Program

SY8-2

Endothelial progenitor cells secretome as mediator of oligovascular remodeling

[Speaker] Anna Rosell:1
[Co-author] Takakuni Maki:2, Anna Morancho:1, Kazuhide Hayakawa:2, Alba Grayston:1, Joan Montaner:1, Eng H Lo:2, Ken Arai:2
1:Vall d'Hebron Research Institute, Spain, 2:Massachusetts General Hospital and Harvard Medical School, USA

EPCs are bone-marrow derived cells capable of differentiating ex vivo into endothelial-like cells becoming a model for endothelial generation and vascular repair. It is also accepted that EPCs can be incorporated into neovessels and their restorative actions on vascular remodeling have been widely reported in vivo in stroke models or traumatic brain injury.
At the same time, several nourishing factors have been reported to modulate EPCs function (such as VEGF or HMGB1), whereas other studies have demonstrated the benefit of factors secreted by EPCs (such as VEGF or HGF). In this regard, EPCs secretome mediates multiple cell-cell interactions playing a pivotal role to achieve brain remodeling including angiogenesis, neurogenesis or oligodendrogenesis in a whole neurorepair niche, in which other types of cells such as neurons, astrocytes, endothelial cells, pericytes and neural progenitor cells are comprised. More specifically the secretome of EPCs is known to stimulate endothelial cell migration, growth and function, to protect from axonal degeneration in cultured cortical neurons exposed to oxygen-glucose deprivation or promote tissue revascularization and recovery in ischemic tissues.
In the context of white matter remodeling, an endogenous pool of oligodendrocyte precursor cells (OPCs) is widely distributed in the adult brain for physiological myelin renewal and for repair under pathological conditions. In demyelinating disorders, residual OPCs tend to proliferate and differentiate into oligodendrocytes to alleviate white matter damage, however, the regeneration of oligodendrocytes and myelin sheaths might fail. One therapeutic strategy to boost this oligovascular remodeling are cell-based therapies, including EPCs secretome. In this regard we have identified the presence of several trophic, proteolytic and signaling factors in the EPC-CM that support the therapeutic effects on white matter remodeling. By using a combination of in vitro culture systems and an in vivo mouse model of chronic cerebral hypoperfusion targeting white matter degeneration we asked whether EPC secretome could enhance oligovascular proliferation, maturation and repair in damaged white matter. Our results demonstrate that the treatment with the EPC secretome preserves cognitive function and enhances oligo-angiogenesis in the injured white matter.

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