Research ArticleTissue Engineering

Bioengineered human acellular vessels recellularize and evolve into living blood vessels after human implantation

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Science Translational Medicine  27 Mar 2019:
Vol. 11, Issue 485, eaau6934
DOI: 10.1126/scitranslmed.aau6934

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Vital vessels

Vascular access is critically important for hemodialysis. An arteriovenous fistula generated from native blood vessels has long been thought to be optimal for long-term access; however, some people with kidney disease require vascular grafts. Kirkton et al. studied bioengineered human acellular vessels (HAVs) implanted as hemodialysis access vessels in subjects with end-stage renal disease. Sixteen tissue samples from HAVs were explanted from subjects participating in phase 2 clinical studies over the course of nearly 4 years. The authors characterized cellular repopulation of the implanted vessels over time, noting increases in CD90+ cells, lumen-lining CD31+ endothelium, and the presence of aligned alpha smooth muscle actin–expressing cells. This study provides valuable insight into human vascular remodeling.

Abstract

Traditional vascular grafts constructed from synthetic polymers or cadaveric human or animal tissues support the clinical need for readily available blood vessels, but often come with associated risks. Histopathological evaluation of these materials has shown adverse host cellular reactions and/or mechanical degradation due to insufficient or inappropriate matrix remodeling. We developed an investigational bioengineered human acellular vessel (HAV), which is currently being studied as a hemodialysis conduit in patients with end-stage renal disease. In rare cases, small samples of HAV were recovered during routine surgical interventions and used to examine the temporal and spatial pattern of the host cell response to the HAV after implantation, from 16 to 200 weeks. We observed a substantial influx of alpha smooth muscle actin (αSMA)–expressing cells into the HAV that progressively matured and circumferentially aligned in the HAV wall. These cells were supported by microvasculature initially formed by CD34+/CD31+ cells in the neoadventitia and later maintained by CD34/CD31+ endothelial cells in the media and lumen of the HAV. Nestin+ progenitor cells differentiated into either αSMA+ or CD31+ cells and may contribute to early recellularization and self-repair of the HAV. A mesenchymal stem cell–like CD90+ progenitor cell population increased in number with duration of implantation. Our results suggest that host myogenic, endothelial, and progenitor cell repopulation of HAVs transforms these previously acellular vessels into functional multilayered living tissues that maintain blood transport and exhibit self-healing after cannulation injury, effectively rendering these vessels like the patient’s own blood vessel.

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