| 19023021 |
Milovanova TN, Bhopale VM, Sorokina EM, Moore JS, Hunt TK, Hauer-Jensen M, Velazquez OC, Thom SR: Hyperbaric oxygen stimulates vasculogenic stem cell growth and differentiation in vivo. J Appl Physiol. 2009 Feb;106(2):711-28. Epub 2008 Nov 20.
We hypothesized that oxidative stress from hyperbaric oxygen (HBO (2), 2.8 ATA for 90 min daily) exerts a trophic effect on vasculogenic stem cells. In a mouse model, circulating stem/progenitor cell (SPC) recruitment and differentiation in subcutaneous Matrigel were stimulated by HBO (2) and by a physiological oxidative stressor, lactate. In combination, HBO (2) and lactate had additive effects. Vascular channels lined by CD34 (+) SPCs were identified. HBO (2) and lactate accelerated channel development, cell differentiation based on surface marker expression, and cell cycle entry. CD34 (+) SPCs exhibited increases in thioredoxin-1 (Trx1), Trx reductase, hypoxia-inducible factors (HIF)-1, -2, and -3, phosphorylated mitogen-activated protein kinases, vascular endothelial growth factor, and stromal cell-derived factor-1. Cell recruitment to Matrigel and protein synthesis responses were abrogated by N-acetyl cysteine, dithioerythritol, oxamate, apocynin, U-0126, neutralizing anti-vascular endothelial growth factor, or anti-stromal cell-derived factor-1 antibodies, and small inhibitory RNA to Trx reductase, lactate dehydrogenase, gp91 (phox), HIF-1 or -2, and in mice conditionally null for HIF-1 in myeloid cells. By causing an oxidative stress, HBO (2) activates a physiological redox-active autocrine loop in SPCs that stimulates vasculogenesis. Thioredoxin system activation leads to elevations in HIF-1 and -2, followed by synthesis of HIF-dependent growth factors. HIF-3 has a negative impact on SPCs. |
32(0,1,1,2) |