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

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.

Susceptibility of ePTFE vascular grafts and bioengineered human acellular vessels to infection.

BACKGROUND: Synthetic expanded polytetrafluorethylene (ePTFE) grafts are routinely used for vascular repair and reconstruction but prone to sustained bacterial infections. Investigational bioengineered human acellular vessels (HAVs) have shown clinical success and may confer lower susceptibility to infection. Here we directly compared the susceptibility of ePTFE grafts and HAV to bacterial contamination in a preclinical model of infection. MATERIALS AND METHODS: Sections (1 cm2) of ePTFE (n = 42) or HAV (n = 42) were inserted within bilateral subcutaneous pockets on the dorsum of rats and inoculated with Staphylococcus aureus (107 CFU/0.25 mL) or Escherichia coli (108 CFU/0.25 mL) before wound closure. Two weeks later, the implant sites were scored for abscess formation and explanted materials were halved for quantification of microbial recovery and histological analyses. RESULTS: The ePTFE implants had significantly higher abscess formation scores for both S. aureus and E. coli inoculations compared to that of HAV. In addition, significantly more bacteria were recovered from explanted ePTFE compared to HAV. Gram staining of explanted tissue sections revealed interstitial bacterial contamination within ePTFE, whereas no bacteria were identified in HAV tissue sections. Numerous CD45+ leukocytes, predominantly neutrophils, were found surrounding the ePTFE implants but minimal intact neutrophils were observed within the ePTFE matrix. The host cells surrounding and infiltrating the HAV explants were primarily nonleukocytes (CD45-). CONCLUSIONS: In an established animal model of infection, HAV was significantly less susceptible to bacterial colonization and abscess formation than ePTFE. The preclinical findings presented in this manuscript, combined with previously published clinical observations, suggest that bioengineered HAV may exhibit low rates of infection.

Ocular pathology of uncommon hematologic malignancies: a case series.

INTRODUCTION: In general, ocular complications of hematologic malignancies such as leukemia are well documented. However, reports of ocular involvement in such diseases as lymphomatoid granulomatosis and chronic myelomonocytic leukemia are uncommon. Here we present cases of these two relatively rare hematologic malignancies demonstrating clinical and subclinical ocular involvement. CASE PRESENTATION: In the first case, a 54-year-old man with a previous diagnosis of lymphomatoid granulomatosis presented with a new-onset conjunctival lesion while his systemic disease was thought to be in remission. A biopsy was taken that revealed heavy infiltrates of B and T cells at the site of the lesion. Molecular analysis confirmed that these cells were positive for both Epstein-Barr viral DNA and immunoglobulin heavy chain gene rearrangement, consistent with a manifestation of his systemic disease. In the second case, a 51-year-old man with chronic myelomonocytic leukemia died after a waxing and waning clinical course. Post-mortem studies revealed the presence of atypical monocytes in the choroidal and subretinal spaces, consistent with his previous diagnosis. CONCLUSION: While ocular involvement in hematologic malignancies is not uncommon, these two cases describe involvement of the eye by two relatively rare neoplasms. We herein emphasize novel findings in each case, including conjunctival involvement as the first sign of recurrent lymphomatoid granulomatosis and the combination of subretinal and choroidal myelomonocytic leukemic infiltration. With the evolution of new antineoplastic therapies that may prolong life, these cases exemplify the importance of eye care in patients diagnosed with hematologic malignancies.