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

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.

Progressive Reinvention or Destination Lost? Half a Century of Cardiovascular Tissue Engineering

“…"Lifeline" grafts were disappointing though they were few. "Humacyte, " in contrast, had 60 access grafts implanted at 6 centers (325,326) and 20 femoro-popliteal grafts at 3 centers (327). Primary patencies were low both in the access grafts and in the femoro-popliteal grafts.…”

Geometry influences inflammatory host cell response and remodeling in tissue-engineered heart valves in-vivo

“…Macrophages play a pivotal role in the initiation and perpetuation of inflammation and remodeling processes, thereby determining either the chronicity or the resolution of the inflammatory process-and this has been demonstrated also for tissue-engineered implants such as vascular grafts [12][13][14][15][16][17][18] . In these studies, M2 macrophages were shown to help the recruitment of tissue remodeling cells (e.g.…”

Bioinspired Vascular Grafts

“…Notwithstanding reports of promising results (McAllister et al 2009;Syedain et al 2017;Kirkton et al 2019), cell-based strategies remain limited by the absence of protocols for the rapid and scalable production of patient-specific vascular wall cells and need for decellularization before implantation (Wystrychowski et al 2014;Lawson et al 2016). More specifically, studies have revealed feasibility challenges when using cells isolated from the intended patient population (>65 years old), or allogeneic sources, including reduced proliferation and ECM production due to telomere shortening (Poh et al 2005), and immune rejection associated with HLA mismatching.…”