TABLE 2.

Effect of copper increase on proliferation and differentiation in different cell types.

Cells	[Cu]	Features	Proliferation	Differentiation	References
Studies in primary cells
MSC (mesenchymal stem cells)	50 µM Cu-His	Present in the mesodermal germinal layer	↓	↑ into osteoblasts or adipocytes	Rodríguez et al. (2002)
MEFs (Mouse embryonic fibroblasts)	10 µM CuCl2	Synthesize fibers and maintain matrix	↑	−	Itoh et al. (2008)
HUVEC	500 µM CuSO4	Human umbilical vein endothelial cells	↑	−	Hu (1998)
HPC (CD34+)	10 µM CuCl2	Hematopoietic progenitor cells	↓	↑	Peled et al. (2002); Peled et al. (2005)
HSC	10 µM CuCl2	Hematopoietic stem cells	↓	↑	Huang et al. (2009)
RIP1–Tag2 mice	20 µM Cu via drinking water from 4 to 15 weeks of age	Tumorigenetic mouse model of pancreatic islet cell carcinoma	↑ promotes tumor growth	−	Ishida et al. (2013)
Astrocytes	30 μM CuCl2	Astroglia from rat cerebral cortex	↑	−	Hu et al. (2016)
BMECs	30–120 µM CuCl2	Brain microvascular endothelial cells from rat	↑	−	Wang et al. (2016)
Studies in cell lines from cancer
HepG2	64 µM CuSO4	Human liver hepatocellular cells	↓	−	Aston et al. (2000); Arnal et al. (2012)
K562	95 µM CuCl2	Human erythroleukemia cell line	↑	↓	Ruiz et al. (2016)
A-549	80 µM Cu	Adenocarcinomic human alveolar basal epithelial cells	↓	−	Arnal et al. (2012)
HL-60	12 μM Cu(NO3)2	Human promyelocytic leukemia cells	↓	↑	Bae and Percival (1993)
Huh-7 and OUMS29	300 µM CuSO4	Human hepatoma cell lines	↓	−	Oe et al. (2016)
A-549	5–15 µM CuCl2	Adenocarcinomic human alveolar basal epithelial cells	↑	−	Zhang et al. (2016)

↑: increase; ↓: decrease.