Modulation of the proliferation and differentiation of human mesenchymal stem cells by copper

Abstract

Copper plays important functional roles in bone metabolism and turnover. It is known that it is essential for normal growth and development of the skeleton in humans and in animals. Although at present the exact role that copper plays in bone metabolism is unknown, bone abnormalities are a feature of severe copper deficiency. Osteoblasts are derived from mesenchymal stem cells (MSCs) present in bone marrow stroma, which are able to differentiate into bone, adipocytes, and other cell phenotypes. Excess adipogenesis in postmenopausal women may occur at the expense of osteogenesis and, therefore, may be an important factor in the fragility of postmenopausal bone. The purpose of this study was to evaluate whether an increase of the extracellular concentration of copper affects the ability of MSCs to differentiate into osteoblasts or adipocytes. The results showed that copper modified both the differentiation and the proliferative activity of MSCs obtained from postmenopausal women. Copper (50 microM) diminished the proliferation rate of MSCs, increasing their ability to differentiate into the osteogenic and the adipogenic lineages. Copper induced a 2-fold increase in osteogenic differentiation of MSCs, measured as a increase in calcium deposition. Copper (5 and 50 microM) diminished the expression of alkaline phosphatase (50 and 80%, respectively), but induced a shift in the expression of this enzyme to earlier times during culture. Copper also induced a 1.3-fold increase in the adipogenic differentiation of MSCs. It is concluded that copper stimulates MSC differentiation, and that this is preferentially towards the osteogenic lineage.

Aromatase activity of human mesenchymal stem cells is stimulated by early differentiation, vitamin D and leptin

“…The ability of hMSCs to differentiate into the osteoblastic lineage in vitro was evaluated by measuring alkaline phosphatase activity, as an early osteogenic differentiation marker (Hu et al 2003). At the indicated time (7 days of culture), the culture medium was removed and alkaline phosphatase activity was measured as previously described (Rodríguez et al 2002).…”

The Combination of Electric Current and Copper Promotes Neuronal Differentiation of Adipose-Derived Stem Cells

“…Adipose tissue is one of the most accessible sources for stem cells with high proliferative capacity and multilineage potential 8,32 . Pluripotent ADSCs are currently investigated as a promising cell source for clinical application, and they have the capability of neuronal differentiation 3,20,34 .…”

“…It has been shown that copper is needed for the neurite outgrowth mediated by nerve growth factor signal transduction 5 . Copper is also found to modulate the osteogenic and adipogenic differentiation of mesenchymal stem cells 32 . Presence of copper may be important already at the early stages of stem cell differentiation as it may take part in both the commitment and maturation steps of the differentiation process.…”

“…Presence of copper may be important already at the early stages of stem cell differentiation as it may take part in both the commitment and maturation steps of the differentiation process. 32 Copper, that binds with high affinity to phosphatidylserine (PS), phospholipid enriched especially in neuronal membranes 27 , may be needed to initiate the ADSC differentiation towards neuronal lineage. In addition, mammalian copper transporter Ctr1 that has been found at plasma membranes and that is responsible of copper transport into the cell, has been suggested to be important in signal transduction mechanism involved in stem cell differentiation 11 In this study, we investigated the possibilities of using the combination of electric fields and copper to promote the neuronal differentiation of adult stem cells.…”

A novel nano-copper-bearing stainless steel with reduced Cu2+ release only inducing transient foreign body reaction via affecting the activity of NF-κB and Caspase 3

“…13,14 Nevertheless, Cu has been widely used in female intrauterine devices as an implant material 15 which can effectively disturb the fertilization process or zygote cots through the sperm cytotoxicity of Cu ions or worsening of the endometrial inflammatory response. Cu was determined to provide good antibacterial properties 16,17 and osteogenic properties 18,19 which has prompted many researchers to make an effort to add Cu into the orthopedic implant materials in anticipation of achieving some improved biological activities. Some scholars attempted to add a Cu coating onto the surface of orthopedic implants through different processing techniques.…”