtained results indicated that metformin negatively affected proliferation activity of investigated cells. The drug triggered the formation of autophagosomes and apoptotic bodies in all tested cultures. Additionally, we focused on determination of expression of genes involved in insulin-like growth factor 2 (IGF2) signaling pathway. The most striking finding was that the mRNA level of IGF2 was constant in both BMSCs and Balb/3T3. Further, the analysis of IGF2 concentration in cell supernatants showed that it decreased in BMSC cultures after 5 and 10 mM metformin treatments. In case of Balb/3T3 the concentration of IGF2 in culture supernatants decreased after 1 and 5 mM and increased after 10 mM of metformin. Our results suggest that metformin influences the cytophysiology of somatic cells in a dose- and time-dependent manner causing inhibition of proliferation and abnormalities of their morphology and ultrastructure.

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In VitroandIn VivoEffects of Metformin on Osteopontin Expression in Mice Adipose-Derived Multipotent Stromal Cells and Adipose Tissue

Śmieszek

Basinska

Chrząstek

et al. 2015

Journal of Diabetes Research

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Metformin is applied not only as antidiabetic drug, but also in the treatment of obesity or as antiaging drug. The first part of the research discussed the effect of metformin at concentrations of 1 mM, 5 mM, and 10 mM on the morphology, ultrastructure, and proliferation potential of mice adipose-derived multipotent mesenchymal stromal cells (ASCs) in vitro. Additionally, we determined the influence of metformin on mice adipose tissue metabolism. This study has shown for the first time that metformin inhibits the proliferative potential of ASCs in vitro in a dose- and time-dependent manner. In addition, we have found a significant correlation between the activity of ASCs and osteopontin at the mRNA and protein level. Furthermore, we have demonstrated that 5 mM and 10 mM metformin have cytotoxic effect on ASCs, causing severe morphological, ultrastructural, and apoptotic changes. The reduced level of OPN in the adipose tissue of metformin-treated animals strongly correlated with the lower expression of Ki67 and CD105 and increased caspase-3. The metformin influenced also circulating levels of OPN, which is what was found with systemic and local action of metformin. The results are a valuable source of information regarding the in vitro effect of metformin on adipose-derived stem cells.

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Effect of Metformin on Proliferation of Skin Derived Stem Cells in the Case of Normoxia and Hypoxia

Cited by 3 publications

References 14 publications

Effect of metformin and celecoxib on cytotoxicity and release of GDF‐15 from human mesenchymal stem cells in high glucose condition

Effect of metformin and celecoxib on cytotoxicity and release of GDF‐15 from human mesenchymal stem cells in high glucose condition

Effect of Metformin on Viability, Morphology, and Ultrastructure of Mouse Bone Marrow-Derived Multipotent Mesenchymal Stromal Cells and Balb/3T3 Embryonic Fibroblast Cell Line

In VitroandIn VivoEffects of Metformin on Osteopontin Expression in Mice Adipose-Derived Multipotent Stromal Cells and Adipose Tissue

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