Defining the potential for cell therapy for vascular disease using animal models

Abstract

132Vascular cell delivery PERSPECTIVE sources would provide. Two major issues must be considered with regard to mature endothelial cells. First, will they have the plasticity to affect a therapeutic endpoint, and second have they been altered as a result of the underlying disease process. Nonetheless, multiple sources of mature endothelial cells exist. Venous endothelium has been harvested and used to populate biomaterial or synthetic vascular grafts (Herring et al., 1978;Graham et al., 1979;Belden et al., 1982;Noishiki et al., 1990a;Noishiki et al., 1990b;Noishiki et al., 1992), although endothelial cells may be quite limited in these settings (Zilla et al., 1987).Adipose tissue contains two potent sources of endothelial cells, namely resident microvascular endothelial cells and adipose-derived stromal cells (Miranville et al., 2004;Planat-Benard et al., 2004;Fraser et al., 2006;Wosnitza et al., 2007;Traktuev et al., 2008). In humans, the former may be defined as CD34+/CD45-cells that express CD31 and CD144. The adipose-derived stem cells (CD34+/CD45-/CD31-) share many properties with marrow stromal cells, are capable of endothelial differentiation, and are found in close proximity to endothelial cells (ECs) within adipose tissue.Given differences in endothelial cell phenotype and function according to tissue, matching the cell source to the intended cell phenotype may be important. For example, microvascular endothelial cells derived from tissues such as adipose may be relevant for therapeutic angiogenesis, given their highly proliferative nature and higher tube-forming capacity compared with large artery endothelial cells. By contrast, using arteryderived endothelial cells for relocation to another arterial system might be advantageous given the relatively poor ability to form new capillaries. Highly angiogenic cells might in theory promote adventitial and neointimal proliferation, promoting plaque expansion. In addition, large arterial endothelial cells express much higher amounts of the anti-atherosclerotic protein endothelialspecific nitric oxide synthase (eNOS) compared with microvascular endothelium (Gulati et al., 2003a). However, clinical applications of this approach may be limited by access to large arterial tissue.The ability to generate cells with an endothelial phenotype from peripheral blood would greatly simplify the harvesting process. In 1963 Stump and colleagues (Stump et al., 1963) demonstrated that endothelial colonies could be generated on small patches of Dacron within the lumen of an aortic interposition graft, which led the authors to postulate circulating blood as the endothelial source. Modern studies of animal and human chimeras using genetic markers and tagging have revealed that bone marrow-derived circulating progenitors may contribute to both endothelial and intimal smooth muscle cell formation in multiple models of vascular injury (Shi et al., 1998;Sata and Walsh, 2003).Asahara's landmark paper suggested that a CD34+ circulating cell subset contained endothelial precursor cells ...

Sox17 drives functional engraftment of endothelium converted from non-vascular cells

“…Engineered ECs that can be expanded, transplanted and engraft into compromised blood vessels to restore their perfusion and instructive functions could significantly alter how vascular diseases are studied, treated and cured12. As ECs play essential roles in organ development and regeneration, engineered engraftable ECs could help repair or replace injured tissue3456 or even reverse disease313233.…”

“…For many traumatic and ischemic vascular diseases, transplanting non-lymphatic blood vessel endothelial cells (ECs) is an attractive regenerative therapy, because vascularized and functional ECs support the metabolic needs of damaged tissues12 and choreograph tissue regrowth via perfusion-independent angiocrine functions34567. However, assessing EC transplantation therapies is made impractical by the difficulty of purifying and expanding primary ECs that sustain their vascular fate during in vitro cultivation.…”

The efficacy of extraembryonic stem cells in improving blood flow within animal models of lower limb ischaemia

“…ETSCs remain an abundant and valuable tool for regenerative therapy 30. In this study, we sought to assess the efficacy of ETSCs to treat PAD in animal models.…”

Magnetic nanoparticles for targeted vascular delivery

“…Rapid restoration of a continuous and functional endothelial layer can, thus, be essential for preventing thrombosis and inhibiting the progression of vessel renarrowing, which makes approaches aimed at facilitating the endothelium regeneration a potentially important therapeutic component of the obstructive vascular disease treatment (59,60).…”