The angiogenic properties of mesenchymal stem/stromal cells and their therapeutic potential

Abstract

Characterization of MSCs' in vivo origins and biological properties in relation to their localization within tissue niches, reprogramming strategies and newer imaging/bioengineering approaches.

The Hematopoietic Chemokine CXCL12 Promotes Integration of Human Endothelial Colony Forming Cell–Derived Cells into Immature Vessel Networks

“…Our approach to examining the effects of AMD3100 in a complex in vitro microenvironmental model of neovascularization may prove significant for understanding the mechanisms of action of this and other drugs and associated molecules in promoting or inhibiting revascularization and for more clearly defining the experimental approach to testing or assessing the effects of such drugs in vitro and subsequently in vivo. Understanding such mechanisms as those exemplified here with CXCL12 in new blood vessel formation has translational implications that include inhibition of tumor progression and promotion of tissue repair and regeneration as diverse as peripheral arterial disease and ischemic injury, burn injury, neurodegenerative disease, and hematological regeneration [5][6][7]11,18,22,[56][57][58][59][60].…”

“…Blood vessel growth takes place by different mechanisms, which include vasculogenesis or de novo blood vessel formation from endothelial progenitor cells, angiogenesis (intussusceptive angiogenesis or sprouting of existing vessels), and arteriogenesis (the growth of collateral vessels in response to occlusion of major arteries and associated with endothelial and smooth muscle cell proliferation), and, during tumor growth, by vascular mimicry or blood vessel cooption [19][20][21][22]. For sprouting angiogenesis, the extracellular matrix surrounding the vasculature is degraded and mural cells detach from capillaries and microvessels (<100 mm in diameter) allowing the endothelial tip cells to become invasive and to form filopodia and lamellipodia in response to guidance cues, while stalk cells that lie behind the tip cells increase in number, extend the vessels, and form extracellular matrix, junctions, and lumens [19][20][21][22].…”

“…For sprouting angiogenesis, the extracellular matrix surrounding the vasculature is degraded and mural cells detach from capillaries and microvessels (<100 mm in diameter) allowing the endothelial tip cells to become invasive and to form filopodia and lamellipodia in response to guidance cues, while stalk cells that lie behind the tip cells increase in number, extend the vessels, and form extracellular matrix, junctions, and lumens [19][20][21][22]. Once the tip cells anastomose or inosculate with other tip cells [23], vessel maturation takes place and this involves mural cell recruitment, extracellular matrix deposition, and the commencement of blood flow.…”

Exosomes secreted by mesenchymal stem cells promote endothelial cell angiogenesis by transferring miR-125a

“…Each of the steps involves a complex interaction between endothelial cells and their corresponding extracellular environment (Patel-Hett and D'Amore, 2011). Several types of cells, such as mesenchymal stem cells (MSCs), have been identified as creating specific microenvironments to control blood vessel density and function (Bronckaers et al, 2014;Watt et al, 2013). Understanding how blood vessels communicate with MSCs in their surrounding microenvironment is a major challenge for diseases involving angiogenesis.…”

Therapeutically targeting SELF‐reinforcing leukemic niches in acute myeloid leukemia: A worthy endeavor?

“…Intriguingly, this MSC loss detected at clinical diagnosis is heterogeneous and prognostically significant: a low MSC number after initial treatment predicts a long complete remission, whereas a high MSC number predicts a high relapse probability. Thus, it can be argued that MSCs might significantly affect MRD persistence either through their angiogenic or immunosuppressive/anti-inflammatory properties [60,61]. It is well-known that MSCs actively participate in the "angiogenic switch" not only by releasing various angiogenic factors [62], but also by recruiting circulating vascular progenitor cells [63].…”