Metformin enhances the osteogenesis and angiogenesis of human umbilical cord mesenchymal stem cells for tissue regeneration engineering

Tong, Lei; Deng, Shiwen; Chen, Peng; Xiao, Zhuangzhuang; Cai, Shanglin; Hang, Zhongci; Yang, Yanjie; Zhang, Xiaoshuang; Li, Quanhai; Du, Hongwu

doi:10.1016/j.biocel.2021.106086

Cited by 19 publications

(10 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Additionally, metformin promoted angiogenesis and improved the survival of random pattern skin flaps by activating the AMPK–mammalian target of rapamycin–transcription factor EB signaling pathway ( 20 ). Moreover, low-dose metformin significantly enhanced the angiogenic differentiation of mesenchymal stem cells in vivo and in vitro and boosted mesenchymal stem cell-mediated promotion of HUVEC migration and tube formation by upregulating the expression of stem cell factor and vascular endothelial growth factor receptor 2 ( 21 ).…”

Section: Discussionmentioning

confidence: 99%

Metformin Promotes Mechanical Stretch-Induced Skin Regeneration by Improving the Proliferative Activity of Skin-Derived Stem Cells

et al. 2022

View full text Add to dashboard Cite

BackgroundSkin expansion by mechanical stretch is an essential and widely used treatment for tissue defects in plastic and reconstructive surgery; however, the regenerative capacity of mechanically stretched skin limits clinical treatment results. Here, we propose a strategy to enhance the regenerative ability of mechanically stretched skin by topical application of metformin.MethodsWe established a mechanically stretched scalp model in male rats (n = 20), followed by their random division into two groups: metformin-treated (n = 10) and control (n = 10) groups. We measured skin thickness, collagen volume fraction, cell proliferation, and angiogenesis to analyze the effects of topical metformin on mechanically stretched skin, and immunofluorescence staining was performed to determine the contents of epidermal stem cells and hair follicle bulge stem cells in mechanically stretched skin. Western blot was performed to detect the protein expression of skin-derived stem cell markers.ResultsCompared with the control group, metformin treatment was beneficial to mechanical stretch-induced skin regeneration by increasing the thicknesses of epidermis (57.27 ± 10.24 vs. 31.07 ± 9.06 μm, p < 0.01) and dermis (620.2 ± 86.17 vs. 402.1 ± 22.46 μm, p < 0.01), number of blood vessels (38.30 ± 6.90 vs. 17.00 ± 3.10, p < 0.01), dermal collagen volume fraction (60.48 ± 4.47% vs. 41.28 ± 4.14%, p < 0.01), and number of PCNA+, Aurora B+, and pH3+ cells. Additionally, we observed significant elevations in the number of proliferating hair follicle bulge stem cells [cytokeratin (CK)15+/proliferating cell nuclear antigen (PCNA)+] (193.40 ± 35.31 vs. 98.25 ± 23.47, p < 0.01) and epidermal stem cells (CK14+/PCNA+) (83.00 ± 2.38 vs. 36.38 ± 8.96, p < 0.01) in the metformin-treated group, and western blot results confirmed significant increases in CK14 and CK15 expression following metformin treatment.ConclusionTopical application of metformin enhanced the regenerative capacity of mechanically stretched skin, with the underlying mechanism possibly attributed to improvements in the proliferative activity of skin-derived stem cells.

show abstract

Section: Discussionmentioning

confidence: 99%

Metformin Promotes Mechanical Stretch-Induced Skin Regeneration by Improving the Proliferative Activity of Skin-Derived Stem Cells

et al. 2022

View full text Add to dashboard Cite

show abstract

“…The GFP–GMSCs cells used in the experiment were constructed from our laboratory, and the GFP protein was inserted into the GMSCs coding sequence through a lentiviral vector, and the GFP protein was stably expressed. In the drug induction experiment, the optimal concentration of metformin is 100 mM [ 42 ], and the concentration of growth factor is 10 ng/mL according to previous studies [ 43 ].…”

Section: Methodsmentioning

confidence: 99%

Chitosan Hydrogel Supplemented with Metformin Promotes Neuron–like Cell Differentiation of Gingival Mesenchymal Stem Cells

