Editors' ChoiceTissue Engineering

A twist of fat(e): Liposuction to treat vascular disease

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Science Translational Medicine  26 Oct 2016:
Vol. 8, Issue 362, pp. 362ec170
DOI: 10.1126/scitranslmed.aai9167

Clogged arteries limit blood flow, starving tissues of oxygen and leading to heart attacks, strokes, and other vascular complications. Treatments to bypass obstructed arteries use autologous vessels harvested from other body sites or synthetic grafts in the absence of adequate donor vessels. When small vessels are required, the use of synthetic grafts may present complications due to insufficient graft strength or a tendency to clot if lacking an endothelial cell lining. To create more suitable small diameter grafts from autologous cells, Zhou et al. engineered vessels from human fat.

The team used established techniques to isolate human adipose–derived stem cells (hASC) from lipoaspirated fat tissue. They coaxed hASCs to differentiate into smooth muscle cells (SMC) and endothelial cells (EC) using a combination of growth factors; a low oxygen culture environment produced normal EC functions, such as nitric oxide production. To form an engineered vessel, Zhou and colleagues used pulsatile flow conditions to culture a biodegradable mesh seeded with SMCs around a silicone tube for 6 to 8 weeks. After the silicone tube was removed and the mesh degraded, a hollow cylinder of SMCs held together by SMC-derived extracellular matrix remained. In a key step, ECs were then injected into the lumen of the SMC cylinder and the assembly was cultured for an additional 1 to 2 weeks.

The resulting vessel had an inner EC layer and an outer SMC layer containing collagen, with both layers expressing appropriate cell type–specific markers. Compared with static conditions, culturing the mesh-embedded SMC construct under pulsatile flow led to greater collagen, prostaglandin I2, and nitric oxide content. The engineered vessels had greater mean elastic modulus, suture retention strength, and resistance to bursting than vessels cultured under static conditions, and these properties were attributed to the rich extracellular matrix produced under pulsatile conditions.

Fat is an attractive cell source for blood vessel engineering because it is found abundantly within the body and removal via lipoaspiration can be an elective procedure that does not pose significant risk to patient health. The ability to use an autologous tissue source and the absence of synthetic materials in the resulting engineered vessels suggest the adipose-derived vessels will be well tolerated by the body; however, long-term implantation studies are required to establish safety and durability. For patients with blocked arteries, shortening the 10-week fabrication time will be critical.

R. Zhou et al., Small diameter blood vessels bioengineered from human adipose-derived stem cells. Sci. Rep. 10.1038/srep35422 (2016). [Full Text]

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