Effects of hypoxic culture conditions on umbilical cord-derived human mesenchymal stem cells

Abstract

Following cultivation of distinct mesenchymal stem cell (MSC) populations derived from human umbilical cord under hypoxic conditions (between 1.5% to 5% oxygen (O2)) revealed a 2- to 3-fold reduced oxygen consumption rate as compared to the same cultures at normoxic oxygen levels (21% O2). A simultaneous measurement of dissolved oxygen within the culture media from 4 different MSC donors ranged from 15 μmol/L at 1.5% O2 to 196 μmol/L at normoxic 21% O2. The proliferative capacity of the different hypoxic MSC populations was elevated as compared to the normoxic culture. This effect was paralleled by a significantly reduced cell damage or cell death under hypoxic conditions as evaluated by the cellular release of LDH whereby the measurement of caspase3/7 activity revealed little if any differences in apoptotic cell death between the various cultures. The MSC culture under hypoxic conditions was associated with the induction of hypoxia-inducing factor-alpha (HIF-1α) and an elevated expression of energy metabolism-associated genes including GLUT-1, LDH and PDK1. Concomitantly, a significantly enhanced glucose consumption and a corresponding lactate production could be observed in the hypoxic MSC cultures suggesting an altered metabolism of these human stem cells within the hypoxic environment.

Use of poly(DL-lactide-ε-caprolactone) membranes and mesenchymal stem cells from the Wharton's jelly of the umbilical cord for promoting nerve regeneration in axonotmesis: In vitro and in vivo analysis

“…Several factors, such as inhibition of oxidative phosphorylation due to defects in mitochondrial DNA, dysfunctional Krebs cycle, or inactivation of p53 have been suggested to contribute to the glycolytic switch occurr during cellular expansion and differen-tiation ( Funes et al, 2007). Recently, it has been shown that umbilical-cord derived mesenchymal stem cells adapt their oxygen consumption and energy metabolism to the available oxygen concentrations ( Lavrentieva et al, 2010). In our conditions, HMSCs consumed glucose at higher rates during the first 48 h of expansion.…”

Viability and neural differentiation of mesenchymal stem cells derived from the umbilical cord following perinatal asphyxia

“…A recent study reported a significantly reduced rate of proliferation in severely hypoxic medium with the accumulation of G1 phase cells, 28 which is similar to our findings. Others 20,21 have demonstrated that UCB-derived human MSCs can adapt to a physiologically hypoxic environment by altering their energy consumption and metabolism.…”

“…Previous work examined the ability of MSCs to proliferate and differentiate when exposed to in vitro hypoxic conditions. 20,21 Infusion of MSCs at 3 and 10 days post-hypoxic-ischemic injury was recently shown to enhance cell proliferation, survival and differentiation. 10 It was originally hypothesized that regeneration occurs directly by incorporation of MSC-derived neurons and oligodendrocytes to restore damage.…”

Hypoxic and ischemic effects on gene and protein expression levels of paracrine factors by human olfactory mucosa mesenchymal-like stem cells

“…12 Hypoxia 13 can affect the secretion of paracrine factors, 14 alter gene expression of MSCs 15,16 and enhance proliferation of MSCs. [17][18][19][20][21] The amount of serum present in the culture media also affects stem cell behavior. When MSCs are cultured in 10% serum, some factors may not be present.…”