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Wang and colleagues demonstrated that hypoxic conditions (3% O 2 ) in rat MSC cultures increased proliferation by upregulating the mitogen-activated protein kinase (p38 MAPK) signaling pathway and inducing the nuclear translocation of hypoxia-inducible factor (HIF)-1a, key factors for cell proliferation, and the promotion ofdopaminergic neuronal differentiation

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These results are similar to prior studies utilizing WR-1065 in vitro and in vivo via retrograde ductal injection 19,51

On the contrary, proteins in the extracellular environment occur in the form of disulfide bridges