Cai

Tong

et al. 2022

IJMS

Self Cite

View full text Add to dashboard Cite

Human gingival mesenchymal stem cells (GMSCs) are derived from migratory neural crest stem cells and have the potential to differentiate into neurons. Metformin can inhibit stem–cell aging and promotes the regeneration and development of neurons. In this study, we investigated the potential of metformin as an enhancer on neuronal differentiation of GMSCs in the growth environment of chitosan hydrogel. The crosslinked chitosan/β–glycerophosphate hydrogel can form a perforated microporous structure that is suitable for cell growth and channels to transport water and macromolecules. GMSCs have powerful osteogenic, adipogenic and chondrogenic abilities in the induction medium supplemented with metformin. After induction in an induction medium supplemented with metformin, Western blot and immunofluorescence results showed that GMSCs differentiated into neuron–like cells with a significantly enhanced expression of neuro–related markers, including Nestin (NES) and β–Tubulin (TUJ1). Proteomics was used to construct protein profiles in neural differentiation, and the results showed that chitosan hydrogels containing metformin promoted the upregulation of neural regeneration–related proteins, including ATP5F1, ATP5J, NADH dehydrogenase (ubiquinone) Fe–S protein 3 (NDUFS3), and Glutamate Dehydrogenase 1 (GLUD1). Our results help to promote the clinical application of stem–cell neural regeneration.

show abstract

“…Genes such as Runx2, alkaline phosphatase (ALP), and osteopontin (OPN) are usually regarded as osteogenic markers, and they play a critical position in the osteogenic differentiation of MSCs ( Vimalraj et al, 2015 ). Several studies have revealed that metformin has a role in promoting osteoblastogenesis in MSCs differentiation ( Cortizo et al, 2006 ; Gao et al, 2008 ; Gu et al, 2017 ; Lei et al, 2021 ). Metformin regulates the differentiation of MSCs to osteoblasts probably mediated by AMPK, bone morphogenetic proteins (BMPs), glycogen synthase kinase-3β(GSK3β), AKT, and ERK (As shown in Figure 1 ).…”

Section: Mechanisms Of Metformin Regulation Of the Musculoskeletal Sy...mentioning

confidence: 99%

The Function of Metformin in Aging-Related Musculoskeletal Disorders

Song

Zhao

2022

Front. Pharmacol.

View full text Add to dashboard Cite

Metformin is a widely accepted first-line hypoglycemic agent in current clinical practice, and it has been applied to the clinic for more than 60 years. Recently, researchers have identified that metformin not only has an efficient capacity to lower glucose but also exerts anti-aging effects by regulating intracellular signaling molecules. With the accelerating aging process and mankind’s desire for a long and healthy life, studies on aging have witnessed an unprecedented boom. Osteoporosis, sarcopenia, degenerative osteoarthropathy, and frailty are age-related diseases of the musculoskeletal system. The decline in motor function is a problem that many elderly people have to face, and in serious cases, they may even fail to self-care, and their quality of life will be seriously reduced. Therefore, exploring potential treatments to effectively prevent or delay the progression of aging-related diseases is essential to promote healthy aging. In this review, we first briefly describe the origin of metformin and the aging of the movement system, and next review the evidence associated with its ability to extend lifespan. Furthermore, we discuss the mechanisms related to the modulation of aging in the musculoskeletal system by metformin, mainly its contribution to bone homeostasis, muscle aging, and joint degeneration. Finally, we analyze the protective benefits of metformin in aging-related diseases of the musculoskeletal system.

show abstract

Metformin enhances the osteogenesis and angiogenesis of human umbilical cord mesenchymal stem cells for tissue regeneration engineering

Cited by 19 publications

References 53 publications

Metformin Promotes Mechanical Stretch-Induced Skin Regeneration by Improving the Proliferative Activity of Skin-Derived Stem Cells

Metformin Promotes Mechanical Stretch-Induced Skin Regeneration by Improving the Proliferative Activity of Skin-Derived Stem Cells

Chitosan Hydrogel Supplemented with Metformin Promotes Neuron–like Cell Differentiation of Gingival Mesenchymal Stem Cells

The Function of Metformin in Aging-Related Musculoskeletal Disorders

Contact Info

Product

Resources

About