Hypoxia-mimetic agents inhibit proliferation and alter the morphology of human umbilical cord-derived mesenchymal stem cells

Abstract

BackgroundThe therapeutic efficacy of human mesenchymal stem cells (hMSCs) for the treatment of hypoxic-ischemic diseases is closely related to level of hypoxia in the damaged tissues. To elucidate the potential therapeutic applications and limitations of hMSCs derived from human umbilical cords, the effects of hypoxia on the morphology and proliferation of hMSCs were analyzed.ResultsAfter treatment with DFO and CoCl2, hMSCs were elongated, and adjacent cells were no longer in close contact. In addition, vacuole-like structures were observed within the cytoplasm; the rough endoplasmic reticulum expanded, and expanded ridges were observed in mitochondria. In addition, DFO and CoCl2 treatments for 48 h significantly inhibited hMSCs proliferation in a concentration-dependent manner (P < 0.05). This treatment also increased the number of cells in G0/G1 phase and decreased those in G2/S/M phase.ConclusionsThe hypoxia-mimetic agents, DFO and CoCl2, alter umbilical cord-derived hMSCs morphology and inhibit their proliferation through influencing the cell cycle.

Novel therapeutic core–shell hydrogel scaffolds with sequential delivery of cobalt and bone morphogenetic protein-2 for synergistic bone regeneration

“…3). Several studies have also reported the Co ion-induced suppression of cellular growth and the significant dose-dependent toxicity behaviors (1 to 100 µM Co ions) [16,29]. While suppressing a certain level of cellular viability, the Co has also been shown to significantly improve the angiogenesis, including VEGF production through the hypoxicinduced HIF-1α pathway [29].…”

“…In fact, studies have used Co ions (CoCl 2 ) to simulate hypoxic cell culture conditions, where the common concentration used was 100 µM [15,16,28]. Taking the release amount of Co ions into consideration from our results (Fig.…”

“…While excessive uses of Co may induce cell death, small concentrations used in the therapeutic window (reported to be less than 100 µM) are expected to have profound positive effects [15,16]. We report this novel design of Co/BMP2 sequential delivering scaffold, in terms of the process tools, effects on cellular angiogenesis and osteogenesis, and in vivo efficacy in bone regeneration.…”

The effect of hypoxia preconditioning on the neural and stemness genes expression profiling in human umbilical cord blood mesenchymal stem cells

“…MSCs exposed to hypoxic conditions exhibit greater colony-forming potential and proliferate faster and longer. Exposure of MSCs to hypoxia also prolonged their differentiation [10]. The mechanism of the therapeutic benefits of HPC must be multifaceted, at least enhanced expression and release of trophic and growth factors that provide autocrine and paracrine effects of protection and motivation of regenerative responses [11].…”

c-kit positive cardiac stem cells as a potential candidate for heart repair, developments, challenges and future implications

“…In view of the fact that DFO belongs to a class of hypoxia mimetic agents which also inhibit cell proliferation 21 , Song et al 6 chose another iron chelator mimosine (MIM) structurally different from DFO.…”