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Related Concept Videos

Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl hydroxylase and factor...
Mechanism of Angiogenesis01:10

Mechanism of Angiogenesis

Blood vessel formation starts early during embryonic development, around day 7. In the extraembryonic yolk sac, mesodermal precursor cells called hemangioblast proliferate and differentiate into angioblast. Angioblasts express vascular endothelial growth factor receptor 2 or VEGFR2, which binds VEGF-A, a proangiogenic factor, guiding blood vessel formation. VEGF signaling promotes angioblasts to form a blood island in the developing embryo. Angioblasts further differentiate, giving rise to...

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Aging-related decrease of human ASC angiogenic potential is reversed by hypoxia preconditioning through ROS

Sandra De Barros1, Stéphanie Dehez, Emmanuelle Arnaud

  • 1STROMAlab, UMR Université Paul Sabatier/CNRS 5273, BP 84 225 - F-31 432, Toulouse, France.

Molecular Therapy : the Journal of the American Society of Gene Therapy
|October 17, 2012
PubMed
Summary
This summary is machine-generated.

Aging impairs the blood vessel-forming ability of adipose stem cells (ASCs). Hypoxic preconditioning can reverse this age-related decline in ASCs, offering potential for regenerative therapies.

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Area of Science:

  • Regenerative Medicine
  • Cell Biology
  • Vascular Biology

Background:

  • Adipose-derived stem cells (ASCs) are promising for cell-based therapies due to their autologous nature and ability to promote neovascularization.
  • Aging diminishes the regenerative capacity of mesenchymal stem cells (MSCs), raising concerns about age-related effects on ASC function.

Purpose of the Study:

  • To investigate the impact of donor age on the angiogenic potential of human ASCs (hASCs).
  • To elucidate the underlying mechanisms responsible for age-related decline in hASC angiogenic function.
  • To evaluate the efficacy of hypoxic preconditioning in restoring the angiogenic capacity of aged hASCs.

Main Methods:

  • Transplantation of hASCs into a mouse ischemic hindlimb model to assess in vivo neovascularization.
  • In vitro analysis of hASC differentiation, proliferation, factor secretion, and oxidative stress.
  • Evaluation of hypoxic preconditioning effects on hASC angiogenic potential and reactive oxygen species (ROS) generation.

Main Results:

  • Aging significantly impaired the in vivo angiogenic capacity of hASCs in a mouse model of ischemic injury.
  • In vitro, aging reduced hASC differentiation into endothelial cells, decreased secretion of proangiogenic factors, and increased oxidative stress.
  • Hypoxic preconditioning successfully restored the in vivo angiogenic function of aged hASCs, an effect linked to modulation of ROS generation.

Conclusions:

  • Donor age negatively impacts the angiogenic potential of human ASCs, compromising their therapeutic efficacy in ischemic conditions.
  • Reduced differentiation, altered factor secretion, and increased oxidative stress are key mechanisms underlying age-related functional decline in hASCs.
  • Hypoxic preconditioning represents a viable strategy to counteract age-associated deficits in hASC angiogenic capacity by modulating ROS signaling.